Genetic loci associated with plasma phospholipid n-3 fatty acids: a meta-analysis of genome-wide association studies from the CHARGE Consortium.
Level 3 - non-randomized controlled study
Meta-analysis of observational genome-wide association studies across population cohorts
PubMed 21829377 · doi:10.1371/journal.pgen.1002193
What was done
Genome-wide association meta-analysis across five population-based cohorts comprising 8,866 subjects of European ancestry evaluating single-nucleotide polymorphisms (SNPs) associated with plasma phospholipid levels of four n-3 polyunsaturated fatty acids (PUFAs): alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA). Top representative SNPs were also evaluated in cohorts of African, Chinese, and Hispanic ancestry.
What was found
Minor alleles in FADS1 and FADS2 were associated with higher ALA (p = 3 x 10^-64) and lower EPA (p = 5 x 10^-58) and DPA (p = 4 x 10^-154). Minor alleles in ELOVL2 were associated with higher EPA (p = 2 x 10^-12) and DPA (p = 1 x 10^-43) and lower DHA (p = 1 x 10^-15). DPA was also associated with SNPs in GCKR (p = 1 x 10^-8). A representative FADS2 SNP (rs1535) weakened the association between ALA and EPA. Associations were similar across African, Chinese, and Hispanic ancestries for FADS1, but less consistent for ELOVL2.
Why it matters
This study demonstrates that common genetic variation in key desaturase (FADS1/2) and elongase (ELOVL2) pathway genes, as well as GCKR, strongly influences endogenous biosynthesis and circulating levels of cardioprotective n-3 fatty acids.
Limits
The abstract reports p-values but no effect sizes, variance explained, or confidence intervals. The primary GWAS was restricted to European-ancestry cohorts; sample sizes and detailed findings for non-European cohorts are not specified. Dietary intake of PUFAs was not described in the abstract.
Cited by
- supports Genetic polymorphisms affect the efficiency with which individuals convert ALA into EPA and DHA.