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What HaveWe Learned fromGWAS?

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Abstract

The last 15 years have witnessed the development and application of well-powered genome-wide association studies (GWAS), an approach in which a large number of genetic markers across the entire genome are tested for association with complex phenotypes in large, unrelated cohorts. This approach has led to hundreds of bona fide and reproducible associations between genotype and phenotype in human populations, with additional studies poised to dramatically increase this number in the near term. In the midst of this discovery process, a retrospective pause is warranted to consider how the field has evolved and what practically has been learned over this short time period. The success of GWAS as an approach to uncover the biological basis for disease required a number of key innovations and developments, both methodologically and technologically. Once those hurdles had been overcome, a number of basic insights have been revealed about complex traits directly from GWAS, most notably regarding the polygenic architecture of complex disease, shared genetic susceptibility across ethnicities, and success discovering previously unknown biology underlying disease progression. The following chapter describes these and other insights learned along the way, with examples from trait analyses and empirical observation. I conclude with considerations for future expected experiments as GWAS leaves the phase of locus discovery to systematic epiphany over the biological underpinnings of complex traits in humans.

Keywords

  • Genome-wide association study
  • Complex traits
  • Heritability
  • Genetic architecture
  • Population stratification
  • Systems biology

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Fig. 7.1

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Acknowledgements

The author is indebted to Mark J. Daly for the motivating idea and most of the data contributing to Fig. 7.1.

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Correspondence to Benjamin F. Voight .

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Voight, B.F. (2021). What HaveWe Learned fromGWAS?. In: Lohmueller, K.E., Nielsen, R. (eds) Human Population Genomics. Springer, Cham. https://doi.org/10.1007/978-3-030-61646-5_7

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