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

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 HeMaren 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

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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 metaanalyses 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=7.4×10-10), 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.

Original languageEnglish
Pages (from-to)1770-1784
Number of pages15
JournalHuman molecular genetics
Volume26
Issue number9
DOIs
Publication statusPublished - 01-05-2017

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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    Spracklen, C. N., Chen, P., Kim, Y. J., Wang, X., Cai, H., Li, S., Long, J., Wu, Y., Wang, Y. X., Takeuchi, F., Wu, J. Y., Jung, K. J., Hu, C., Akiyama, K., Zhang, Y., Moon, S., Johnson, T. A., Li, H., Dorajoo, R., ... Sim, X. (2017). Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels. Human molecular genetics, 26(9), 1770-1784. https://doi.org/10.1093/hmg/ddx062