Key result
In 21,010 Japanese individuals, rs3812316 in MLXIPL was associated with a /dl decrease in triglycerides per minor C allele, and rs599839 was associated with lower LDL cholesterol.
Why the study?
Are genetic loci associated with lipid concentrations in Europeans also associated with plasma lipid profiles in a Japanese population?
Observational (n=21,010)
Are genetic loci associated with lipid concentrations in Europeans also associated with plasma lipid profiles in a Japanese population?
Genetic associations between novel loci and plasma lipid concentrations discovered in Europeans are generally conserved in the Japanese population, with some exceptions likely due to ethnic differences in linkage disequilibrium.
Answers are grounded in this paper and cite their sources.
Replicates European lipid loci in Japanese adults; extends trans-ancestry evidence but leaves clinical risk stratification open.
BACKGROUND: Recent genome wide association studies discovered seven novel loci that influence plasma concentrations of triglycerides, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in Europeans. To date, large scale replication studies using populations with known differences in genome-wide linkage disequilibrium (LD) pattern have not been undertaken. METHODS: To address this issue, we tested associations between single nucleotide polymorphisms (SNPs) within the seven novel loci and plasma lipid profiles in 21 010 Japanese individuals. RESULTS: Multiple linear regression analyses showed that the rs3812316 in MLXIPL was strongly associated with triglyceride concentrations (p approximately 3.0x10(-11), 7.1 mg/dl decrease per minor C allele) and that rs599839 in CELSR2/PSRC1/SORT1 was strongly associated with LDL cholesterol concentrations (p approximately 3.1x10(-11), 4.7 mg/dl decrease per minor G allele) in the Japanese population. SNPs near ANGPTL3, TRIB1 and GALNT2 showed evidence for associations with triglyceride concentrations (3.6x10(-6)<p<5.1x10(-5)). SNP near TRIB1 showed association with LDL cholesterol concentrations (p approximately 1.2x10(-5)). On the other hand, SNPs in NCAN/CILP2/PBX4 and MVK/MMAB were not associated with any plasma lipid profiles in the Japanese population. Ethnic differences in LD pattern would explain the lack of association between these two loci and plasma lipid concentrations in the Japanese population. CONCLUSION: Associations between the novel loci and plasma lipid concentrations were generally conserved in the Japanese population, with the exception of NCAN/CILP2/PBX4 and MVK/MMAB.
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Nakayama et al. (2009) conducted an observational in Plasma lipid profiles (n=21,010). SNPs within seven novel loci was evaluated on Triglyceride concentrations (7.1 mg/dl decrease per minor C allele, p=3.0x10(-11)). In 21,010 Japanese individuals, rs3812316 in MLXIPL was associated with a /dl decrease in triglycerides per minor C allele, and rs599839 was associated with lower LDL cholesterol.
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