Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels.

Published

Journal Article

Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P < 5 × 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 × 10-9), NCOA2 (P = 1.6 × 10-8), and NID2-PTGDR (P = 4.2 × 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 × 10-10). Conditional analyses identified a second signal near CD163-APOBEC1. We then combined results from the East Asian meta-analysis with association results from up to 187,365 European individuals from the Global Lipids Genetics Consortium in a trans-ancestry meta-analysis. This analysis identified (log10Bayes Factor ≥6.1) eight additional novel lipid loci. Among the twelve total loci identified, the index variants at eight loci have demonstrated at least nominal significance with other metabolic traits in prior studies, and two loci exhibited coincident eQTLs (P < 1 × 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.

Full Text

Duke Authors

Cited Authors

  • Spracklen, CN; Chen, P; Kim, YJ; Wang, X; Cai, H; Li, S; Long, J; Wu, Y; Wang, YX; Takeuchi, F; Wu, J-Y; Jung, K-J; Hu, C; Akiyama, K; Zhang, Y; Moon, S; Johnson, TA; Li, H; Dorajoo, R; He, M; Cannon, ME; Roman, TS; Salfati, E; Lin, K-H; Guo, X; Sheu, WHH; Absher, D; Adair, LS; Assimes, TL; Aung, T; Cai, Q; Chang, L-C; Chen, C-H; Chien, L-H; Chuang, L-M; Chuang, S-C; Du, S; Fan, Q; Fann, CSJ; Feranil, AB; Friedlander, Y; Gordon-Larsen, P; Gu, D; Gui, L; Guo, Z; Heng, C-K; Hixson, J; Hou, X; Hsiung, CA; Hu, Y; Hwang, MY; Hwu, C-M; Isono, M; Juang, J-MJ; Khor, C-C; Kim, YK; Koh, W-P; Kubo, M; Lee, I-T; Lee, S-J; Lee, W-J; Liang, K-W; Lim, B; Lim, S-H; Liu, J; Nabika, T; Pan, W-H; Peng, H; Quertermous, T; Sabanayagam, C; Sandow, K; Shi, J; Sun, L; Tan, PC; Tan, S-P; Taylor, KD; Teo, Y-Y; Toh, S-A; Tsunoda, T; van Dam, RM; Wang, A; Wang, F; Wang, J; Wei, WB; Xiang, Y-B; Yao, J; Yuan, J-M; Zhang, R; Zhao, W; Chen, Y-DI; Rich, SS; Rotter, JI; Wang, T-D; Wu, T; Lin, X; Han, B-G; Tanaka, T; Cho, YS; Katsuya, T; Jia, W; Jee, S-H; Chen, Y-T; Kato, N; Jonas, JB; Cheng, C-Y; Shu, X-O; He, J; Zheng, W; Wong, T-Y; Huang, W; Kim, B-J; Tai, E-S; Mohlke, KL; Sim, X

Published Date

  • May 2017

Published In

Volume / Issue

  • 26 / 9

Start / End Page

  • 1770 - 1784

PubMed ID

  • 28334899

Pubmed Central ID

  • 28334899

Electronic International Standard Serial Number (EISSN)

  • 1460-2083

International Standard Serial Number (ISSN)

  • 0964-6906

Digital Object Identifier (DOI)

  • 10.1093/hmg/ddx062

Language

  • eng