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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 simulatio...

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Detalles Bibliográficos
Autores principales: Bakshi, Andrew, Zhu, Zhihong, Vinkhuyzen, Anna A. E., Hill, W. David, McRae, Allan F., Visscher, Peter M., Yang, Jian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5015118/
https://www.ncbi.nlm.nih.gov/pubmed/27604177
http://dx.doi.org/10.1038/srep32894
Descripción
Sumario: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 P(fastBAT) < 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.