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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ftdoajarticles:oai:doaj.org/article:7483eec589ba42dfac7e8fbb98b4a1c5 2023-05-15T17:42:41+02:00 Properties of local interactions and their potential value in complementing genome-wide association studies. Wenhua Wei Attila Gyenesei Colin A M Semple Chris S Haley 2013-01-01T00:00:00Z https://doi.org/10.1371/journal.pone.0071203 https://doaj.org/article/7483eec589ba42dfac7e8fbb98b4a1c5 EN eng Public Library of Science (PLoS) https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23940718/pdf/?tool=EBI https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0071203 https://doaj.org/article/7483eec589ba42dfac7e8fbb98b4a1c5 PLoS ONE, Vol 8, Iss 8, p e71203 (2013) Medicine R Science Q article 2013 ftdoajarticles https://doi.org/10.1371/journal.pone.0071203 2022-12-31T14:45:32Z 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. Article in Journal/Newspaper Northern Finland Directory of Open Access Journals: DOAJ Articles PLoS ONE 8 8 e71203 |
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English |
topic |
Medicine R Science Q |
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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. |
topic_facet |
Medicine R Science Q |
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 in Journal/Newspaper |
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://doi.org/10.1371/journal.pone.0071203 https://doaj.org/article/7483eec589ba42dfac7e8fbb98b4a1c5 |
genre |
Northern Finland |
genre_facet |
Northern Finland |
op_source |
PLoS ONE, Vol 8, Iss 8, p e71203 (2013) |
op_relation |
https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23940718/pdf/?tool=EBI https://doaj.org/toc/1932-6203 1932-6203 doi:10.1371/journal.pone.0071203 https://doaj.org/article/7483eec589ba42dfac7e8fbb98b4a1c5 |
op_doi |
https://doi.org/10.1371/journal.pone.0071203 |
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PLoS ONE |
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8 |
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8 |
container_start_page |
e71203 |
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1766144589762134016 |