TY - JOUR
T1 - Replicability and Robustness of Genome-Wide-Association Studies for Behavioral Traits
AU - Rietveld, Cornelius A.
AU - Conley, Dalton
AU - Eriksson, Nicholas
AU - Esko, Tõnu
AU - Medland, Sarah E.
AU - Vinkhuyzen, Anna A.E.
AU - Yang, Jian
AU - Boardman, Jason D.
AU - Chabris, Christopher F.
AU - Dawes, Christopher T.
AU - Domingue, Benjamin W.
AU - Hinds, David A.
AU - Johannesson, Magnus
AU - Kiefer, Amy K.
AU - Laibson, David
AU - Magnusson, Patrik K.E.
AU - Mountain, Joanna L.
AU - Oskarsson, Sven
AU - Rostapshova, Olga
AU - Teumer, Alexander
AU - Tung, Joyce Y.
AU - Visscher, Peter M.
AU - Benjamin, Daniel J.
AU - Cesarini, David
AU - Koellinger, Philipp D.
N1 - Publisher Copyright:
© The Author(s) 2014.
PY - 2014/11/20
Y1 - 2014/11/20
N2 - A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R2 ≈ 0.02%), reached genome-wide significance (p < 5 × 10−8) in a large discovery sample and were replicated in an independent sample (p <.05). The study also reported associations between educational attainment and indices of SNPs called “polygenic scores.” In three studies, we evaluated the robustness of these findings. Study 1 showed that the associations with all three SNPs were replicated in another large (N = 34,428) independent sample. We also found that the scores remained predictive (R2 ≈ 2%) in regressions with stringent controls for stratification (Study 2) and in new within-family analyses (Study 3). Our results show that large and therefore well-powered genome-wide-association studies can identify replicable genetic associations with behavioral traits. The small effect sizes of individual SNPs are likely to be a major contributing factor explaining the striking contrast between our results and the disappointing replication record of most candidate-gene studies.
AB - A recent genome-wide-association study of educational attainment identified three single-nucleotide polymorphisms (SNPs) whose associations, despite their small effect sizes (each R2 ≈ 0.02%), reached genome-wide significance (p < 5 × 10−8) in a large discovery sample and were replicated in an independent sample (p <.05). The study also reported associations between educational attainment and indices of SNPs called “polygenic scores.” In three studies, we evaluated the robustness of these findings. Study 1 showed that the associations with all three SNPs were replicated in another large (N = 34,428) independent sample. We also found that the scores remained predictive (R2 ≈ 2%) in regressions with stringent controls for stratification (Study 2) and in new within-family analyses (Study 3). Our results show that large and therefore well-powered genome-wide-association studies can identify replicable genetic associations with behavioral traits. The small effect sizes of individual SNPs are likely to be a major contributing factor explaining the striking contrast between our results and the disappointing replication record of most candidate-gene studies.
KW - behavior genetics
KW - educational attainment
KW - genome-wide association study
KW - individual differences
KW - population stratification
UR - https://www.scopus.com/pages/publications/84910659663
UR - https://www.scopus.com/pages/publications/84910659663#tab=citedBy
U2 - 10.1177/0956797614545132
DO - 10.1177/0956797614545132
M3 - Article
C2 - 25287667
AN - SCOPUS:84910659663
SN - 0956-7976
VL - 25
SP - 1975
EP - 1986
JO - Psychological Science
JF - Psychological Science
IS - 11
ER -