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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Autores principales:	Wenhua Wei, Attila Gyenesei, Colin A M Semple, Chris S Haley
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7483eec589ba42dfac7e8fbb98b4a1c5
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spelling	oai:doaj.org-article:7483eec589ba42dfac7e8fbb98b4a1c52021-11-18T09:01:10ZProperties of local interactions and their potential value in complementing genome-wide association studies.1932-620310.1371/journal.pone.0071203https://doaj.org/article/7483eec589ba42dfac7e8fbb98b4a1c52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23940718/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Local 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.Wenhua WeiAttila GyeneseiColin A M SempleChris S HaleyPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e71203 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Wenhua Wei Attila Gyenesei Colin A M Semple Chris S Haley Properties of local interactions and their potential value in complementing genome-wide association studies.
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.
format	article
author	Wenhua Wei Attila Gyenesei Colin A M Semple Chris S Haley
author_facet	Wenhua Wei Attila Gyenesei Colin A M Semple Chris S Haley
author_sort	Wenhua Wei
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.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/7483eec589ba42dfac7e8fbb98b4a1c5
work_keys_str_mv	AT wenhuawei propertiesoflocalinteractionsandtheirpotentialvalueincomplementinggenomewideassociationstudies AT attilagyenesei propertiesoflocalinteractionsandtheirpotentialvalueincomplementinggenomewideassociationstudies AT colinamsemple propertiesoflocalinteractionsandtheirpotentialvalueincomplementinggenomewideassociationstudies AT chrisshaley propertiesoflocalinteractionsandtheirpotentialvalueincomplementinggenomewideassociationstudies
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Properties of local interactions and their potential value in complementing genome-wide association studies.

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