A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates

Framingham heart study offspring cohort

Anya Kalsbeek, Jenna Veenstra, Jason Westra, Craig Disselkoen, Kristin Koch, Katelyn A. McKenzie, Jacob O’Bott, Jason Vander Woude, Karen Fischer, Gregory C. Shearer, William S. Harris, Nathan L. Tintle

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere0194882
JournalPloS one
Volume13
Issue number4
DOIs
StatePublished - Apr 1 2018

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Genome-Wide Association Study
cohort studies
Blood
Cohort Studies
erythrocytes
Fatty Acids
Genes
Erythrocytes
heart
Cells
fatty acids
loci
fatty acid composition
chromosomes
Association reactions
Chromosomes
fatty acid metabolism
genotype-environment interaction
epistasis
eicosapentaenoic acid

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Kalsbeek, A., Veenstra, J., Westra, J., Disselkoen, C., Koch, K., McKenzie, K. A., ... Tintle, N. L. (2018). A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham heart study offspring cohort. PloS one, 13(4), [e0194882]. https://doi.org/10.1371/journal.pone.0194882
Kalsbeek, Anya ; Veenstra, Jenna ; Westra, Jason ; Disselkoen, Craig ; Koch, Kristin ; McKenzie, Katelyn A. ; O’Bott, Jacob ; Woude, Jason Vander ; Fischer, Karen ; Shearer, Gregory C. ; Harris, William S. ; Tintle, Nathan L. / A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates : Framingham heart study offspring cohort. In: PloS one. 2018 ; Vol. 13, No. 4.
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abstract = "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.",
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Kalsbeek, A, Veenstra, J, Westra, J, Disselkoen, C, Koch, K, McKenzie, KA, O’Bott, J, Woude, JV, Fischer, K, Shearer, GC, Harris, WS & Tintle, NL 2018, 'A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates: Framingham heart study offspring cohort', PloS one, vol. 13, no. 4, e0194882. https://doi.org/10.1371/journal.pone.0194882

A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates : Framingham heart study offspring cohort. / Kalsbeek, Anya; Veenstra, Jenna; Westra, Jason; Disselkoen, Craig; Koch, Kristin; McKenzie, Katelyn A.; O’Bott, Jacob; Woude, Jason Vander; Fischer, Karen; Shearer, Gregory C.; Harris, William S.; Tintle, Nathan L.

In: PloS one, Vol. 13, No. 4, e0194882, 01.04.2018.

Research output: Contribution to journalArticle

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T1 - A genome-wide association study of red-blood cell fatty acids and ratios incorporating dietary covariates

T2 - Framingham heart study offspring cohort

AU - Kalsbeek, Anya

AU - Veenstra, Jenna

AU - Westra, Jason

AU - Disselkoen, Craig

AU - Koch, Kristin

AU - McKenzie, Katelyn A.

AU - O’Bott, Jacob

AU - Woude, Jason Vander

AU - Fischer, Karen

AU - Shearer, Gregory C.

AU - Harris, William S.

AU - Tintle, Nathan L.

PY - 2018/4/1

Y1 - 2018/4/1

N2 - 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.

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