| 1. |
- Elsik, Christine G., et al.
(författare)
-
The Genome Sequence of Taurine Cattle : A Window to Ruminant Biology and Evolution
- 2009
-
Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 324:5926, s. 522-528
-
Tidskriftsartikel (refereegranskat)abstract
- To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
|
|
| 2. |
- Ademuyiwa, Adesoji O., et al.
(författare)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
Ingår i: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 3. |
- Fresard, Laure, et al.
(författare)
-
Identification of rare-disease genes using blood transcriptome sequencing and large control cohorts
- 2019
-
Ingår i: Nature Medicine. - : NATURE PUBLISHING GROUP. - 1078-8956 .- 1546-170X. ; 25:6, s. 911-919
-
Tidskriftsartikel (refereegranskat)abstract
- It is estimated that 350 million individuals worldwide suffer from rare diseases, which are predominantly caused by mutation in a single gene(1). The current molecular diagnostic rate is estimated at 50%, with whole-exome sequencing (WES) among the most successful approaches(2-5). For patients in whom WES is uninformative, RNA sequencing (RNA-seq) has shown diagnostic utility in specific tissues and diseases(6-8). This includes muscle biopsies from patients with undiagnosed rare muscle disorders(6,9), and cultured fibroblasts from patients with mitochondrial disorders(7). However, for many individuals, biopsies are not performed for clinical care, and tissues are difficult to access. We sought to assess the utility of RNA-seq from blood as a diagnostic tool for rare diseases of different pathophysiologies. We generated whole-blood RNA-seq from 94 individuals with undiagnosed rare diseases spanning 16 diverse disease categories. We developed a robust approach to compare data from these individuals with large sets of RNA-seq data for controls (n = 1,594 unrelated controls and n = 49 family members) and demonstrated the impacts of expression, splicing, gene and variant filtering strategies on disease gene identification. Across our cohort, we observed that RNA-seq yields a 7.5% diagnostic rate, and an additional 16.7% with improved candidate gene resolution.
|
|
| 4. |
- Palmer, Nicholette D, et al.
(författare)
-
A genome-wide association search for type 2 diabetes genes in African Americans.
- 2012
-
Ingår i: PloS one. - San Francisco : Public Library of Science (PLoS). - 1932-6203. ; 7:1, s. e29202-
-
Tidskriftsartikel (refereegranskat)abstract
- African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
|
|
| 5. |
- Birney, Ewan, et al.
(författare)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
Tidskriftsartikel (refereegranskat)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
|
|
| 6. |
|
|
| 7. |
- Weinstein, John N., et al.
(författare)
-
The cancer genome atlas pan-cancer analysis project
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:10, s. 1113-1120
-
Forskningsöversikt (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) Research Network has profiled and analyzed large numbers of human tumors to discover molecular aberrations at the DNA, RNA, protein and epigenetic levels. The resulting rich data provide a major opportunity to develop an integrated picture of commonalities, differences and emergent themes across tumor lineages. The Pan-Cancer initiative compares the first 12 tumor types profiled by TCGA. Analysis of the molecular aberrations and their functional roles across tumor types will teach us how to extend therapies effective in one cancer type to others with a similar genomic profile. © 2013 Nature America, Inc. All rights reserved.
|
|
| 8. |
- Willer, Cristen J., et al.
(författare)
-
Six new loci associated with body mass index highlight a neuronal influence on body weight regulation
- 2009
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:1, s. 25-34
-
Tidskriftsartikel (refereegranskat)abstract
- Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 x 10(-8)): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
|
|
| 9. |
- Bailey, Matthew H., et al.
(författare)
-
Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.
|
|
| 10. |
- Bouchard, Claude, et al.
(författare)
-
Personalized Preventive Medicine : Genetics and the Response to Regular Exercise in Preventive Interventions
- 2015
-
Ingår i: Progress in cardiovascular diseases. - : Elsevier BV. - 0033-0620 .- 1873-1740. ; 57:4, s. 337-346
-
Tidskriftsartikel (refereegranskat)abstract
- Regular exercise and a physically active lifestyle have favorable effects on health. Several issues related to this theme are addressed in this report. A comment on the requirements of personalized exercise medicine and in-depth biological profiling along with the opportunities that they offer is presented. This is followed by a brief overview of the evidence for the contributions of genetic differences to the ability to benefit from regular exercise. Subsequently, studies showing that mutations in TP53 influence exercise capacity in mice and humans are succinctly described. The evidence for effects of exercise on endothelial function in health and disease also is covered. Finally, changes in cardiac and skeletal muscle in response to exercise and their implications for patients with cardiac disease are summarized. Innovative research strategies are needed to define the molecular mechanisms involved in adaptation to exercise and to translate them into useful clinical and public health applications.
|
|
| 11. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
|
|
| 12. |
- Chu, Matthew R., et al.
(författare)
-
An imaging polarimetry survey of Type Ia supernovae : are peculiar extinction and polarization properties produced by circumstellar or interstellar matter?
- 2022
-
Ingår i: Monthly notices of the Royal Astronomical Society. - : Oxford University Press (OUP). - 0035-8711 .- 1365-2966. ; 509:4, s. 6028-6046
-
Tidskriftsartikel (refereegranskat)abstract
- Some highly reddened Type Ia supernovae (SNe Ia) display low total-to-selective extinction ratios (RV ≲ 2) in comparison to that of typical Milky Way dust (RV ≈ 3.3), and polarization curves that rise steeply to blue wavelengths, with peak polarization values at short wavelengths (λmax<0.4μ) in comparison to the typical Galactic values (λmax≈0.55μ m). Understanding the source of these properties could provide insight into the progenitor systems of SNe Ia. We aim to determine whether they are the result of the host galaxy’s interstellar dust or circumstellar dust. This is accomplished by analysing the continuum polarization of 66 SNe Ia in dust-rich spiral galaxies and 13 SNe Ia in dust-poor elliptical galaxies as a function of normalized galactocentric distance. We find that there is a general trend of SNe Ia in spiral galaxies displaying increased polarization values when located closer to the host galaxies’ centre, while SNe Ia in elliptical host galaxies display low polarization. Furthermore, all highly polarized SNe Ia in spiral host galaxies display polarization curves rising toward blue wavelengths, while no evidence of such polarization properties is shown in elliptical host galaxies. This indicates that the source of the peculiar polarization curves is likely the result of interstellar material as opposed to circumstellar material. The peculiar polarization and extinction properties observed toward some SNe Ia may be explained by the radiative torque disruption mechanism induced by the SN or the interstellar radiation field.
|
|
| 13. |
- Ding, Li, et al.
(författare)
-
Somatic mutations affect key pathways in lung adenocarcinoma
- 2008
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 455:7216, s. 1069-1075
-
Tidskriftsartikel (refereegranskat)abstract
- Determining the genetic basis of cancer requires comprehensive analyses of large collections of histopathologically well-classified primary tumours. Here we report the results of a collaborative study to discover somatic mutations in 188 human lung adenocarcinomas. DNA sequencing of 623 genes with known or potential relationships to cancer revealed more than 1,000 somatic mutations across the samples. Our analysis identified 26 genes that are mutated at significantly high frequencies and thus are probably involved in carcinogenesis. The frequently mutated genes include tyrosine kinases, among them the EGFR homologue ERBB4; multiple ephrin receptor genes, notably EPHA3; vascular endothelial growth factor receptor KDR; and NTRK genes. These data provide evidence of somatic mutations in primary lung adenocarcinoma for several tumour suppressor genes involved in other cancers--including NF1, APC, RB1 and ATM--and for sequence changes in PTPRD as well as the frequently deleted gene LRP1B. The observed mutational profiles correlate with clinical features, smoking status and DNA repair defects. These results are reinforced by data integration including single nucleotide polymorphism array and gene expression array. Our findings shed further light on several important signalling pathways involved in lung adenocarcinoma, and suggest new molecular targets for treatment.
|
|
| 14. |
- Goobar, Ariel, 1962-, et al.
(författare)
-
Uncovering a population of gravitational lens galaxies with magnified standard candle SN Zwicky
- 2023
-
Ingår i: Nature Astronomy. - 2397-3366. ; 7:9, s. 1098-1107
-
Tidskriftsartikel (refereegranskat)abstract
- Detecting gravitationally lensed supernovae is among the biggest challenges in astronomy. It involves a combination of two very rare phenomena: catching the transient signal of a stellar explosion in a distant galaxy and observing it through a nearly perfectly aligned foreground galaxy that deflects light towards the observer. Here we describe how high-cadence optical observations with the Zwicky Transient Facility, with its unparalleled large field of view, led to the detection of a multiply imaged type Ia supernova, SN Zwicky, also known as SN 2022qmx. Magnified nearly 25-fold, the system was found thanks to the standard candle nature of type Ia supernovae. High-spatial-resolution imaging with the Keck telescope resolved four images of the supernova with very small angular separation, corresponding to an Einstein radius of only θE = 0.167″ and almost identical arrival times. The small θE and faintness of the lensing galaxy are very unusual, highlighting the importance of supernovae to fully characterize the properties of galaxy-scale gravitational lenses, including the impact of galaxy substructures.
|
|
| 15. |
- Heid, Iris M, et al.
(författare)
-
Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 949-960
-
Tidskriftsartikel (refereegranskat)abstract
- Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻¹³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.
|
|
| 16. |
- Hudson, Thomas J., et al.
(författare)
-
International network of cancer genome projects
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
-
Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
|
|
| 17. |
|
|
| 18. |
- James, Matthew T, et al.
(författare)
-
A Meta-analysis of the Association of Estimated GFR, Albuminuria, Diabetes Mellitus, and Hypertension With Acute Kidney Injury.
- 2015
-
Ingår i: American Journal of Kidney Diseases. - : Elsevier BV. - 0272-6386 .- 1523-6838. ; 66:4, s. 602-612
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Diabetes mellitus and hypertension are risk factors for acute kidney injury (AKI). Whether estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (ACR) remain risk factors for AKI in the presence and absence of these conditions is uncertain.STUDY DESIGN: Meta-analysis of cohort studies.SETTING & POPULATION: 8 general-population (1,285,045 participants) and 5 chronic kidney disease (CKD; 79,519 participants) cohorts.SELECTION CRITERIA FOR STUDIES: Cohorts participating in the CKD Prognosis Consortium.PREDICTORS: Diabetes and hypertension status, eGFR by the 2009 CKD Epidemiology Collaboration creatinine equation, urine ACR, and interactions.OUTCOME: Hospitalization with AKI, using Cox proportional hazards models to estimate HRs of AKI and random-effects meta-analysis to pool results.RESULTS: During a mean follow-up of 4 years, there were 16,480 episodes of AKI in the general-population and 2,087 episodes in the CKD cohorts. Low eGFRs and high ACRs were associated with higher risks of AKI in individuals with or without diabetes and with or without hypertension. When compared to a common reference of eGFR of 80mL/min/1.73m(2) in nondiabetic patients, HRs for AKI were generally higher in diabetic patients at any level of eGFR. The same was true for diabetic patients at all levels of ACR compared with nondiabetic patients. The risk gradient for AKI with lower eGFRs was greater in those without diabetes than with diabetes, but similar with higher ACRs in those without versus with diabetes. Those with hypertension had a higher risk of AKI at eGFRs>60mL/min/1.73m(2) than those without hypertension. However, risk gradients for AKI with both lower eGFRs and higher ACRs were greater for those without than with hypertension.LIMITATIONS: AKI identified by diagnostic code.CONCLUSIONS: Lower eGFRs and higher ACRs are associated with higher risks of AKI among individuals with or without either diabetes or hypertension.
|
|
| 19. |
- Karlsson, Linn, et al.
(författare)
-
Physical and Chemical Properties of Cloud Droplet Residuals and Aerosol Particles During the Arctic Ocean 2018 Expedition
- 2022
-
Ingår i: Journal of Geophysical Research - Atmospheres. - 2169-897X .- 2169-8996. ; 127:11
-
Tidskriftsartikel (refereegranskat)abstract
- Detailed knowledge of the physical and chemical properties and sources of particles that form clouds is especially important in pristine areas like the Arctic, where particle concentrations are often low and observations are sparse. Here, we present in situ cloud and aerosol measurements from the central Arctic Ocean in August–September 2018 combined with air parcel source analysis. We provide direct experimental evidence that Aitken mode particles (particles with diameters ≲70 nm) significantly contribute to cloud condensation nuclei (CCN) or cloud droplet residuals, especially after the freeze-up of the sea ice in the transition toward fall. These Aitken mode particles were associated with air that spent more time over the pack ice, while size distributions dominated by accumulation mode particles (particles with diameters ≳70 nm) showed a stronger contribution of oceanic air and slightly different source regions. This was accompanied by changes in the average chemical composition of the accumulation mode aerosol with an increased relative contribution of organic material toward fall. Addition of aerosol mass due to aqueous-phase chemistry during in-cloud processing was probably small over the pack ice given the fact that we observed very similar particle size distributions in both the whole-air and cloud droplet residual data. These aerosol–cloud interaction observations provide valuable insight into the origin and physical and chemical properties of CCN over the pristine central Arctic Ocean.
|
|
| 20. |
|
|
| 21. |
- Kurganskiy, Alexander, et al.
(författare)
-
Predicting the severity of the grass pollen season and the effect of climate change in Northwest Europe
- 2021
-
Ingår i: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 7:13
-
Tidskriftsartikel (refereegranskat)abstract
- Allergic rhinitis is an inflammation in the nose caused by overreaction of the immune system to allergens in the air. Managing allergic rhinitis symptoms is challenging and requires timely intervention. The following are major questions often posed by those with allergic rhinitis: How should I prepare for the forthcoming season? How will the season's severity develop over the years? No country yet provides clear guidance addressing these questions. We propose two previously unexplored approaches for forecasting the severity of the grass pollen season on the basis of statistical and mechanistic models. The results suggest annual severity is largely governed by preseasonal meteorological conditions. The mechanistic model suggests climate change will increase the season severity by up to 60%, in line with experimental chamber studies. These models can be used as forecasting tools for advising individuals with hay fever and health care professionals how to prepare for the grass pollen season.
|
|
| 22. |
- Lango Allen, Hana, et al.
(författare)
-
Hundreds of variants clustered in genomic loci and biological pathways affect human height.
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 467:7317, s. 832-8
-
Tidskriftsartikel (refereegranskat)abstract
- Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P<0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.
|
|
| 23. |
- Maitre, Léa, et al.
(författare)
-
State-of-the-art methods for exposure-health studies: Results from the exposome data challenge event
- 2022
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 168
-
Tidskriftsartikel (refereegranskat)abstract
- The exposome recognizes that individuals are exposed simultaneously to a multitude of different environmental factors and takes a holistic approach to the discovery of etiological factors for disease. However, challenges arise when trying to quantify the health effects of complex exposure mixtures. Analytical challenges include dealing with high dimensionality, studying the combined effects of these exposures and their interactions, integrating causal pathways, and integrating high-throughput omics layers. To tackle these challenges, the Barcelona Institute for Global Health (ISGlobal) held a data challenge event open to researchers from all over the world and from all expertises. Analysts had a chance to compete and apply state-of-the-art methods on a common partially simulated exposome dataset (based on real case data from the HELIX project) with multiple correlated exposure variables (P > 100 exposure variables) arising from general and personal environments at different time points, biological molecular data (multi-omics: DNA methylation, gene expression, proteins, metabolomics) and multiple clinical phenotypes in 1301 mother–child pairs. Most of the methods presented included feature selection or feature reduction to deal with the high dimensionality of the exposome dataset. Several approaches explicitly searched for combined effects of exposures and/or their interactions using linear index models or response surface methods, including Bayesian methods. Other methods dealt with the multi-omics dataset in mediation analyses using multiple-step approaches. Here we discuss features of the statistical models used and provide the data and codes used, so that analysts have examples of implementation and can learn how to use these methods. Overall, the exposome data challenge presented a unique opportunity for researchers from different disciplines to create and share state-of-the-art analytical methods, setting a new standard for open science in the exposome and environmental health field.
|
|
| 24. |
- Margulies, Elliott H, et al.
(författare)
-
Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
-
Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
-
Tidskriftsartikel (refereegranskat)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
|
|
| 25. |
- Mattsson, C. Mikael, et al.
(författare)
-
Informing women’s cardiovascular health through genomic analysis of extreme endurance athletes
- 2015
-
Konferensbidrag (refereegranskat)abstract
- Cardiovascular health exists as a spectrum of wellness and disease states. We hypothesize that interrogating the tail ends of the distribution for individuals with extreme phenotypes, such as high VO2max in endurance athletes, will inform prevention, cause and treatment of pathogenic conditions. Mounting literature suggests that the physiological path to athletic performance is different among males and females. Traits with published sexual dichotomy include lactate threshold, efficiency, heat management, and fat metabolism. To define the genetic roots of this dichotomy, we propose to investigate sex-specific genetic determinants of VO2max among elite endurance athletes. We have recruited 36 female (VO2max>63 ml/kg; >99.99th percentile) and 129 male (>75 ml/kg) elite athletes (n=167) who have been consented and undergone enhanced whole exome sequencing. Even with differential eligibility, skewed recruitment (1:3.5) is a challenge. We will recruit a total of 100 female and 156 male elite athletes, and analyze these 256 exomes for burden of rare genetic variation that may impact sex-specific determinants of VO2max. We will combine these data with an additional 1850 samples of elite athletes to evaluate for common variants that have sex-specific effects on VO2max. Lastly, we will do a sex specific genetic cohort comparison of endurance athletes with existing collections of cardiovascular disease patients. Our preliminary results show tantalizing evidence for several highly plausible sex specific genes, including androgen receptor (AR) and FTO. The AR is the target of several known performance enhancing drugs, such as testosterone. FTO is associated with numerous aspects of body composition, energy management and even some evidence for age of menarche. While already promising, rigorous analysis, increased sample size and orthogonal replication is required as our next step.
|
|
| 26. |
- Mattsson, C. Mikael, et al.
(författare)
-
Sports genetics moving forward - lessons learned from medical research
- 2016
-
Ingår i: Physiological Genomics. - : American Physiological Society. - 1094-8341 .- 1531-2267. ; 48:3, s. 175-182
-
Tidskriftsartikel (refereegranskat)abstract
- Sports genetics can take advantage of lessons learned from human disease genetics. By righting past mistakes and increasing scientific rigor, the breadth and depth of knowledge in the field can be magnified. We present an outline of challenges facing sports genetics in the light of experiences from medical research.Sports performance is complex, resulting from a combination of a wide variety of different traits and attributes. Improving sports genetics will foremost require analyses based on detailed phenotyping. In order to find widely valid, reproducible common variants associated with athletic phenotypes, study sample sizes must be dramatically increased. One paradox is that in order to confirm relevance, replications in specific populations must be undertaken. Family studies of athletes may facilitate the discovery of rare variants with large effects on athletic phenotypes. The complexity of the human genome, combined with the complexity of athletic phenotypes, will require additional metadata and biological validation to identify a comprehensive set of genes involved.Analysis of personal genetic and multiomic profiles contribute to our conceptualization of precision medicine; the same will be the case in precision sports science. In the refinement of sports genetics it is essential to evaluate similarities and differences between genders and among ethnicities. Sports genetics to date have been hampered by small sample sizes and biased methodology which can lead to erroneous associations and overestimation of effect sizes. Consequently, currently available genetic tests based on these inherently limited data cannot predict athletic performance with any accuracy.
|
|
| 27. |
- Mattsson, C. Mikael, et al.
(författare)
-
The ELITE project (Exercise at the Limit - Inherited Traits of Endurance) - the genetic profiles of the best endurance athletes in the world.
- 2017
-
Konferensbidrag (refereegranskat)abstract
- Cardiovascular health exists as a spectrum of wellness and disease states. Moreover, a significant portion of what defines these states is due to genetics. We hypothesize that there exist genes and pathways that dually contribute to both disease and extreme health states. Interrogating the ‘adaptive’ tail of the distribution for individuals with extreme phenotypes, such as high maximum oxygen uptake (VO2max) in endurance athletes, will inform prevention, cause and treatment of pathogenic (‘maladaptive’) conditions. 1 To date, most genetic studies in the athlete population have examined a subset of genes (out of more than 21,000 in the genome), using small sample sizes and qualitative measures of performance. To the best of our knowledge, there has not been a comprehensive genetic study of endurance athletes with strict quantitative eligibility criteria.2-4The ELITE project (Exercise at the Limit – Inherited Traits of Endurance) intends to investigate the world’s best endurance athletes, i.e. individuals with extremely high VO2max. A primary goal is to determine what role genetic variation plays in athletic ability. One of the ancillary goals of the project is to understand the unique genetic differences contributing to extreme fitness in women versus men. We will sequence and analyze the genomes of elite level competitive athletes from various countries (including USA, Scandinavia, UK, Japan, and Brazil) who are highly successful in one of several endurance sports (such as running, cross country skiing, triathlon, cycling, rowing). We have recruited 750 elite athletes (142 women and 608 men) who have been consented and undergone enhanced whole exome sequencing and/or MEGA chip GWAS analysis. Inclusion criteria for the study restricts to the highest tail end (>99.98th percentile or 1/5000), i.e. VO2max >63 ml/kg for women and >75 ml/kg for men. Even with differential eligibility, skewed recruitment (1:4) is a challenge.Our preliminary results show tantalizing evidence for potentially beneficial genetic variants in several highly plausible genes. Additionally, pilot burden testing on a subset of the athletes also showed promising results. While already promising, rigorous analysis, increased sample size and orthogonal replication is required as our next step. Mattsson CM, Wheeler M, Waggott D, Caleshu C, Ashley EA. Sports genetics moving forward - lessons learned from medical research. Physiol Genomics. 2016; 48(3):175-182.Bouchard C, Sarzynski MA, Rice TK, Kraus WE, Church TS, Sung YJ, Rao DC, Rankinen T. Genomic predictors of the maximal O₂ uptake response to standardized exercise training programs. J Appl Physiol (1985). 2011; 110(5):1160-70.Eynon N, Morán M, Birk R, Lucia A. The champions' mitochondria: is it genetically determined? A review on mitochondrial DNA and elite athletic performance. Physiol Genomics. 2011;43(13):789-98.Pitsiladis YP, Tanaka M, Eynon N, Bouchard C, North KN, Williams AG, Collins M, Moran CN, Britton SL, Fuku N, Ashley EA, Klissouras V, Lucia A, Ahmetov II, de Geus E, Alsayrafi M; Athlome Project Consortium. Athlome Project Consortium: a concerted effort to discover genomic and other "omic" markers of athletic performance. Physiol Genomics. 2016;48(3):183-90.
|
|
| 28. |
- Moneghetti, Kegan James, et al.
(författare)
-
Echocardiographic Assessment of Left Ventricular Remodeling in American Style Footballers
- 2019
-
Ingår i: International Journal of Sports Medicine. - : Georg Thieme Verlag KG. - 0172-4622 .- 1439-3964. ; 41:01, s. 27-35
-
Tidskriftsartikel (refereegranskat)abstract
- AbstractSeveral athletic programs incorporate echocardiography during pre-participation screening of American Style Football (ASF) players with great variability in reported echocardiographic values. Pre-participation screening was performed in National Collegiate Athletic Association Division I ASF players from 2008 to 2016 at the Division of Sports Cardiology. The echocardiographic protocol focused on left ventricular (LV) mass, mass-to-volume ratio, sphericity, ejection fraction, and longitudinal Lagrangian strain. LV mass was calculated using the area-length method in end-diastole and end-systole. A total of two hundred and thirty players were included (18±1 years, 57% were Caucasian, body mass index 29±4 kg/m2) after four players (2%) were excluded for pathological findings. Although there was no difference in indexed LV mass by race (Caucasian 78±11 vs. African American 81±10 g/m2, p=0.089) or sphericity (Caucasian 1.81±0.13 vs. African American 1.78±0.14, p=0.130), the mass-to-volume ratio was higher in African Americans (0.91±0.09 vs. 0.83±0.08, p<0.001). No race-specific differences were noted in LV longitudinal Lagrangian strain. Player position appeared to have a limited role in defining LV remodeling. In conclusion, significant echocardiographic differences were observed in mass-to-volume ratio between African American and Caucasian players. These demographics should be considered as part of pre-participation screening.
|
|
| 29. |
- Patti, Alessandro, et al.
(författare)
-
Respiratory gas kinetics in patients with congestive heart failure during recovery from peak exercise
- 2023
-
Ingår i: Clinics. - : ELSEVIER ESPANA. - 1807-5932 .- 1980-5322. ; 78
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Cardiopulmonary Exercise Testing (CPX) is essential for the assessment of exercise capacity for patients with Chronic Heart Failure (CHF). Respiratory gas and hemodynamic parameters such as Ventilatory Efficiency (VE/VCO2 slope), peak oxygen uptake (peak VO2), and heart rate recovery are established diagnostic and prognostic markers for clinical populations. Previous studies have suggested the clinical value of metrics related to respiratory gas collected during recovery from peak exercise, particularly recovery time to 50% (T1/2) of peak VO2. The current study explores these metrics in detail during recovery from peak exercise in CHF.Methods: Patients with CHF who were referred for CPX and healthy individuals without formal diagnoses were assessed for inclusion. All subjects performed CPX on cycle ergometers to volitional exhaustion and were monitored for at least five minutes of recovery. CPX data were analyzed for overshoot of respiratory exchange ratio (RER=VCO2/VO2), ventilatory equivalent for oxygen (VE/VO2), end-tidal partial pressure of oxygen (PETO2), and T1/2 of peak VO2 and VCO2.Results: Thirty-two patients with CHF and 30 controls were included. Peak VO2 differed significantly between patients and controls (13.5 & PLUSMN; 3.8 vs. 32.5 & PLUSMN; 9.8 mL/Kg*min-1, p < 0.001). Mean Left Ventricular Ejection Fraction (LVEF) was 35.9 & PLUSMN; 9.8% for patients with CHF compared to 61.1 & PLUSMN; 8.2% in the control group. The T1/2 of VO2, VCO2 and VE was significantly higher in patients (111.3 & PLUSMN; 51.0, 132.0 & PLUSMN; 38.8 and 155.6 & PLUSMN; 45.5s) than in controls (58.08 & PLUSMN; 13.2, 74.3 & PLUSMN; 21.1, 96.7 & PLUSMN; 36.8s; p < 0.001) while the overshoot of PETO2, VE/VO2 and RER was significantly lower in patients (7.2 & PLUSMN; 3.3, 41.9 & PLUSMN; 29.1 and 25.0 & PLUSMN; 13.6%) than in controls (10.1 & PLUSMN; 4.6, 62.1 & PLUSMN; 17.7 and 38.7 & PLUSMN; 15.1%; all p < 0.01). Most of the recovery metrics were significantly correlated with peak VO2 in CHF patients, but not with LVEF.Conclusions: Patients with CHF have a significantly blunted recovery from peak exercise. This is reflected in delays of VO2, VCO2, VE, PETO2, RER and VE/VO2, reflecting a greater energy required to return to baseline. Abnormal respiratory gas kinetics in CHF was negatively correlated with peak VO2 but not baseline LVEF.
|
|
| 30. |
- Reyna, Matthew A, et al.
(författare)
-
Pathway and network analysis of more than 2500 whole cancer genomes
- 2020
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- The catalog of cancer driver mutations in protein-coding genes has greatly expanded in the past decade. However, non-coding cancer driver mutations are less well-characterized and only a handful of recurrent non-coding mutations, most notably TERT promoter mutations, have been reported. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancer across 38 tumor types, we perform multi-faceted pathway and network analyses of non-coding mutations across 2583 whole cancer genomes from 27 tumor types compiled by the ICGC/TCGA PCAWG project that was motivated by the success of pathway and network analyses in prioritizing rare mutations in protein-coding genes. While few non-coding genomic elements are recurrently mutated in this cohort, we identify 93 genes harboring non-coding mutations that cluster into several modules of interacting proteins. Among these are promoter mutations associated with reduced mRNA expression in TP53, TLE4, and TCF4. We find that biological processes had variable proportions of coding and non-coding mutations, with chromatin remodeling and proliferation pathways altered primarily by coding mutations, while developmental pathways, including Wnt and Notch, altered by both coding and non-coding mutations. RNA splicing is primarily altered by non-coding mutations in this cohort, and samples containing non-coding mutations in well-known RNA splicing factors exhibit similar gene expression signatures as samples with coding mutations in these genes. These analyses contribute a new repertoire of possible cancer genes and mechanisms that are altered by non-coding mutations and offer insights into additional cancer vulnerabilities that can be investigated for potential therapeutic treatments.
|
|
| 31. |
- Rowney, Francis M, et al.
(författare)
-
Environmental DNA reveals links between abundance and composition of airborne grass pollen and respiratory health
- 2021
-
Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 31:9, s. 4-2003
-
Tidskriftsartikel (refereegranskat)abstract
- Grass (Poaceae) pollen is the most important outdoor aeroallergen,1 exacerbating a range of respiratory conditions, including allergic asthma and rhinitis ("hay fever").2-5 Understanding the relationships between respiratory diseases and airborne grass pollen with a view to improving forecasting has broad public health and socioeconomic relevance. It is estimated that there are over 400 million people with allergic rhinitis6 and over 300 million with asthma, globally,7 often comorbidly.8 In the UK, allergic asthma has an annual cost of around US$ 2.8 billion (2017).9 The relative contributions of the >11,000 (worldwide) grass species (C. Osborne et al., 2011, Botany Conference, abstract) to respiratory health have been unresolved,10 as grass pollen cannot be readily discriminated using standard microscopy.11 Instead, here we used novel environmental DNA (eDNA) sampling and qPCR12-15 to measure the relative abundances of airborne pollen from common grass species during two grass pollen seasons (2016 and 2017) across the UK. We quantitatively demonstrate discrete spatiotemporal patterns in airborne grass pollen assemblages. Using a series of generalized additive models (GAMs), we explore the relationship between the incidences of airborne pollen and severe asthma exacerbations (sub-weekly) and prescribing rates of drugs for respiratory allergies (monthly). Our results indicate that a subset of grass species may have disproportionate influence on these population-scale respiratory health responses during peak grass pollen concentrations. The work demonstrates the need for sensitive and detailed biomonitoring of harmful aeroallergens in order to investigate and mitigate their impacts on human health.
|
|
| 32. |
- Sako, Masao, et al.
(författare)
-
The Data Release of the Sloan Digital Sky Survey-II Supernova Survey
- 2018
-
Ingår i: Publications of the Astronomical Society of the Pacific. - : IOP Publishing. - 0004-6280 .- 1538-3873. ; 130:988
-
Tidskriftsartikel (refereegranskat)abstract
- This paper describes the data release of the Sloan Digital Sky Survey-II (SDSS-II) Supernova Survey conducted between 2005 and 2007. Light curves, spectra, classifications, and ancillary data are presented for 10,258 variable and transient sources discovered through repeat ugriz imaging of SDSS Stripe 82, a 300 deg(2) area along the celestial equator. This data release is comprised of all transient sources brighter than r similar or equal to 22.5 mag with no history of variability prior to 2004. Dedicated spectroscopic observations were performed on a subset of 889 transients, as well as spectra for thousands of transient host galaxies using the SDSS-III BOSS spectrographs. Photometric classifications are provided for the candidates with good multi-color light curves that were not observed spectroscopically, using host galaxy redshift information when available. From these observations, 4607 transients are either spectroscopically confirmed, or likely to be, supernovae, making this the largest sample of supernova candidates ever compiled. We present a new method for SN host-galaxy identification and derive host-galaxy properties including stellar masses, star formation rates, and the average stellar population ages from our SDSS multi-band photometry. We derive SALT2 distance moduli for a total of 1364 SN. Ia with spectroscopic redshifts as well as photometric redshifts for a further 624 purely photometric SN. Ia candidates. Using the spectroscopically confirmed subset of the three-year SDSS-II SN. Ia sample and assuming a flat.CDM cosmology, we determine Omega(M) = 0.315 +/- 0.093 (statistical error only) and detect a non-zero cosmological constant at 5.7 sigma.
|
|
| 33. |
- Shcherbina, Anna, et al.
(författare)
-
Accuracy in Wrist-Worn, Sensor-Based Measurements of Heart Rate and Energy Expenditure in a Diverse Cohort.
- 2017
-
Ingår i: Journal of Personalized Medicine. - : MDPI AG. - 2075-4426. ; 7:2
-
Tidskriftsartikel (refereegranskat)abstract
- The ability to measure physical activity through wrist-worn devices provides an opportunity for cardiovascular medicine. However, the accuracy of commercial devices is largely unknown. The aim of this work is to assess the accuracy of seven commercially available wrist-worn devices in estimating heart rate (HR) and energy expenditure (EE) and to propose a wearable sensor evaluation framework. We evaluated the Apple Watch, Basis Peak, Fitbit Surge, Microsoft Band, Mio Alpha 2, PulseOn, and Samsung Gear S2. Participants wore devices while being simultaneously assessed with continuous telemetry and indirect calorimetry while sitting, walking, running, and cycling. Sixty volunteers (29 male, 31 female, age 38 ± 11 years) of diverse age, height, weight, skin tone, and fitness level were selected. Error in HR and EE was computed for each subject/device/activity combination. Devices reported the lowest error for cycling and the highest for walking. Device error was higher for males, greater body mass index, darker skin tone, and walking. Six of the devices achieved a median error for HR below 5% during cycling. No device achieved an error in EE below 20 percent. The Apple Watch achieved the lowest overall error in both HR and EE, while the Samsung Gear S2 reported the highest. In conclusion, most wrist-worn devices adequately measure HR in laboratory-based activities, but poorly estimate EE, suggesting caution in the use of EE measurements as part of health improvement programs. We propose reference standards for the validation of consumer health devices (http://precision.stanford.edu/).
|
|
| 34. |
- Shcherbina, Anna, et al.
(författare)
-
Accuracy in wrist-worn, sensor-based measurements of heart rate and energy expenditure in a diverse cohort
- 2016
-
Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Background: The ability to measure activity and physiology through wrist-worn devices provides an opportunity for cardiovascular medicine. However, the accuracy of commercial devices is largely unknown. Objective: To assess the accuracy of seven commercially available wrist-worn devices in estimating heart rate (HR) and energy expenditure (EE) and to propose a wearable sensor evaluation framework. Methods: We evaluated the Apple Watch, Basis Peak, Fitbit Surge, Microsoft Band, Mio Alpha 2, PulseOn, and Samsung Gear S2. Participants wore devices while being simultaneously assessed with continuous telemetry and indirect calorimetry while sitting, walking, running, and cycling. Sixty volunteers (29 male, 31 female, age 38 +/- 11 years) of diverse age, height, weight, skin tone, and fitness level were selected. Error in HR and EE was computed for each subject/device/activity combination. Results: Devices reported the lowest error for cycling and the highest for walking. Device error was higher for males, greater body mass index, darker skin tone, and walking. Six of the devices achieved a median error for HR below 5% during cycling. No device achieved an error in EE below 20 percent. The Apple Watch achieved the lowest overall error in both HR and EE, while the Samsung Gear S2 reported the highest. Conclusions: Most wrist-worn devices adequately measure HR in laboratory-based activities, but poorly estimate EE, suggesting caution in the use of EE measurements as part of health improvement programs. We propose reference standards for the validation of consumer health devices (http://precision.stanford.edu/).
|
|
| 35. |
- Speliotes, Elizabeth K., et al.
(författare)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
|
|
| 36. |
- Waggott, Daryl, et al.
(författare)
-
The Genomics of Extreme Athletes. The ELITE Study (Exercise at the Limit - Inherited Traits of Endurance).
- 2016
-
Konferensbidrag (refereegranskat)abstract
- Health exists as a spectrum from disease to some outlier physiological optimum. To date most molecular genetic research has focused on disease states and less on extreme health populations. We hypothesize that interrogating outlier elite endurance athletes, with strict physiological eligibility criteria, will inform cardiovascular research through the identification of complementary pathways and therapeutic targets. Eligibility criteria for the ELITE study required a lifetime VO2max, which measures maximal oxygen consumption during peak aerobic exercise, at a threshold estimated to be attainable in less than 1 in 50,000 people (men 80ml/kg/min; women 65ml/kg/min). VO2max is reported to have substantial genetic influence (h2~0.5) and is correlated with endurance sport performance along with work efficiency. Several well documented cases of athletic outliers have been tied to rare genetic variants including the Finnish cross country skier Mäntyranta (EPOR) and Priscilla Lopes-Schliep (LMNA). In the later, the same domain of the LMNA gene is related to rare forms of muscular dystrophy. Additionally, adaptive hypoxia variations have been identified in high altitude populations in Tibet (EPAS1), Andes and Ethiopia. To date we have sequenced 268 ELITE participants using clinically enhanced exomes and run 550 samples on high density multi-ethnic SNP chips. Preliminary analysis has focused on a combination of rare variant curation and common variation association. Rare variation curation included prioritization of LOF variants within candidate genes related to oxygen transport, muscle physiology and metabolism (i.e. PPARA, PPARGC1A, RYR2, ACTN3) and global gene screening using in silico weighted burden testing. Common variant association (the largest GWAS of its kind) has been used to support rare variant findings and identify non-coding and structural variant association signals. We believe that our methodology of combining rare LOF variants with common variation association in a population with extreme endurance physiology will systematically identify pleiotropic genes with both protective and pathogenic features similar to PCSK9.
|
|
| 37. |
- Zhao, Chaoyang, et al.
(författare)
-
A massive expansion of effector genes underlies gall-formation in the wheat pest Mayetiola destructor
- 2015
-
Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 25:5, s. 613-620
-
Tidskriftsartikel (refereegranskat)abstract
- Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood. We sequenced the genome of the Hessian fly (Mayetiola destructor; Diptera: Cecidomyiidae), a plant parasitic gall midge and a pest of wheat (Triticum spp.), with the aim of identifying genic modifications that contribute to its plant-parasitic lifestyle. Among several adaptive modifications, we discovered an expansive reservoir of potential effector proteins. Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. The largest known arthropod gene family (family SSGP-71) was also discovered within the effector reservoir. SSGP-71 proteins lack sequence homologies to other proteins, but their structures resemble both ubiquitin E3 ligases in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents responsible for arthropod-induced plant gall formation.
|
|
