Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression

Lindsay M. Reynolds, Timothy D. Howard, Ingo Ruczinski, Kanika Kanchan, Michael C. Seeds, Rasika Mathias, Floyd H. Chilton

Research output: Contribution to journalArticle

Abstract

Omega-6 (n-6) and omega-3 (n-3) long ( 20 carbon) chain polyunsaturated fatty acids (LC-PUFAs) play a critical role in human health and disease. Biosynthesis of LC-PUFAs from dietary 18 carbon PUFAs in tissues such as the liver is highly associated with genetic variation within the fatty acid desaturase (FADS) gene cluster, containing FADS1 and FADS2 that encode the rate-limiting desaturation enzymes in the LC-PUFA biosynthesis pathway. However, the molecular mechanisms by which FADS genetic variants affect LC-PUFA biosynthesis, and in which tissues, are unclear. The current study examined associations between common single nucleotide polymorphisms (SNPs) within the FADS gene cluster and FADS1 and FADS2 gene expression in 44 different human tissues (sample sizes ranging 70–361) from the Genotype-Tissue Expression (GTEx) Project. FADS1 and FADS2 expression were detected in all 44 tissues. Significant cis-eQTLs (within 1 megabase of each gene, False Discovery Rate, FDR0.05, as defined by GTEx) were identified in 12 tissues for FADS1 gene expression and 23 tissues for FADS2 gene expression. Six tissues had significant (FDR 0.05) eQTLs associated with both FADS1 and FADS2 (including artery, esophagus, heart, muscle, nerve, and thyroid). Interestingly, the identified eQTLs were consistently found to be associated in opposite directions for FADS1 and FADS2 expression. Taken together, findings from this study suggest common SNPs within the FADS gene cluster impact the transcription of FADS1 and FADS2 in numerous tissues and raise important questions about how the inverse expression of these two genes impact intermediate molecular (such a LC-PUFA and LC-PUFA-containing glycero-lipid levels) and ultimately clinical phenotypes associated with inflammatory diseases and brain health.

Original languageEnglish (US)
Article numbere0194610
JournalPLoS One
Volume13
Issue number3
DOIs
StatePublished - Mar 1 2018

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Fatty Acid Desaturases
stearoyl-CoA desaturase
Gene expression
Tissue
Gene Expression
gene expression
Carbon
polyunsaturated fatty acids
Unsaturated Fatty Acids
carbon
Genes
Biosynthesis
Multigene Family
multigene family
biosynthesis
Polymorphism
single nucleotide polymorphism
Single Nucleotide Polymorphism
Nucleotides
Genotype

ASJC Scopus subject areas

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

Cite this

Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression. / Reynolds, Lindsay M.; Howard, Timothy D.; Ruczinski, Ingo; Kanchan, Kanika; Seeds, Michael C.; Mathias, Rasika; Chilton, Floyd H.

In: PLoS One, Vol. 13, No. 3, e0194610, 01.03.2018.

Research output: Contribution to journalArticle

Reynolds, Lindsay M. ; Howard, Timothy D. ; Ruczinski, Ingo ; Kanchan, Kanika ; Seeds, Michael C. ; Mathias, Rasika ; Chilton, Floyd H. / Tissue-specific impact of FADS cluster variants on FADS1 and FADS2 gene expression. In: PLoS One. 2018 ; Vol. 13, No. 3.
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