A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.

Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Hear...

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Main Authors: Anya Kalsbeek, Jenna Veenstra, Jason Westra, Craig Disselkoen, Kristin Koch, Katelyn A McKenzie, Jacob O'Bott, Jason Vander Woude, Karen Fischer, Greg C Shearer, William S Harris, Nathan L Tintle
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2018-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC5898718?pdf=render
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spelling doaj-fb6c36a01e904266bbb8b14d26a22f312020-11-25T00:43:15ZengPublic Library of Science (PLoS)PLoS ONE1932-62032018-01-01134e019488210.1371/journal.pone.0194882A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.Anya KalsbeekJenna VeenstraJason WestraCraig DisselkoenKristin KochKatelyn A McKenzieJacob O'BottJason Vander WoudeKaren FischerGreg C ShearerWilliam S HarrisNathan L TintleRecent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis.http://europepmc.org/articles/PMC5898718?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Anya Kalsbeek
Jenna Veenstra
Jason Westra
Craig Disselkoen
Kristin Koch
Katelyn A McKenzie
Jacob O'Bott
Jason Vander Woude
Karen Fischer
Greg C Shearer
William S Harris
Nathan L Tintle
spellingShingle Anya Kalsbeek
Jenna Veenstra
Jason Westra
Craig Disselkoen
Kristin Koch
Katelyn A McKenzie
Jacob O'Bott
Jason Vander Woude
Karen Fischer
Greg C Shearer
William S Harris
Nathan L Tintle
A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.
PLoS ONE
author_facet Anya Kalsbeek
Jenna Veenstra
Jason Westra
Craig Disselkoen
Kristin Koch
Katelyn A McKenzie
Jacob O'Bott
Jason Vander Woude
Karen Fischer
Greg C Shearer
William S Harris
Nathan L Tintle
author_sort Anya Kalsbeek
title A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.
title_short A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.
title_full A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.
title_fullStr A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.
title_full_unstemmed A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham Heart Study Offspring Cohort.
title_sort genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: framingham heart study offspring cohort.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2018-01-01
description Recent analyses have suggested a strong heritable component to circulating fatty acid (FA) levels; however, only a limited number of genes have been identified which associate with FA levels. In order to expand upon a previous genome wide association study done on participants in the Framingham Heart Study Offspring Cohort and FA levels, we used data from 2,400 of these individuals for whom red blood cell FA profiles, dietary information and genotypes are available, and then conducted a genome-wide evaluation of potential genetic variants associated with 22 FAs and 15 FA ratios, after adjusting for relevant dietary covariates. Our analysis found nine previously identified loci associated with FA levels (FADS, ELOVL2, PCOLCE2, LPCAT3, AGPAT4, NTAN1/PDXDC1, PKD2L1, HBS1L/MYB and RAB3GAP1/MCM6), while identifying four novel loci. The latter include an association between variants in CALN1 (Chromosome 7) and eicosapentaenoic acid (EPA), DHRS4L2 (Chromosome 14) and a FA ratio measuring delta-9-desaturase activity, as well as two loci associated with less well understood proteins. Thus, the inclusion of dietary covariates had a modest impact, helping to uncover four additional loci. While genome-wide association studies continue to uncover additional genes associated with circulating FA levels, much of the heritable risk is yet to be explained, suggesting the potential role of rare genetic variation, epistasis and gene-environment interactions on FA levels as well. Further studies are needed to continue to understand the complex genetic picture of FA metabolism and synthesis.
url http://europepmc.org/articles/PMC5898718?pdf=render
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