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Epidemiological studies suggest that levels of n-3 and n-6 long-chain polyunsaturated fatty acids are associated with risk of cardio-metabolic outcomes across different ethnic groups. Recent genome-wide association studies in populations of European ancestry have identified several loci associated with plasma and/or erythrocyte polyunsaturated fatty acids. To identify additional novel loci, we carried out a genome-wide association study in two population-based cohorts consisting of 3521 Chinese participants, followed by a trans-ethnic meta-analysis with meta-analysis results from 8962 participants of European ancestry. Four novel loci ( MYB, AGPAT4, DGAT2  and  PPT2 ) reached genome-wide significance in the trans-ethnic meta-analysis (log10(Bayes Factor) ≥ 6). Of them, associations of  MYB  and  AGPAT4  with docosatetraenoic acid (log10(Bayes Factor) = 11.5 and 8.69, respectively) also reached genome-wide significance in the Chinese-specific genome-wide association analyses ( P  = 4.15 × 10 −14  and 4.30 × 10 −12 , respectively), while associations of  DGAT2  with gamma-linolenic acid (log10(Bayes Factor) = 6.16) and of  PPT2  with docosapentaenoic acid (log10(Bayes Factor) = 6.24) were nominally significant in both Chinese- and European-specific genome-wide association analyses ( P  ≤ 0.003). We also confirmed previously reported loci including  FADS1 ,  NTAN1 ,  NRBF2 ,  ELOVL2  and  GCKR . Different effect sizes in  FADS1  and independent association signals in  ELOVL2  were observed. These results provide novel insight into the genetic background of polyunsaturated fatty acids and their differences between Chinese and European populations.

human molecular genetics

Genome-wide meta-analyses identify novel loci associated with n-3 and n-6 polyunsaturated fatty acid levels in Chinese and European-ancestry populations