TY - JOUR

T1 - Replicability and Prediction

T2 - Lessons and Challenges from GWAS

AU - Marigorta, Urko M.

AU - Rodríguez, Juan Antonio

AU - Gibson, Greg

AU - Navarro, Arcadi

N1 - Publisher Copyright: © 2018 Elsevier Ltd

PY - 2018

Y1 - 2018

N2 - Since the publication of the Wellcome Trust Case Control Consortium (WTCCC) landmark study a decade ago, genome-wide association studies (GWAS) have led to the discovery of thousands of risk variants involved in disease etiology. This success story has two angles that are often overlooked. First, GWAS findings are highly replicable. This is an unprecedented phenomenon in complex trait genetics, and indeed in many areas of science, which in past decades have been plagued by false positives. At a time of increasing concerns about the lack of reproducibility, we examine the biological and methodological reasons that account for the replicability of GWAS and identify the challenges ahead. In contrast to the exemplary success of disease gene discovery, at present GWAS findings are not useful for predicting phenotypes. We close with an overview of the prospects for individualized prediction of disease risk and its foreseeable impact in clinical practice.

AB - Since the publication of the Wellcome Trust Case Control Consortium (WTCCC) landmark study a decade ago, genome-wide association studies (GWAS) have led to the discovery of thousands of risk variants involved in disease etiology. This success story has two angles that are often overlooked. First, GWAS findings are highly replicable. This is an unprecedented phenomenon in complex trait genetics, and indeed in many areas of science, which in past decades have been plagued by false positives. At a time of increasing concerns about the lack of reproducibility, we examine the biological and methodological reasons that account for the replicability of GWAS and identify the challenges ahead. In contrast to the exemplary success of disease gene discovery, at present GWAS findings are not useful for predicting phenotypes. We close with an overview of the prospects for individualized prediction of disease risk and its foreseeable impact in clinical practice.

KW - genetic architecture

KW - genetic risk score

KW - GWAS

KW - prediction

KW - replicability

U2 - 10.1016/j.tig.2018.03.005

DO - 10.1016/j.tig.2018.03.005

M3 - Journal article

C2 - 29716745

AN - SCOPUS:85046115949

VL - 34

SP - 504

EP - 517

JO - Trends in Genetics

JF - Trends in Genetics

SN - 0168-9525

IS - 7

ER -