Human molecular genetics · 2017

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

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

Аннотация

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.

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

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