| 1. |
- Middeldorp, Christel M., et al.
(författare)
-
The Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia : design, results and future prospects
- 2019
-
Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 34:3, s. 279-300
-
Tidskriftsartikel (refereegranskat)abstract
- The impact of many unfavorable childhood traits or diseases, such as low birth weight and mental disorders, is not limited to childhood and adolescence, as they are also associated with poor outcomes in adulthood, such as cardiovascular disease. Insight into the genetic etiology of childhood and adolescent traits and disorders may therefore provide new perspectives, not only on how to improve wellbeing during childhood, but also how to prevent later adverse outcomes. To achieve the sample sizes required for genetic research, the Early Growth Genetics (EGG) and EArly Genetics and Lifecourse Epidemiology (EAGLE) consortia were established. The majority of the participating cohorts are longitudinal population-based samples, but other cohorts with data on early childhood phenotypes are also involved. Cohorts often have a broad focus and collect(ed) data on various somatic and psychiatric traits as well as environmental factors. Genetic variants have been successfully identified for multiple traits, for example, birth weight, atopic dermatitis, childhood BMI, allergic sensitization, and pubertal growth. Furthermore, the results have shown that genetic factors also partly underlie the association with adult traits. As sample sizes are still increasing, it is expected that future analyses will identify additional variants. This, in combination with the development of innovative statistical methods, will provide detailed insight on the mechanisms underlying the transition from childhood to adult disorders. Both consortia welcome new collaborations. Policies and contact details are available from the corresponding authors of this manuscript and/or the consortium websites.
|
|
| 2. |
- Tobias, Deirdre K, et al.
(författare)
-
Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
-
Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
-
Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
|
|
| 3. |
- van der Valk, Ralf J P, et al.
(författare)
-
A novel common variant in DCST2 is associated with length in early life and height in adulthood.
- 2015
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 24:4, s. 1155-68
-
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.
|
|
| 4. |
- Davies, Neil, et al.
(författare)
-
The founding charter of the Genomic Observatories Network
- 2014
-
Ingår i: GigaScience. - 2047-217X. ; 3:2
-
Tidskriftsartikel (refereegranskat)abstract
- Abstract The co-authors of this paper hereby state their intention to work together to launch the Genomic Observatories Network (GOs Network) for which this document will serve as its Founding Charter. We define a Genomic Observatory as an ecosystem and/or site subject to long-term scientific research, including (but not limited to) the sustained study of genomic biodiversity from single-celled microbes to multicellular organisms.An international group of 64 scientists first published the call for a global network of Genomic Observatories in January 2012. The vision for such a network was expanded in a subsequent paper and developed over a series of meetings in Bremen (Germany), Shenzhen (China), Moorea (French Polynesia), Oxford (UK), Pacific Grove (California, USA), Washington (DC, USA), and London (UK). While this community-building process continues, here we express our mutual intent to establish the GOs Network formally, and to describe our shared vision for its future. The views expressed here are ours alone as individual scientists, and do not necessarily represent those of the institutions with which we are affiliated.
|
|
| 5. |
- Walker, Mike, et al.
(författare)
-
Formal definition and dating of the GSSP (Global Stratotype Section and Point) for the base of the Holocene using the Greenland NGRIP ice core, and selected auxiliary records
- 2009
-
Ingår i: Journal of Quaternary Science. - : Wiley. - 1099-1417 .- 0267-8179. ; 24:1, s. 3-17
-
Forskningsöversikt (refereegranskat)abstract
- The Greenland ice core from NorthGRIP (NGRIP) contains a proxy climate record across the Pleistocene-Holocene boundary of unprecedented clarity and resolution. Analysis of an array of physical and chemical parameters within the ice enables the base of the Holocene, as reflected in the first signs of climatic warming at the end of the Younger Dryas/Greenland Stadial 1 cold phase, to be located with a high degree of precision. This climatic event is most clearly reflected in an abrupt shift in deuterium excess values, accompanied by more gradual changes in delta O-18, dust concentration, a range of chemical species, and annual layer thickness. A timescale based on multi-parameter annual layer counting provides an age of 11 700 calendar yr b2k (before AD 2000) for the base of the Holocene, with a maximum counting error of 99 yr. A proposal that an archived core from this unique sequence should constitute the Global Stratotype Section and Point (GSSP) for the base of the Holocene Series/Epoch (Quaternary System/Period) has been ratified by the International Union of Geological Sciences. Five auxiliary stratotypes for the Pleistocene-Holocene boundary have also been recognised. Copyright (C) 2008 John Wiley & Sons, Ltd.
|
|
| 6. |
- Walker, Mike, et al.
(författare)
-
The Global Stratotype Section and Point (GSSP) for the base of the Holocene Series/Epoch (Quaternary System/Period) in the NGRIP ice core
- 2008
-
Ingår i: Episodes. - 0705-3797. ; 31:2, s. 264-267
-
Tidskriftsartikel (refereegranskat)abstract
- The Greenland ice core from NorthGRIP (NGRIP) contains a proxy climate record across the Pleistocene-Holocene boundary of unprecedented clarity and resolution. Analysis of an array of physical and chemical parameters within the ice enables the base of the Holocene, as reflected in the first signs of climatic warming at the end of the Younger Dryas/Greenland Stadial 1 cold phase, to be located with a high degree of precision. This climatic event is most clearly reflected in an. abrupt shaft in deuterium excess values, accompanied by more gradual changes in delta O-18, dust concentration, a range of chemical species, and annual layer thickness. A timescale based on multi-parameter annual layer counting provides an age of 11,700 yr b2k (before AD2000) for the base of the Holocene, with, an estimated 2 sigma uncertainty of 99 yr: It is proposed that an archived core from this unique sequence should constitute the Global Stratotype Section and Point (GSSP) for the base of the Holocene Series/Epoch (Quaternary System/Period).
|
|
| 7. |
|
|
| 8. |
- de Vries, Paul S., et al.
(författare)
-
Comparison of HapMap and 1000 Genomes Reference Panels in a Large-Scale Genome-Wide Association Study
- 2017
-
Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- An increasing number of genome-wide association (GWA) studies are now using the higher resolution 1000 Genomes Project reference panel (1000G) for imputation, with the expectation that 1000G imputation will lead to the discovery of additional associated loci when compared to HapMap imputation. In order to assess the improvement of 1000G over HapMap imputation in identifying associated loci, we compared the results of GWA studies of circulating fibrinogen based on the two reference panels. Using both HapMap and 1000G imputation we performed a meta-analysis of 22 studies comprising the same 91,953 individuals. We identified six additional signals using 1000G imputation, while 29 loci were associated using both HapMap and 1000G imputation. One locus identified using HapMap imputation was not significant using 1000G imputation. The genome-wide significance threshold of 5x10(-8) is based on the number of independent statistical tests using HapMap imputation, and 1000G imputation may lead to further independent tests that should be corrected for. When using a stricter Bonferroni correction for the 1000G GWA study (P-value < 2.5x10(-8)), the number of loci significant only using HapMap imputation increased to 4 while the number of loci significant only using 1000G decreased to 5. In conclusion, 1000G imputation enabled the identification of 20% more loci than HapMap imputation, although the advantage of 1000G imputation became less clear when a stricter Bonferroni correction was used. More generally, our results provide insights that are applicable to the implementation of other dense reference panels that are under development.
|
|
| 9. |
- Kilpeläinen, Tuomas O, et al.
(författare)
-
Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
- 2016
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
-
Tidskriftsartikel (refereegranskat)abstract
- Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
|
|
| 10. |
- Leebens-Mack, James H., et al.
(författare)
-
One thousand plant transcriptomes and the phylogenomics of green plants
- 2019
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 574:7780, s. 679-
-
Tidskriftsartikel (refereegranskat)abstract
- Green plants (Viridiplantae) include around 450,000-500,000 species(1,2) of great diversity and have important roles in terrestrial and aquatic ecosystems. Here, as part of the One Thousand Plant Transcriptomes Initiative, we sequenced the vegetative transcriptomes of 1,124 species that span the diversity of plants in a broad sense (Archaeplastida), including green plants (Viridiplantae), glaucophytes (Glaucophyta) and red algae (Rhodophyta). Our analysis provides a robust phylogenomic framework for examining the evolution of green plants. Most inferred species relationships are well supported across multiple species tree and supermatrix analyses, but discordance among plastid and nuclear gene trees at a few important nodes highlights the complexity of plant genome evolution, including polyploidy, periods of rapid speciation, and extinction. Incomplete sorting of ancestral variation, polyploidization and massive expansions of gene families punctuate the evolutionary history of green plants. Notably, we find that large expansions of gene families preceded the origins of green plants, land plants and vascular plants, whereas whole-genome duplications are inferred to have occurred repeatedly throughout the evolution of flowering plants and ferns. The increasing availability of high-quality plant genome sequences and advances in functional genomics are enabling research on genome evolution across the green tree of life.
|
|
