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A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics

Guillaume Pare, Shihong Mao, Wei Q. Deng
doi: https://doi.org/10.1101/024067
Guillaume Pare
1Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Canada
2Population Genomics Program, Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Canada
3Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada
4Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada
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Shihong Mao
3Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, Canada
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Wei Q. Deng
5Department of Statistical Sciences, University of Toronto, Toronto, Canada
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Abstract

Despite considerable efforts, known genetic associations only explain a small fraction of predicted heritability. Regional associations combine information from multiple contiguous genetic variants and can improve variance explained at established association loci. However, regional associations are not easily amenable to estimation using summary association statistics because of sensitivity to linkage disequilibrium (LD). We now propose a novel method to estimate phenotypic variance explained by regional associations using summary statistics while accounting for LD. Our method is asymptotically equivalent to multiple regression models when no interaction or haplotype effects are present. It has multiple applications, such as ranking of genetic regions according to variance explained and derivation of regional gene scores (GS). We show that most genetic variance lies in a small proportion of the genome, and that GS derived from regional associations can improve trait prediction above optimal polygenic scores. Our results also suggest regional associations underlie known linkage peaks.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license.
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Posted August 06, 2015.
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A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics
Guillaume Pare, Shihong Mao, Wei Q. Deng
bioRxiv 024067; doi: https://doi.org/10.1101/024067
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A method to estimate the contribution of regional genetic associations to complex traits from summary association statistics
Guillaume Pare, Shihong Mao, Wei Q. Deng
bioRxiv 024067; doi: https://doi.org/10.1101/024067

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