Association Analyses of East Asian Individuals and Trans-Ancestry Analyses with European Individuals Reveal New Loci Associated with Cholesterol and Triglyceride Levels

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 Huey-Herng; Absher, Devin M.; 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. (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), 1770-84.

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 Huey-Herng; Absher, Devin M.; 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. (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), 1770-84.

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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 x 10-8) three novel loci associated with HDL-C near CD163-APOBEC1 (P = 7.4 x 10-9), NCOA2 (P = 1.6 x 10-8), and NID2-PTGDR (P = 4.2 x 10-8), and one novel locus associated with TG near WDR11-FGFR2 (P = 2.7 x 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 x 10-5) in subcutaneous adipose tissue for BPTF and PDGFC. Taken together, these analyses identified multiple novel lipid loci, providing new potential therapeutic targets.




JOUR



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 Huey-Herng
Absher, Devin M.
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



2017


Human Molecular Genetics

26

9

1770-84










10059

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