Abstract
MUFAs are unsaturated FAs with one double bond and are derived from endogenous synthesis and dietary intake. Accumulating evidence has suggested that plasma and erythrocyte MUFA levels are associated with cardiometabolic disorders, including CVD, T2D, and metabolic syndrome (MS). Previous genome-wide association studies (GWASs) have identified seven loci for plasma and erythrocyte palmitoleic and oleic acid levels in populations of European origin. To identify additional MUFA-associated loci and the potential functional variant at each locus, we performed ethnic-specific GWAS meta-analyses and trans-ethnic meta-analyses in more than 15,000 participants of Chinese and European ancestry. We identified novel genome-wide significant associations for vaccenic acid at FADS1/2 and PKD2L1 [log10(Bayes factor) ≥ 8.07] and for gondoic acid at FADS1/2 and GCKR [log10(Bayes factor) ≥ 6.22], and also observed improved fine-mapping resolutions at FADS1/2 and GCKR loci. The greatest improvement was observed at GCKR, where the number of variants in the 99% credible set was reduced from 16 (covering 94.8 kb) to 5 (covering 19.6 kb, including a missense variant rs1260326) after trans-ethnic meta-analysis. We also confirmed the previously reported associations of PKD2L1, FADS1/2, GCKR, and HIF1AN with palmitoleic acid and of FADS1/2 and LPCAT3 with oleic acid in the Chinese-specific GWAS and the trans-ethnic meta-analyses. Pathway-based analyses suggested that the identified loci were in unsaturated FA metabolism and signaling pathways. Our findings provide novel insight into the genetic basis relevant to MUFA metabolism and biology.
Highlights
MUFAs are nonessential unsaturated FAs with one double bond in the carbon chain, mainly including palmitoleic acid (16:1n-7), vaccenic acid (18:1n-7), oleic acid (18:1n9), gondoic acid (20:1n-9), erucic acid (22:1n-9), and nervonic acid (24:1n-9)
Epidemiological studies indicated that elevated levels of specific plasma and erythrocyte membrane MUFA levels were associated with increased risk of T2D [10], metabolic abnormalities [11], and CVD [12,13,14] in European populations, and studies in Chinese Hans observed that higher levels of erythrocyte palmitoleic and oleic acid levels were associated with increased risk of metabolic syndrome (MS) and T2D [15, 16]
Ethnic-specific genome-wide association study (GWAS) meta-analyses were performed for associations with palmitoleic, vaccenic, oleic, gondoic, erucic, and nervonic acids in Chinese populations, and for associations with vaccenic, gondoic, erucic, and nervonic acids in European populations (Table 1)
Summary
MUFAs are nonessential unsaturated FAs with one double bond in the carbon chain, mainly including palmitoleic acid (16:1n-7), vaccenic acid (18:1n-7), oleic acid (18:1n9), gondoic acid (20:1n-9), erucic acid (22:1n-9), and nervonic acid (24:1n-9). Epidemiological studies indicated that elevated levels of specific plasma and erythrocyte membrane MUFA levels (palmitoleic, vaccenic, erucic, and nervonic acids) were associated with increased risk of T2D [10], metabolic abnormalities [11], and CVD [12,13,14] in European populations, and studies in Chinese Hans observed that higher levels of erythrocyte palmitoleic and oleic acid levels were associated with increased risk of metabolic syndrome (MS) and T2D [15, 16] These MUFAs are of great importance to cardiometabolic diseases. We further conducted transethnic fine-mapping of the identified loci by construction of 99% credible sets
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