Genome-wide association study of plasma polyunsaturated fatty acids in the InCHIANTI Study.
Level 4 - case-series / case-control
Cross-sectional genome-wide association study with an independent replication cohort.
PubMed 19148276 · doi:10.1371/journal.pgen.1000338
What was done
A genome-wide association study of plasma concentrations of six omega-3 and omega-6 polyunsaturated fatty acids was performed in 1,075 participants from the InCHIANTI cohort. Significant associations were tested for replication in an independent sample of 1,076 participants from the GOLDN study.
What was found
The strongest association with plasma PUFAs mapped to the FADS1, FADS2, and FADS3 gene cluster on chromosome 11. Specifically, rs174537 near FADS1 was associated with arachidonic acid (AA; p = 5.95 x 10^-46), accounting for 18.6% of the additive variance in AA concentrations, with minor allele homozygotes having lower AA. The same SNP associated with eicosadienoic acid (EDA; p = 6.78 x 10^-9) and eicosapentaenoic acid (EPA; p = 1.07 x 10^-14), associations confirmed in the GOLDN cohort. Alleles associated with higher AA, EDA, and EPA also correlated with higher LDL cholesterol and total cholesterol. On chromosome 6, an ELOVL2 SNP (rs953413) associated with EPA in InCHIANTI (p = 1.1 x 10^-6) and with docosapentaenoic acid and DHA, but not EPA, in GOLDN.
Why it matters
This study demonstrates that common genetic polymorphisms in desaturase and elongase genes explain a substantial proportion of inter-individual variation in circulating polyunsaturated fatty acids and lipid profiles.
Limits
The abstract does not describe dietary fatty acid intake or adjust for gene-diet interactions. The specific fatty acid associations for the ELOVL2 locus differed between the discovery and replication cohorts, and the analysis is cross-sectional.
Cited by
- supports Mutations in the fatty acid desaturase (FADS) genes substantially affect omega-6 arachidonic acid levels but explain only 2 to 3% of the variability in omega-3 levels.