Replicability and robustness of genome-wide-association studies for behavioral traits

LIBRIS-ID:oai:prod.swepub.kib.ki.se:130117743
http://kipublications.ki.se/Default.aspx?queryparsed=id:130117743URI
https://doi.org/10.1177/0956797614545132DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-239575URI
https://research.hhs.se/esploro/outputs/journalArticle/Replicability-and-Robustness-of-Genome-Wide-Association-Studies/991001480310106056URI

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.

Conley, DNew York University (author)
Eriksson, N23andMe (author)
Esko, TUniversity of Tartu (author)
Medland, SEQueensland Institute of Medical Research (author)
Vinkhuyzen, AAEUniversity of Queensland (AU) (author)
Yang, JUniversity of Queensland (AU),23andMe (author)
Boardman, JDUniversity of Colorado (author)
Chabris, CFUnion College (US) (author)
Dawes, CTNew York University (author)
Domingue, BWUniversity of Colorado (author)
Hinds, DA23andMe (author)
Johannesson, MagnusStockholm School of Economics,Handelshögskolan i Stockholm(Swepub:hhs)198@hhs.se (author)
Kiefer, AK23andMe (author)
Laibson, DHarvard University (US) (author)
Magnusson, PKEKarolinska Institutet,Karolinska Institutet (SE) (author)
Mountain, JL23andMe (author)
Oskarsson, SvenUppsala universitet,Statsvetenskapliga institutionen,Uppsala University (SE)(Swepub:uu)sos20331 (author)
Rostapshova, OHarvard University (US) (author)
Teumer, AGreifswald Medical School (author)
Tung, JY (author)
Visscher, PMUniversity of Queensland (AU) (author)
Benjamin, DJCornell University (US) (author)
Cesarini, DCenter for Experimental Social Science (author)
Koellinger, PDErasmus School of Economics (NL) (author)
Erasmus University (NL)New York University (creator_code:org_t)

In:Psychological science: SAGE Publications25:11, s. 1975-19861467-92800956-7976

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Medical Genetics

By the university: Karolinska Institutet; Uppsala University; Stockholm School of Economics

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