10 Years of GWAS Discovery: Biology, Function, and Translation

Visscher, Peter M.; Wray, Naomi R.; Zhang, Qian; Sklar, Pamela; McCarthy, Mark I.; Brown, Matthew A.; Yang, Jian

doi:10.1016/j.ajhg.2017.06.005

Cited by 3,132 publications

(2,709 citation statements)

References 153 publications

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“…In an intelligible manner, some traits are governed largely by variation at individual loci, but these are likely rare among all traits of interest to evolutionary biologists. Many adaptive traits are likely driven by a large number of loci with small effect sizes, low minor allele frequency, and/or epistatic interactions (Visscher et al., 2017). GWAS of complex traits will therefore often fail to identify enough genotype–phenotype associations to explain a useful fraction of the heritability of traits of interest.…”

Section: Improving Downstream Computational Analysesmentioning

confidence: 99%

Recent advances in conservation and population genomics data analysis

Hendricks

Anderson

Antão

et al. 2018

Evolutionary Applications

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New computational methods and next‐generation sequencing (NGS) approaches have enabled the use of thousands or hundreds of thousands of genetic markers to address previously intractable questions. The methods and massive marker sets present both new data analysis challenges and opportunities to visualize, understand, and apply population and conservation genomic data in novel ways. The large scale and complexity of NGS data also increases the expertise and effort required to thoroughly and thoughtfully analyze and interpret data. To aid in this endeavor, a recent workshop entitled “Population Genomic Data Analysis,” also known as “ConGen 2017,” was held at the University of Montana. The ConGen workshop brought 15 instructors together with knowledge in a wide range of topics including NGS data filtering, genome assembly, genomic monitoring of effective population size, migration modeling, detecting adaptive genomic variation, genomewide association analysis, inbreeding depression, and landscape genomics. Here, we summarize the major themes of the workshop and the important take‐home points that were offered to students throughout. We emphasize increasing participation by women in population and conservation genomics as a vital step for the advancement of science. Some important themes that emerged during the workshop included the need for data visualization and its importance in finding problematic data, the effects of data filtering choices on downstream population genomic analyses, the increasing availability of whole‐genome sequencing, and the new challenges it presents. Our goal here is to help motivate and educate a worldwide audience to improve population genomic data analysis and interpretation, and thereby advance the contribution of genomics to molecular ecology, evolutionary biology, and especially to the conservation of biodiversity.

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Section: Improving Downstream Computational Analysesmentioning

confidence: 99%

Recent advances in conservation and population genomics data analysis

Hendricks

Anderson

Antão

et al. 2018

Evolutionary Applications

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“…Firstly, although this was a study involving thousands of individuals, by GWAS standards it was at the lower end of the range of sample sizes that have been employed for other human traits 29, 30. A decade of GWAS across multiple complex traits has shown that single effect sizes for any 1 causal variant are typically low, and thus for some traits even bigger sample sizes than ours are needed to discover them.…”

Section: Discussionmentioning

confidence: 99%

“…Both phenotype heterogeneity and sample size may have contributed to this result. Looking ahead, we note that the general lessons from GWAS applied to multiple human traits over more than a decade have brought home 3 clear messages 29, 30. The first is that all complex traits contain a genetic component, and harbor a large number of causal variants throughout the genome.…”

Section: Discussionmentioning

confidence: 99%

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study

Hernández-Fuentes

Franklin

Rebollo‐Mesa

et al. 2018

American Journal of Transplantation

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Improvements in immunosuppression have modified short‐term survival of deceased‐donor allografts, but not their rate of long‐term failure. Mismatches between donor and recipient HLA play an important role in the acute and chronic allogeneic immune response against the graft. Perfect matching at clinically relevant HLA loci does not obviate the need for immunosuppression, suggesting that additional genetic variation plays a critical role in both short‐ and long‐term graft outcomes. By combining patient data and samples from supranational cohorts across the United Kingdom and European Union, we performed the first large‐scale genome‐wide association study analyzing both donor and recipient DNA in 2094 complete renal transplant‐pairs with replication in 5866 complete pairs. We studied deceased‐donor grafts allocated on the basis of preferential HLA matching, which provided some control for HLA genetic effects. No strong donor or recipient genetic effects contributing to long‐ or short‐term allograft survival were found outside the HLA region. We discuss the implications for future research and clinical application.

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“…It is beneficial to reflect on the current state of mGWAS by drawing parallels with the history of GWAS [51][52][53]. The key idea behind GWAS is to associate genetic variants with traits of interest using large cohorts of unrelated individuals.…”

Section: Contrasting Microbiome and Traditional Genome-wide Associatimentioning

confidence: 99%

Host genetics and microbiome associations from the lens of genome wide association studies

Weissbrod

Rothschild

Barkan

et al. 2018

Preprint

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Recent studies indicate that the gut microbiome is partially heritable, motivating the need to investigate microbiome-host genome associations via microbial genome-wide association studies (mGWAS). Existing mGWAS demonstrate that microbiome-host genotypes associations are typically weak and are spread across multiple variants, similar to associations often observed in genome-wide association studies (GWAS) of complex traits. Here we reconsider mGWAS by viewing them through the lens of GWAS, and demonstrate that there are striking similarities between the challenges and pitfalls faced by the two study designs. We further advocate the mGWAS community to adopt three key lessons learned over the history of GWAS: (a) Adopting uniform data and reporting formats to facilitate replication and meta-analysis efforts; (b) enforcing stringent statistical criteria to reduce the number of false positive findings; and (c) considering the microbiome and the host genome as distinct entities, rather than studying different taxa and single nucleotide polymorphism (SNPs) separately. Finally, we anticipate that mGWAS sample sizes will have to increase by orders of magnitude to reproducibly associate the host genome with the gut microbiome.PeerJ Preprints | https://doi.org/10.7287/peerj.preprints.26615v1 | CC BY 4.0 Open Access | rec: 5

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10 Years of GWAS Discovery: Biology, Function, and Translation

Cited by 3,132 publications

References 153 publications

Recent advances in conservation and population genomics data analysis

Recent advances in conservation and population genomics data analysis

Long- and short-term outcomes in renal allografts with deceased donors: A large recipient and donor genome-wide association study

Host genetics and microbiome associations from the lens of genome wide association studies

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