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

Authors
 Cassandra N. Spracklen  ;  Peng Chen  ;  Young Jin Kim  ;  Xu Wang  ;  Hui Cai  ;  Shengxu Li  ;  Jirong Long  ;  Ying Wu  ;  Ya Xing Wang  ;  Fumihiko Takeuchi  ;  Jer-Yuarn Wu  ;  Keum-Ji Jung  ;  Cheng Hu  ;  Koichi Akiyama  ;  Yonghong Zhang  ;  Sanghoon Moon  ;  Todd A Johnson  ;  Huaixing Li  ;  Rajkumar Dorajoo  ;  Meian He  ;  Maren E Cannon  ;  Tamara S Roman  ;  Elias Salfati  ;  Keng-Hung Lin  ;  Xiuqing Guo  ;  Wayne H H Sheu  ;  Devin Absher  ;  Linda S Adair  ;  Themistocles L Assimes  ;  Tin Aung  ;  Qiuyin Cai  ;  Li-Ching Chang  ;  Chien-Hsiun Chen  ;  Li-Hsin Chien  ;  Lee-Ming Chuang  ;  Shu-Chun Chuang  ;  Shufa Du  ;  Qiao Fan  ;  Cathy S J Fann  ;  Alan B Feranil  ;  Yechiel Friedlander  ;  Penny Gordon-Larsen  ;  Dongfeng Gu  ;  Lixuan Gui  ;  Zhirong Guo  ;  Chew-Kiat Heng  ;  James Hixson  ;  Xuhong Hou  ;  Chao Agnes Hsiung  ;  Yao Hu  ;  Mi Yeong Hwang  ;  Chii-Min Hwu  ;  Masato Isono  ;  Jyh-Ming Jimmy Juang  ;  Chiea-Chuen Khor  ;  Yun Kyoung Kim  ;  Woon-Puay Koh  ;  Michiaki Kubo  ;  I-Te Lee  ;  Sun-Ju Lee  ;  Wen-Jane Lee  ;  Kae-Woei Liang  ;  Blanche Lim  ;  Sing-Hui Lim  ;  Jianjun Liu  ;  Toru Nabika  ;  Wen-Harn Pan  ;  Hao Peng  ;  Thomas Quertermous  ;  Charumathi Sabanayagam  ;  Kevin Sandow  ;  Jinxiu Shi  ;  Liang Sun  ;  Pok Chien Tan  ;  Shu-Pei Tan  ;  Kent D Taylor  ;  Yik-Ying Teo  ;  Sue-Anne Toh  ;  Tatsuhiko Tsunoda  ;  Rob M van Dam  ;  Aili Wang  ;  Feijie Wang  ;  Jie Wang  ;  Wen Bin Wei  ;  Yong-Bing Xiang  ;  Jie Yao  ;  Jian-Min Yuan  ;  Rong Zhang  ;  Wanting Zhao  ;  Yii-Der Ida Chen  ;  Stephen S Rich  ;  Jerome I Rotter  ;  Tzung-Dau Wang  ;  Tangchun Wu  ;  Xu Lin  ;  Bok-Ghee Han  ;  Toshihiro Tanaka  ;  Yoon Shin Cho  ;  Tomohiro Katsuya  ;  Weiping Jia  ;  Sun-Ha Jee  ;  Yuan-Tsong Chen  ;  Norihiro Kato  ;  Jost B Jonas  ;  Ching-Yu Cheng  ;  Xiao-Ou Shu  ;  Jiang He  ;  Wei Zheng  ;  Tien-Yin Wong  ;  Wei Huang  ;  Bong-Jo Kim  ;  E-Shyong Tai  ;  Karen L Mohlke  ;  Xueling Sim 
Citation
 HUMAN MOLECULAR GENETICS, Vol.26(9) : 1770-1784, 2017 
Journal Title
 HUMAN MOLECULAR GENETICS 
ISSN
 0964-6906 
Issue Date
2017
MeSH
Adult ; Alleles ; Asian Continental Ancestry Group/genetics ; Cholesterol/genetics* ; Cholesterol/metabolism ; Ethnic Groups ; European Continental Ancestry Group/genetics ; Female ; Gene Frequency/genetics ; Genetic Association Studies/methods ; Genome-Wide Association Study ; Humans ; Linkage Disequilibrium/genetics ; Lipids/genetics ; Lipoproteins, HDL/genetics ; Lipoproteins, LDL/genetics ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci ; Triglycerides/genetics* ; Triglycerides/metabolism
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.
Full Text
https://academic.oup.com/hmg/article/26/9/1770/3039197
DOI
10.1093/hmg/ddx062
Appears in Collections:
4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jung, Keum Ji(정금지) ORCID logo https://orcid.org/0000-0003-4993-0666
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/160609
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