| Literature DB >> 28334899 |
Cassandra N Spracklen1, Peng Chen2,3, Young Jin Kim4, Xu Wang5, Hui Cai6, Shengxu Li7, Jirong Long6, Ying Wu1, Ya Xing Wang8, Fumihiko Takeuchi9, Jer-Yuarn Wu10,11, Keum-Ji Jung12, Cheng Hu13, Koichi Akiyama9, Yonghong Zhang14, Sanghoon Moon4, Todd A Johnson15, Huaixing Li16, Rajkumar Dorajoo17, Meian He18, Maren E Cannon1, Tamara S Roman1, Elias Salfati19, Keng-Hung Lin20, Xiuqing Guo21, Wayne H H Sheu22,23,24,25, Devin Absher26, Linda S Adair27, Themistocles L Assimes19, Tin Aung28,29,30, Qiuyin Cai6, Li-Ching Chang10, Chien-Hsiun Chen10,11, Li-Hsin Chien31, Lee-Ming Chuang32,33,34, Shu-Chun Chuang31, Shufa Du27,35, Qiao Fan28, Cathy S J Fann10, Alan B Feranil36,37, Yechiel Friedlander38, Penny Gordon-Larsen27,35, Dongfeng Gu39, Lixuan Gui18, Zhirong Guo14, Chew-Kiat Heng40,41, James Hixson42, Xuhong Hou13, Chao Agnes Hsiung31, Yao Hu16, Mi Yeong Hwang4, Chii-Min Hwu23,43, Masato Isono9, Jyh-Ming Jimmy Juang33,44, Chiea-Chuen Khor17,45, Yun Kyoung Kim4, Woon-Puay Koh2,29, Michiaki Kubo46, I-Te Lee22,23,47, Sun-Ju Lee12, Wen-Jane Lee48,49, Kae-Woei Liang23,50,51, Blanche Lim28, Sing-Hui Lim28, Jianjun Liu2,17,52, Toru Nabika53, Wen-Harn Pan10, Hao Peng14, Thomas Quertermous19, Charumathi Sabanayagam28,29, Kevin Sandow21, Jinxiu Shi54, Liang Sun16, Pok Chien Tan28, Shu-Pei Tan28, Kent D Taylor21, Yik-Ying Teo2,5,17,55,56, Sue-Anne Toh52, Tatsuhiko Tsunoda15,57, Rob M van Dam2, Aili Wang14, Feijie Wang16, Jie Wang13, Wen Bin Wei58, Yong-Bing Xiang59, Jie Yao21, Jian-Min Yuan60,61, Rong Zhang13, Wanting Zhao28,29, Yii-Der Ida Chen21, Stephen S Rich62, Jerome I Rotter21, Tzung-Dau Wang33,44, Tangchun Wu18, Xu Lin16, Bok-Ghee Han63, Toshihiro Tanaka64,65, Yoon Shin Cho66, Tomohiro Katsuya67, Weiping Jia13, Sun-Ha Jee12, Yuan-Tsong Chen10, Norihiro Kato9, Jost B Jonas8,68, Ching-Yu Cheng28,29,30, Xiao-Ou Shu6, Jiang He7, Wei Zheng6, Tien-Yin Wong28,29,30, Wei Huang54, Bong-Jo Kim4, E-Shyong Tai2,29,52, Karen L Mohlke1, Xueling Sim2.
Abstract
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.Entities:
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Year: 2017 PMID： 28334899 PMCID： PMC6075203 DOI： 10.1093/hmg/ddx062
Source DB: PubMed Journal: Hum Mol Genet ISSN： 0964-6906 Impact factor: 6.150