Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies

Local interactions between neighbouring SNPs are hypothesized to be able to capture variants missing from genome-wide association studies (GWAS) via haplotype effects but have not been thoroughly explored. We have used a new high-throughput analysis tool to probe this underexplored area through full...

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Published in:PLoS ONE
Main Authors: Wei, Wenhua, Gyenesei, Attila, Semple, Colin A M, Haley, Chris S.
Format: Article in Journal/Newspaper
Language:English
Published: 2013
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Online Access:https://research.manchester.ac.uk/en/publications/ac9ca8a9-efe7-49b4-8997-1f3c72ee144a
https://doi.org/10.1371/journal.pone.0071203
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spelling ftumanchesterpub:oai:pure.atira.dk:publications/ac9ca8a9-efe7-49b4-8997-1f3c72ee144a 2024-06-23T07:55:31+00:00 Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies Wei, Wenhua Gyenesei, Attila Semple, Colin A M Haley, Chris S. 2013-08-05 https://research.manchester.ac.uk/en/publications/ac9ca8a9-efe7-49b4-8997-1f3c72ee144a https://doi.org/10.1371/journal.pone.0071203 http://www.plosone.org/article/fetchObjectAttachment.action;jsessionid=F3EB1361BA0F190B5B527EAEED76E34C?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0071203&representation=PDF eng eng https://research.manchester.ac.uk/en/publications/ac9ca8a9-efe7-49b4-8997-1f3c72ee144a info:eu-repo/semantics/closedAccess Wei , W , Gyenesei , A , Semple , C A M & Haley , C S 2013 , ' Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies ' , PLoS ONE , vol. 8 , no. 8 , e71203 . https://doi.org/10.1371/journal.pone.0071203 article 2013 ftumanchesterpub https://doi.org/10.1371/journal.pone.0071203 2024-06-04T00:41:52Z Local interactions between neighbouring SNPs are hypothesized to be able to capture variants missing from genome-wide association studies (GWAS) via haplotype effects but have not been thoroughly explored. We have used a new high-throughput analysis tool to probe this underexplored area through full pair-wise genome scans and conventional GWAS in diastolic and systolic blood pressure and six metabolic traits in the Northern Finland Birth Cohort 1966 (NFBC1966) and the Atherosclerosis Risk in Communities study cohort (ARIC). Genome-wide significant interactions were detected in ARIC for systolic blood pressure between PLEKHA7 (a known GWAS locus for blood pressure) and GPR180 (which plays a role in vascular remodelling), and also for triglycerides as local interactions within the 11q23.3 region (replicated significantly in NFBC1966), which notably harbours several loci (BUD13, ZNF259 and APOA5) contributing to triglyceride levels. Tests of the local interactions within the 11q23.3 region conditional on the top GWAS signal suggested the presence of two independent functional variants, each with supportive evidence for their roles in gene regulation. Local interactions captured 9 additional GWAS loci identified in this study (3 significantly replicated) and 73 from previous GWAS (24 in the eight traits and 49 in related traits). We conclude that the detection of local interactions requires adequate SNP coverage of the genome and that such interactions are only likely to be detectable between SNPs in low linkage disequilibrium. Analysing local interactions is a potentially valuable complement to GWAS and can provide new insights into the biology underlying variation in complex traits. © 2013 Wei et al. Article in Journal/Newspaper Northern Finland The University of Manchester: Research Explorer PLoS ONE 8 8 e71203
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collection The University of Manchester: Research Explorer
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description Local interactions between neighbouring SNPs are hypothesized to be able to capture variants missing from genome-wide association studies (GWAS) via haplotype effects but have not been thoroughly explored. We have used a new high-throughput analysis tool to probe this underexplored area through full pair-wise genome scans and conventional GWAS in diastolic and systolic blood pressure and six metabolic traits in the Northern Finland Birth Cohort 1966 (NFBC1966) and the Atherosclerosis Risk in Communities study cohort (ARIC). Genome-wide significant interactions were detected in ARIC for systolic blood pressure between PLEKHA7 (a known GWAS locus for blood pressure) and GPR180 (which plays a role in vascular remodelling), and also for triglycerides as local interactions within the 11q23.3 region (replicated significantly in NFBC1966), which notably harbours several loci (BUD13, ZNF259 and APOA5) contributing to triglyceride levels. Tests of the local interactions within the 11q23.3 region conditional on the top GWAS signal suggested the presence of two independent functional variants, each with supportive evidence for their roles in gene regulation. Local interactions captured 9 additional GWAS loci identified in this study (3 significantly replicated) and 73 from previous GWAS (24 in the eight traits and 49 in related traits). We conclude that the detection of local interactions requires adequate SNP coverage of the genome and that such interactions are only likely to be detectable between SNPs in low linkage disequilibrium. Analysing local interactions is a potentially valuable complement to GWAS and can provide new insights into the biology underlying variation in complex traits. © 2013 Wei et al.
format Article in Journal/Newspaper
author Wei, Wenhua
Gyenesei, Attila
Semple, Colin A M
Haley, Chris S.
spellingShingle Wei, Wenhua
Gyenesei, Attila
Semple, Colin A M
Haley, Chris S.
Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies
author_facet Wei, Wenhua
Gyenesei, Attila
Semple, Colin A M
Haley, Chris S.
author_sort Wei, Wenhua
title Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies
title_short Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies
title_full Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies
title_fullStr Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies
title_full_unstemmed Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies
title_sort properties of local interactions and their potential value in complementing genome-wide association studies
publishDate 2013
url https://research.manchester.ac.uk/en/publications/ac9ca8a9-efe7-49b4-8997-1f3c72ee144a
https://doi.org/10.1371/journal.pone.0071203
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genre_facet Northern Finland
op_source Wei , W , Gyenesei , A , Semple , C A M & Haley , C S 2013 , ' Properties of Local Interactions and Their Potential Value in Complementing Genome-Wide Association Studies ' , PLoS ONE , vol. 8 , no. 8 , e71203 . https://doi.org/10.1371/journal.pone.0071203
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