Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels
Creators: name: Taylor, Kent D.
name: Zhang, Yonghong
name: Kim, Yun Kyoung
name: Pan, Wen-Harn
name: Koh, Woon-Puay
name: Tai, E-Shyong
name: Wang, Feijie
name: Jimmy Juang, Jyh-Ming
name: Roman, Tamara S.
name: Gordon-Larsen, Penny
name: Guo, Xiuqing
name: Zhang, Rong
name: Assimes, Themistocles L.
name: Hou, Xuhong
name: Wong, Tien-Yin
name: Mohlke, Karen L.
name: Tan, Pok Chien
name: Lim, Blanche
name: Guo, Zhirong
name: Long, Jirong
name: Hwang, Mi Yeong
name: Yao, Jie
name: Fann, Cathy S.J.
name: Hixson, James
name: Rich, Stephen S.
name: Rotter, Jerome I.
name: Han, Bok-Ghee
name: Aung, Tin
name: Tan, Shu-Pei
name: Lee, Sun-Ju
name: Lin, Keng-Hung
name: Jia, Weiping
name: Sun, Liang
name: Li, Shengxu
name: Wu, Jer-Yuarn
name: Ida Chen, Yii-Der
name: Cai, Hui
name: van Dam, Rob M.
name: Tsunoda, Tatsuhiko
name: Jee, Sun-Ha
name: Sandow, Kevin
name: Peng, Hao
name: Chien, Li-Hsin
name: Gui, Lixuan
name: Adair, Linda S.
name: Feranil, Alan B.
name: Zhao, Wanting
name: Sabanayagam, Charumathi
name: Hwu, Chii-Min
name: Hsiung, Chao Agnes
name: Li, Huaixing
name: Wu, Ying
name: Sheu, Wayne H.H.
name: Salfati, Elias
name: Hu, Cheng
name: Chuang, Shu-Chun
name: Teo, Yik-Ying
name: Chen, Yuan-Tsong
name: Jung, Keum-Ji
name: Zheng, Wei
name: Shi, Jinxiu
name: Huang, Wei
name: Wang, Ya Xing
name: Dorajoo, Rajkumar
name: Tanaka, Toshihiro
name: Wang, Tzung-Dau
name: Wu, Tangchun
name: He, Jiang
name: Du, Shufa
name: Kim, Young Jin
name: Toh, Sue-Anne
name: Chen, Peng
name: Quertermous, Thomas
name: Spracklen, Cassandra N.
name: Lee, I-Te
name: Wang, Jie
name: Chang, Li-Ching
name: Johnson, Todd A.
name: Cheng, Ching-Yu
name: Yuan, Jian-Min
name: Cho, Yoon Shin
name: Liu, Jianjun
name: Isono, Masato
name: Takeuchi, Fumihiko
name: He, Meian
name: Wang, Aili
name: Xiang, Yong-Bing
name: Wei, Wen Bin
name: Sim, Xueling
name: Absher, Devin
name: Kim, Bong-Jo
name: Moon, Sanghoon
name: Gu, Dongfeng
name: Kubo, Michiaki
name: Lee, Wen-Jane
name: Jonas, Jost B.
name: Katsuya, Tomohiro
name: Nabika, Toru
name: Liang, Kae-Woei
name: Chuang, Lee-Ming
name: Fan, Qiao
name: Kato, Norihiro
name: Wang, Xu
name: Lim, Sing-Hui
name: Friedlander, Yechiel
name: Khor, Chiea-Chuen
name: Cai, Qiuyin
name: Chen, Chien-Hsiun
name: Lin, Xu
name: Shu, Xiao-Ou
name: Heng, Chew-Kiat
name: Hu, Yao
name: Cannon, Maren E.
name: Akiyama, Koichi
Publisher: name: The University of North Carolina at Chapel Hill University Libraries
Year: 2017

description: 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.