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

Hum Mol Genet 2017 05;26(9):1770-1784

Saw Swee Hock School of Public Health, National University Health System, National University of Singapore, Singapore, Singapore.

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.

Download full-text PDF

Source
http://dx.doi.org/10.1093/hmg/ddx062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6075203PMC
May 2017
103 Reads

Publication Analysis

Top Keywords

east asian
8
asian individuals
8
loci associated
8
lipoprotein cholesterol
8
cholesterol
5
allele frequencies
4
structure allele
4
disequilibrium structure
4
frequencies ancestry
4
ancestry groups
4
groups studies
4
linkage disequilibrium
4
studies additional
4
ldl-c triglycerides
4
high-density lipoprotein
4
cholesterol high-density
4
total cholesterol
4
including total
4
cholesterol hdl-c
4
hdl-c low-density
4

Similar Publications