| 1. |
- Felix, Janine F, et al.
(författare)
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Genome-wide association analysis identifies three new susceptibility loci for childhood body mass index.
- 2016
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 25:2, s. 389-403
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Tidskriftsartikel (refereegranskat)abstract
- A large number of genetic loci are associated with adult body mass index. However, the genetics of childhood body mass index are largely unknown. We performed a meta-analysis of genome-wide association studies of childhood body mass index, using sex- and age-adjusted standard deviation scores. We included 35 668 children from 20 studies in the discovery phase and 11 873 children from 13 studies in the replication phase. In total, 15 loci reached genome-wide significance (P-value < 5 × 10(-8)) in the joint discovery and replication analysis, of which 12 are previously identified loci in or close to ADCY3, GNPDA2, TMEM18, SEC16B, FAIM2, FTO, TFAP2B, TNNI3K, MC4R, GPR61, LMX1B and OLFM4 associated with adult body mass index or childhood obesity. We identified three novel loci: rs13253111 near ELP3, rs8092503 near RAB27B and rs13387838 near ADAM23. Per additional risk allele, body mass index increased 0.04 Standard Deviation Score (SDS) [Standard Error (SE) 0.007], 0.05 SDS (SE 0.008) and 0.14 SDS (SE 0.025), for rs13253111, rs8092503 and rs13387838, respectively. A genetic risk score combining all 15 SNPs showed that each additional average risk allele was associated with a 0.073 SDS (SE 0.011, P-value = 3.12 × 10(-10)) increase in childhood body mass index in a population of 1955 children. This risk score explained 2% of the variance in childhood body mass index. This study highlights the shared genetic background between childhood and adult body mass index and adds three novel loci. These loci likely represent age-related differences in strength of the associations with body mass index.
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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N = 1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Lapinlampi, Niina, et al.
(författare)
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Common data elements and data management : Remedy to cure underpowered preclinical studies
- 2017
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Ingår i: Epilepsy Research. - : Elsevier BV. - 0920-1211. ; 129, s. 87-90
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Tidskriftsartikel (refereegranskat)abstract
- Lack of translation of data obtained in preclinical trials to clinic has kindled researchers to develop new methodologies to increase the power and reproducibility of preclinical studies. One approach relates to harmonization of data collection and analysis, and has been used for a long time in clinical studies testing anti-seizure drugs. EPITARGET is a European Union FP7-funded research consortium composed of 18 partners from 9 countries. Its main research objective is to identify biomarkers and develop treatments for epileptogenesis. As the first step of harmonization of procedures between laboratories, EPITARGET established working groups for designing project-tailored common data elements (CDEs) and case report forms (CRFs) to be used in data collection and analysis. Eight major modules of CRFs were developed, presenting >1000 data points for each animal. EPITARGET presents the first single-project effort for harmonization of preclinical data collection and analysis in epilepsy research. EPITARGET is also anticipating the future challenges and requirements in a larger-scale preclinical harmonization of epilepsy studies, including training, data management expertise, cost, location, data safety and continuity of data repositories during and after funding period, and incentives motivating for the use of CDEs.
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| 4. |
- Liu, Xueping, et al.
(författare)
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Variants in the fetal genome near pro-inflammatory cytokine genes on 2q13 associate with gestational duration.
- 2019
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1
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Tidskriftsartikel (refereegranskat)abstract
- The duration of pregnancy is influenced by fetal and maternal genetic and non-genetic factors. Here we report a fetal genome-wide association meta-analysis of gestational duration, and early preterm, preterm, and postterm birth in 84,689 infants. One locus on chromosome 2q13 is associated with gestational duration; the association is replicated in 9,291 additional infants (combined P = 3.96 × 10-14). Analysis of 15,588 mother-child pairs shows that the association is driven by fetal rather than maternal genotype. Functional experiments show that the lead SNP, rs7594852, alters the binding of the HIC1 transcriptional repressor. Genes at the locus include several interleukin 1 family members with roles in pro-inflammatory pathways that are central to the process of parturition. Further understanding of the underlying mechanisms will be of great public health importance, since giving birth either before or after the window of term gestation is associated with increased morbidity and mortality.
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| 5. |
- Pitkänen, Timo P., et al.
(författare)
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Detecting subpixel deciduous components to complement traditional land cover classifications in Southwest Finland
- 2015
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Ingår i: International Journal of Applied Earth Observation and Geoinformation. - : Elsevier BV. - 1569-8432 .- 1872-826X. ; 42, s. 97-105
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Tidskriftsartikel (refereegranskat)abstract
- To ensure successful conservation of ecological and cultural landscape values, detailed and up-to-datespatial information of existing habitat patterns is essential. However, traditional satellite-based and rasterclassifications rely on pixels that are assigned to a single category and often generalized. For many frag-mented key habitats, such a strategy is too coarse and complementary data is needed. In this paper,we aim at detecting pixel-wise fractional coverage of broadleaved woodland and grassland componentsin a hemiboreal landscape. This approach targets ecologically relevant deciduous fractions and com-plements traditional crisp land cover classifications. We modeled fractional components using a k-NNapproach, which was based on multispectral satellite data, assisted by a digital elevation model and acontemporary map database. The modeled components were then analyzed based on landscape struc-ture indicators, and evaluated in conjunction with CORINE classification. The results indicate that bothbroadleaved forest and grassland components are widely distributed in the study area, principally orga-nized as transition zones and small patches. Landscape structure indicators show a substantial variationbased on the fractional threshold, pinpointing their dependency on the classification scheme and grain.The modeled components, on the other hand, suggest high internal variation for most CORINE classes,indicating their heterogeneous appearance and showing that the presence of deciduous components inthe landscape are not properly captured in a coarse land cover classification. To gain a realistic perceptionof the landscape, and use this information for the needs of spatial planning, both fractional results andexisting land cover classifications are needed. This is because they mutually contribute to an improvedunderstanding of habitat patterns and structures, and should be used to complement each other.
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| 6. |
- Rautio, Anne-Riikka, et al.
(författare)
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Electric double-layer capacitors based on multiwalled carbon nanotubes : can nanostructuring of the nanotubes enhance performance?
- 2015
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Ingår i: The Journal of Physical Chemistry C. - : American Chemical Society (ACS). - 1932-7447 .- 1932-7455. ; 119:7, s. 3538-3544
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Tidskriftsartikel (refereegranskat)abstract
- Supercapacitors prepared from chemically modified and vacuum filtered buckypapers were studied. The aim was to evaluate how its pore structure impacts the specific capacitance, energy, and power density in different electrolytes. The specific capacitance varies in a linear fashion with the specific surface area for nanotubes modified by the means of catalytic, low-temperature partial catalytic oxidation using cobalt oxide nanoparticles decorating the nanotubes. In contrast, electrodes composed of nanotubes preactivated in CO2 demonstrated only a minor increase in their specific capacitance, despite the observed significant increase in specific surface area. The radically improved surface area was a result of emergence and deposition of soot on the nanotubes during the activation process, as revealed by transmission electron microscopy. Among six different types of electrode materials, the CoOx decorated materials proved to have the highest specific capacitance (similar to 25 F/g in aqueous KOH and similar to 15 F/g in triethylsulfonium bis(trifluoromethylsulfonyl)imide ionic liquid). Thus, highly structured carbon nanotubes giving rise to energy and power storage densities comparable with commercial and other multiwalled carbon nanotube based electric double-layer capacitor devices were obtained.
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| 7. |
- van der Valk, Ralf J P, et al.
(författare)
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A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
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Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
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Tidskriftsartikel (refereegranskat)abstract
- Common genetic variants have been identified for adult height, but not much is known about the genetics of skeletal growth in early life. To identify common genetic variants that influence fetal skeletal growth, we meta-analyzed 22 genome-wide association studies (Stage 1; N = 28 459). We identified seven independent top single nucleotide polymorphisms (SNPs) (P < 1 × 10(-6)) for birth length, of which three were novel and four were in or near loci known to be associated with adult height (LCORL, PTCH1, GPR126 and HMGA2). The three novel SNPs were followed-up in nine replication studies (Stage 2; N = 11 995), with rs905938 in DC-STAMP domain containing 2 (DCST2) genome-wide significantly associated with birth length in a joint analysis (Stages 1 + 2; β = 0.046, SE = 0.008, P = 2.46 × 10(-8), explained variance = 0.05%). Rs905938 was also associated with infant length (N = 28 228; P = 5.54 × 10(-4)) and adult height (N = 127 513; P = 1.45 × 10(-5)). DCST2 is a DC-STAMP-like protein family member and DC-STAMP is an osteoclast cell-fusion regulator. Polygenic scores based on 180 SNPs previously associated with human adult stature explained 0.13% of variance in birth length. The same SNPs explained 2.95% of the variance of infant length. Of the 180 known adult height loci, 11 were genome-wide significantly associated with infant length (SF3B4, LCORL, SPAG17, C6orf173, PTCH1, GDF5, ZNFX1, HHIP, ACAN, HLA locus and HMGA2). This study highlights that common variation in DCST2 influences variation in early growth and adult height.
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| 8. |
- Vogelezang, Suzanne, et al.
(författare)
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Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits.
- 2020
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Ingår i: PLoS genetics. - : Public Library of Science (PLoS). - 1553-7404. ; 16:10
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Tidskriftsartikel (refereegranskat)abstract
- The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.
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