Fast set-based association analysis using summary data from GWAS identifies novel gene loci for human complex traits.
We propose a method (fastBAT) that performs a fast set-based association analysis for human complex traits using summary-level data from genome-wide association studies (GWAS) and linkage disequilibrium (LD) data from a reference sample with individual-level genotypes. We demonstrate using simulations and analyses of real datasets that fastBAT is more accurate and orders of magnitude faster than the prevailing methods. Using fastBAT, we analyze summary data from the latest meta-analyses of GWAS on 150,064-339,224 individuals for height, body mass index (BMI), and schizophrenia. We identify 6 novel gene loci for height, 2 for BMI, and 3 for schizophrenia at PfastBAT < 5 × 10(-8). The gain of power is due to multiple small independent association signals at these loci (e.g. the THRB and FOXP1 loci for schizophrenia). The method is general and can be applied to GWAS data for all complex traits and diseases in humans and to such data in other species.
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.|Centre for Systems Genomics, School of BioSciences, The University of Melbourne, Parkville 3010, Victoria, Australia.
Andrew
A
Bakshi
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.|Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Zhihong
Z
Zhu
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.|Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Anna A E
AA
Vinkhuyzen
Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, 7 George Square, Edinburgh, UK.|Department of Psychology, University of Edinburgh, Edinburgh, UK.
W David
WD
Hill
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.|Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.
Allan F
AF
McRae
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.|Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.|The University of Queensland Diamantina Institute, The Translation Research Institute, Brisbane, Queensland, Australia.
Peter M
PM
Visscher
Queensland Brain Institute, The University of Queensland, Brisbane, Queensland 4072, Australia.|Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland 4072, Australia.|The University of Queensland Diamantina Institute, The Translation Research Institute, Brisbane, Queensland, Australia.
Jian
J
Yang
D001827:Body Height; D015992:Body Mass Index; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D016208:Databases, Factual; D005260:Female; D055106:Genome-Wide Association Study / Q000379:methods*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019655:Quantitative Trait, Heritable; D012559:Schizophrenia / Q000235:genetics