Accurate and fast multiple-testing correction in eQTL studies.
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Abstract | In studies of expression quantitative trait loci (eQTLs), it is of increasing interest to identify eGenes, the genes whose expression levels are associated with variation at a particular genetic variant. Detecting eGenes is important for follow-up analyses and prioritization because genes are the main entities in biological processes. To detect eGenes, one typically focuses on the genetic variant with the minimum p value among all variants in cis with a gene and corrects for multiple testing to obtain a gene-level p value. For performing multiple-testing correction, a permutation test is widely used. Because of growing sample sizes of eQTL studies, however, the permutation test has become a computational bottleneck in eQTL studies. In this paper, we propose an efficient approach for correcting for multiple testing and assess eGene p values by utilizing a multivariate normal distribution. Our approach properly takes into account the linkage-disequilibrium structure among variants, and its time complexity is independent of sample size. By applying our small-sample correction techniques, our method achieves high accuracy in both small and large studies. We have shown that our method consistently produces extremely accurate p values (accuracy > 98%) for three human eQTL datasets with different sample sizes and SNP densities: the Genotype-Tissue Expression pilot dataset, the multi-region brain dataset, and the HapMap 3 dataset. |
Year of Publication | 2015
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Journal | Am J Hum Genet
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Volume | 96
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Issue | 6
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Pages | 857-68
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Date Published | 2015 Jun 04
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ISSN | 1537-6605
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URL | |
DOI | 10.1016/j.ajhg.2015.04.012
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PubMed ID | 26027500
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PubMed Central ID | PMC4457958
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Links | |
Grant list | R01 ES021801 / ES / NIEHS NIH HHS / United States
R01-GM083198 / GM / NIGMS NIH HHS / United States
R01 DA006227 / DA / NIDA NIH HHS / United States
MH090937 / MH / NIMH NIH HHS / United States
R01 MH101782 / MH / NIMH NIH HHS / United States
1R01AR063759-01A1 / AR / NIAMS NIH HHS / United States
DA006227 / DA / NIDA NIH HHS / United States
U01-DA024417 / DA / NIDA NIH HHS / United States
K25 HL080079 / HL / NHLBI NIH HHS / United States
P01 HL028481 / HL / NHLBI NIH HHS / United States
R01 MH090936 / MH / NIMH NIH HHS / United States
U01 GM092691 / GM / NIGMS NIH HHS / United States
MH090948 / MH / NIMH NIH HHS / United States
U01 DA024417 / DA / NIDA NIH HHS / United States
MH090936 / MH / NIMH NIH HHS / United States
U01 HG007598 / HG / NHGRI NIH HHS / United States
1U01HG007598-01 / HG / NHGRI NIH HHS / United States
R01-MH090553 / MH / NIMH NIH HHS / United States
R01-ES022282 / ES / NIEHS NIH HHS / United States
P01-HL28481 / HL / NHLBI NIH HHS / United States
U54 EB020403 / EB / NIBIB NIH HHS / United States
MH090941 / MH / NIMH NIH HHS / United States
5U01GM092691-04 / GM / NIGMS NIH HHS / United States
R01-ES021801 / ES / NIEHS NIH HHS / United States
HHSN261200800001E / PHS HHS / United States
R01 MH090951 / MH / NIMH NIH HHS / United States
R01-MH101782 / MH / NIMH NIH HHS / United States
K25-HL080079 / HL / NHLBI NIH HHS / United States
HHSN268201000029C / PHS HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
UH2 AR067677 / AR / NIAMS NIH HHS / United States
R01 ES022282 / ES / NIEHS NIH HHS / United States
R01 MH090948 / MH / NIMH NIH HHS / United States
R01 MH090941 / MH / NIMH NIH HHS / United States
MH090951 / MH / NIMH NIH HHS / United States
HHSN261200800001C / RC / CCR NIH HHS / United States
P01 HL030568 / HL / NHLBI NIH HHS / United States
R01 MH090937 / MH / NIMH NIH HHS / United States
UH2AR067677-01 / AR / NIAMS NIH HHS / United States
U54EB020403 / EB / NIBIB NIH HHS / United States
HHSN268201000029C / HL / NHLBI NIH HHS / United States
HHSN261200800001E / CA / NCI NIH HHS / United States
P01-HL30568 / HL / NHLBI NIH HHS / United States
R01 MH090553 / MH / NIMH NIH HHS / United States
R01 GM083198 / GM / NIGMS NIH HHS / United States
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