7
What Have We Learned from GWAS?
Benjamin F. Voight
Abstract
The last 15 years have witnessed the development and application of wellpowered 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.
B. F. Voight ()
Department of Systems Pharmacology and Translational Therapeutics and Department of
Genetics, The University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA, USA
e-mail: bvoight@upenn.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2021
K. E. Lohmueller, R. Nielsen (eds.), Human Population Genomics,
https://doi.org/10.1007/978-3-030-61646-5_7
159
What Have We Learned from GWAS?
Benjamin F. Voight
Abstract
The last 15 years have witnessed the development and application of wellpowered 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.
B. F. Voight ()
Department of Systems Pharmacology and Translational Therapeutics and Department of
Genetics, The University of Pennsylvania – Perelman School of Medicine, Philadelphia, PA, USA
e-mail: bvoight@upenn.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2021
K. E. Lohmueller, R. Nielsen (eds.), Human Population Genomics,
https://doi.org/10.1007/978-3-030-61646-5_7
159