Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference

Wanqing Wen; Norihiro Kato; Joo Yeon Hwang; Xingyi Guo; Yasuharu Tabara; Huaixing Li; Rajkumar Dorajoo; Xiaobo Yang; Fuu Jen Tsai; Shengxu Li; Ying Wu; Tangchun Wu; Soriul Kim; Xiuqing Guo; Jun Liang; Dmitry Shungin; Linda S. Adair; Koichi Akiyama; Matthew Allison; Qiuyin Cai; Li Ching Chang; Chien Hsiun Chen; Yuan Tsong Chen; Yoon Shin Cho; Bo Youl Choi; Yutang Gao; Min Jin Go; Dongfeng Gu; Bok Ghee Han; Meian He; James E. Hixson; Yanling Hu; Tao Huang; Masato Isono; Keum Ji Jung; Daehee Kang; Young Jin Kim; Yoshikuni Kita; Juyoung Lee; Nanette R. Lee; Jeannette Lee; Yiqin Wang; Jian Jun Liu; Jirong Long; Sanghoon Moon; Yasuyuki Nakamura; Masahiro Nakatochi; Keizo Ohnaka; Dabeeru Rao; Jiajun Shi; Jae Woong Sull; Aihua Tan; Hirotsugu Ueshima; Chen Wu; Yong Bing Xiang; Ken Yamamoto; Jie Yao; Xingwang Ye; Mitsuhiro Yokota; Xiaomin Zhang; Yan Zheng; Lu Qi; Jerome I. Rotter; Sun Ha Jee; Dongxin Lin; Karen L. Mohlke; Jiang He; Zengnan Mo; Jer Yuarn Wu; E. Shyong Tai; Xu Lin; Tetsuro Miki; Bong Jo Kim; Fumihiko Takeuchi; Wei Zheng; Xiao Ou Shu

doi:10.1038/srep17958

Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference

Wanqing Wen, Norihiro Kato, Joo Yeon Hwang, Xingyi Guo, Yasuharu Tabara, Huaixing Li, Rajkumar Dorajoo, Xiaobo Yang, Fuu Jen Tsai, Shengxu Li, Ying Wu, Tangchun Wu, Soriul Kim, Xiuqing Guo, Jun Liang, Dmitry Shungin, Linda S. Adair, Koichi Akiyama, Matthew Allison, Qiuyin CaiLi Ching Chang, Chien Hsiun Chen, Yuan Tsong Chen, Yoon Shin Cho, Bo Youl Choi, Yutang Gao, Min Jin Go, Dongfeng Gu, Bok Ghee Han, Meian He, James E. Hixson, Yanling Hu, Tao Huang, Masato Isono, Keum Ji Jung, Daehee Kang, Young Jin Kim, Yoshikuni Kita, Juyoung Lee, Nanette R. Lee, Jeannette Lee, Yiqin Wang, Jian Jun Liu, Jirong Long, Sanghoon Moon, Yasuyuki Nakamura, Masahiro Nakatochi, Keizo Ohnaka, Dabeeru Rao, Jiajun Shi, Jae Woong Sull, Aihua Tan, Hirotsugu Ueshima, Chen Wu, Yong Bing Xiang, Ken Yamamoto, Jie Yao, Xingwang Ye, Mitsuhiro Yokota, Xiaomin Zhang, Yan Zheng, Lu Qi, Jerome I. Rotter, Sun Ha Jee, Dongxin Lin, Karen L. Mohlke, Jiang He, Zengnan Mo, Jer Yuarn Wu, E. Shyong Tai, Xu Lin, Tetsuro Miki, Bong Jo Kim, Fumihiko Takeuchi, Wei Zheng, Xiao Ou Shu

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Abstract

Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.

Original language	English
Article number	17958
Journal	Scientific reports
Volume	6
DOIs	https://doi.org/10.1038/srep17958
State	Published - Jan 20 2016

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Wen, W., Kato, N., Hwang, J. Y., Guo, X., Tabara, Y., Li, H., Dorajoo, R., Yang, X., Tsai, F. J., Li, S., Wu, Y., Wu, T., Kim, S., Guo, X., Liang, J., Shungin, D., Adair, L. S., Akiyama, K., Allison, M., ... Shu, X. O. (2016). Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference. Scientific reports, 6, [17958]. https://doi.org/10.1038/srep17958

Wen, Wanqing ; Kato, Norihiro ; Hwang, Joo Yeon ; Guo, Xingyi ; Tabara, Yasuharu ; Li, Huaixing ; Dorajoo, Rajkumar ; Yang, Xiaobo ; Tsai, Fuu Jen ; Li, Shengxu ; Wu, Ying ; Wu, Tangchun ; Kim, Soriul ; Guo, Xiuqing ; Liang, Jun ; Shungin, Dmitry ; Adair, Linda S. ; Akiyama, Koichi ; Allison, Matthew ; Cai, Qiuyin ; Chang, Li Ching ; Chen, Chien Hsiun ; Chen, Yuan Tsong ; Cho, Yoon Shin ; Choi, Bo Youl ; Gao, Yutang ; Go, Min Jin ; Gu, Dongfeng ; Han, Bok Ghee ; He, Meian ; Hixson, James E. ; Hu, Yanling ; Huang, Tao ; Isono, Masato ; Jung, Keum Ji ; Kang, Daehee ; Kim, Young Jin ; Kita, Yoshikuni ; Lee, Juyoung ; Lee, Nanette R. ; Lee, Jeannette ; Wang, Yiqin ; Liu, Jian Jun ; Long, Jirong ; Moon, Sanghoon ; Nakamura, Yasuyuki ; Nakatochi, Masahiro ; Ohnaka, Keizo ; Rao, Dabeeru ; Shi, Jiajun ; Sull, Jae Woong ; Tan, Aihua ; Ueshima, Hirotsugu ; Wu, Chen ; Xiang, Yong Bing ; Yamamoto, Ken ; Yao, Jie ; Ye, Xingwang ; Yokota, Mitsuhiro ; Zhang, Xiaomin ; Zheng, Yan ; Qi, Lu ; Rotter, Jerome I. ; Jee, Sun Ha ; Lin, Dongxin ; Mohlke, Karen L. ; He, Jiang ; Mo, Zengnan ; Wu, Jer Yuarn ; Tai, E. Shyong ; Lin, Xu ; Miki, Tetsuro ; Kim, Bong Jo ; Takeuchi, Fumihiko ; Zheng, Wei ; Shu, Xiao Ou. / Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference. In: Scientific reports. 2016 ; Vol. 6.

@article{153cda8f41134cc48b01d3f9083e8c13,

title = "Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference",

abstract = "Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.",

author = "Wanqing Wen and Norihiro Kato and Hwang, {Joo Yeon} and Xingyi Guo and Yasuharu Tabara and Huaixing Li and Rajkumar Dorajoo and Xiaobo Yang and Tsai, {Fuu Jen} and Shengxu Li and Ying Wu and Tangchun Wu and Soriul Kim and Xiuqing Guo and Jun Liang and Dmitry Shungin and Adair, {Linda S.} and Koichi Akiyama and Matthew Allison and Qiuyin Cai and Chang, {Li Ching} and Chen, {Chien Hsiun} and Chen, {Yuan Tsong} and Cho, {Yoon Shin} and Choi, {Bo Youl} and Yutang Gao and Go, {Min Jin} and Dongfeng Gu and Han, {Bok Ghee} and Meian He and Hixson, {James E.} and Yanling Hu and Tao Huang and Masato Isono and Jung, {Keum Ji} and Daehee Kang and Kim, {Young Jin} and Yoshikuni Kita and Juyoung Lee and Lee, {Nanette R.} and Jeannette Lee and Yiqin Wang and Liu, {Jian Jun} and Jirong Long and Sanghoon Moon and Yasuyuki Nakamura and Masahiro Nakatochi and Keizo Ohnaka and Dabeeru Rao and Jiajun Shi and Sull, {Jae Woong} and Aihua Tan and Hirotsugu Ueshima and Chen Wu and Xiang, {Yong Bing} and Ken Yamamoto and Jie Yao and Xingwang Ye and Mitsuhiro Yokota and Xiaomin Zhang and Yan Zheng and Lu Qi and Rotter, {Jerome I.} and Jee, {Sun Ha} and Dongxin Lin and Mohlke, {Karen L.} and Jiang He and Zengnan Mo and Wu, {Jer Yuarn} and Tai, {E. Shyong} and Xu Lin and Tetsuro Miki and Kim, {Bong Jo} and Fumihiko Takeuchi and Wei Zheng and Shu, {Xiao Ou}",

note = "Funding Information: The authors for this work would like to thank the Genetic Investigation of ANthropometric Traits (GIANT) consortium for providing unpublished data for replication of the study findings. The Shanghai Genome Wide Associations Studies (SGWAS) would like to thank the dedicated investigators and staff members from the research teams at Vanderbilt University, the Shanghai Cancer Institute, and the Shanghai Institute of Preventive Medicine, and most of all, the study participants for their contributions to the studies. The CLHNS investigators thank the Office of Population Studies Foundation research and data collection teams for CLHNS and the Mammalian Genotyping Core at University of North Carolina at Chapel Hill. This work was supported by the National Institutes of Health. Genotyping assays and statistical analyses for the SGWAS were supported primarily by NIH grants [R01 CA064277, R37 CA70867, R01 CA090899, R01 CA118229, and R01 CA122756]; and by the Ingram professorship funds, Allen Foundation funds, and Vanderbilt CTSA grant from NCRR/NIH [1 UL1 RR024975]. Grant support for the participating studies includes: the Shanghai Breast Cancer Study [R01 CA064277]; the Shanghai Women{\textquoteright}s Health Study [R37 CA70867]; the Shanghai Breast Cancer Survival Study [R01 CA118229]; the Shanghai Endometrial Cancer Study [R01 CA092585]; and the Shanghai Men{\textquoteright}s Health Study [UM1 CA173640]. The NHAPC study was supported by the National Natural Science Foundation of China [30930081, 81321062]; the National Key Basic Research Program of Ministry of Science and Technology [2012CB524905; and the Knowledge Innovation Program of the Chinese Academy of Sciences [KSCX2-EW-R-10]. The Cardio-metabolic Genome Epidemiology (CAGE) studies were supported by Grants for Scientific Research – Priority Areas “Medical Genome Science (Millennium Genome Project)” and “Applied Genomics” [20018020, 18018030, 12204008]; Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan [24390084, 25293141, 23659352, 23659382, 21390099, 20390185, 19659163, 16790336, 11694285, 17390186, 20390184, and 24390165]; a Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare, Japan [H15-Longevity, H15-genome, H17-longevity, H16-kenko, H18-longevity (kokusai)]; a Science and Technology Incubation Program in Advanced Regions, Japan Science and Technology Agency; National Cardiovascular Research Grants; Research grant from the Japan Atherosclerosis Prevention Found; Research grant from Ehime University. The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) was supported by research grants from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland [U01HL072507, R01HL087263, and R01HL090682]. The Korea Genome Wide Association Studies, which includes four projects: KARE, HEXA, the Health2 cohort, and CAVAS, were supported by grants from the Korea Centers for Disease Control and Prevention (4845-301, 4851-302 and 4851-307) and an intramural grant from the Korea National Institute of Health (2012-N73002-00); The KARE project was supported by grants from the Korea Centers for Disease Control and Prevention (4845-301, 4851-302 and 4851-307) and an intramural grant from the KoreaNational Institute of Health (2012-N73002-00), the Republic of Korea. The Korean Cancer Prevention Study-II (KCPS-II) was supported by a grant from the National R&D Program for Cancer Control; Ministry for Health, Welfare and Family Affairs, Republic of Korea [1220180]. The Singapore Prospective Study program was funded by the Biomedical Research Council of Singapore under the individual research grants scheme; and the National Medical Research Council of Singapore under the clinician scientist award scheme. The Cebu Longitudinal Health and Nutrition Survey (CLHNS) was supported by National Institutes of Health grants [DK078150, TW05596, HL085144, TW008288]; and pilot funds [RR20649, ES10126, and DK56350].",

year = "2016",

month = jan,

day = "20",

doi = "10.1038/srep17958",

language = "English",

volume = "6",

journal = "Scientific Reports",

issn = "2045-2322",

}

Wen, W, Kato, N, Hwang, JY, Guo, X, Tabara, Y, Li, H, Dorajoo, R, Yang, X, Tsai, FJ, Li, S, Wu, Y, Wu, T, Kim, S, Guo, X, Liang, J, Shungin, D, Adair, LS, Akiyama, K, Allison, M, Cai, Q, Chang, LC, Chen, CH, Chen, YT, Cho, YS, Choi, BY, Gao, Y, Go, MJ, Gu, D, Han, BG, He, M, Hixson, JE, Hu, Y, Huang, T, Isono, M, Jung, KJ, Kang, D, Kim, YJ, Kita, Y, Lee, J, Lee, NR, Lee, J, Wang, Y, Liu, JJ, Long, J, Moon, S, Nakamura, Y, Nakatochi, M, Ohnaka, K, Rao, D, Shi, J, Sull, JW, Tan, A, Ueshima, H, Wu, C, Xiang, YB, Yamamoto, K, Yao, J, Ye, X, Yokota, M, Zhang, X, Zheng, Y, Qi, L, Rotter, JI, Jee, SH, Lin, D, Mohlke, KL, He, J, Mo, Z, Wu, JY, Tai, ES, Lin, X, Miki, T, Kim, BJ, Takeuchi, F, Zheng, W & Shu, XO 2016, 'Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference', Scientific reports, vol. 6, 17958. https://doi.org/10.1038/srep17958

Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference. / Wen, Wanqing; Kato, Norihiro; Hwang, Joo Yeon; Guo, Xingyi; Tabara, Yasuharu; Li, Huaixing; Dorajoo, Rajkumar; Yang, Xiaobo; Tsai, Fuu Jen; Li, Shengxu; Wu, Ying; Wu, Tangchun; Kim, Soriul; Guo, Xiuqing; Liang, Jun; Shungin, Dmitry; Adair, Linda S.; Akiyama, Koichi; Allison, Matthew; Cai, Qiuyin; Chang, Li Ching; Chen, Chien Hsiun; Chen, Yuan Tsong; Cho, Yoon Shin; Choi, Bo Youl; Gao, Yutang; Go, Min Jin; Gu, Dongfeng; Han, Bok Ghee; He, Meian; Hixson, James E.; Hu, Yanling; Huang, Tao; Isono, Masato; Jung, Keum Ji; Kang, Daehee; Kim, Young Jin; Kita, Yoshikuni; Lee, Juyoung; Lee, Nanette R.; Lee, Jeannette; Wang, Yiqin; Liu, Jian Jun; Long, Jirong; Moon, Sanghoon; Nakamura, Yasuyuki; Nakatochi, Masahiro; Ohnaka, Keizo; Rao, Dabeeru; Shi, Jiajun; Sull, Jae Woong; Tan, Aihua; Ueshima, Hirotsugu; Wu, Chen; Xiang, Yong Bing; Yamamoto, Ken; Yao, Jie; Ye, Xingwang; Yokota, Mitsuhiro; Zhang, Xiaomin; Zheng, Yan; Qi, Lu; Rotter, Jerome I.; Jee, Sun Ha; Lin, Dongxin; Mohlke, Karen L.; He, Jiang; Mo, Zengnan; Wu, Jer Yuarn; Tai, E. Shyong; Lin, Xu; Miki, Tetsuro; Kim, Bong Jo; Takeuchi, Fumihiko; Zheng, Wei; Shu, Xiao Ou.

In: Scientific reports, Vol. 6, 17958, 20.01.2016.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference

AU - Wen, Wanqing

AU - Kato, Norihiro

AU - Hwang, Joo Yeon

AU - Guo, Xingyi

AU - Tabara, Yasuharu

AU - Li, Huaixing

AU - Dorajoo, Rajkumar

AU - Yang, Xiaobo

AU - Tsai, Fuu Jen

AU - Li, Shengxu

AU - Wu, Ying

AU - Wu, Tangchun

AU - Kim, Soriul

AU - Guo, Xiuqing

AU - Liang, Jun

AU - Shungin, Dmitry

AU - Adair, Linda S.

AU - Akiyama, Koichi

AU - Allison, Matthew

AU - Cai, Qiuyin

AU - Chang, Li Ching

AU - Chen, Chien Hsiun

AU - Chen, Yuan Tsong

AU - Cho, Yoon Shin

AU - Choi, Bo Youl

AU - Gao, Yutang

AU - Go, Min Jin

AU - Gu, Dongfeng

AU - Han, Bok Ghee

AU - He, Meian

AU - Hixson, James E.

AU - Hu, Yanling

AU - Huang, Tao

AU - Isono, Masato

AU - Jung, Keum Ji

AU - Kang, Daehee

AU - Kim, Young Jin

AU - Kita, Yoshikuni

AU - Lee, Juyoung

AU - Lee, Nanette R.

AU - Lee, Jeannette

AU - Wang, Yiqin

AU - Liu, Jian Jun

AU - Long, Jirong

AU - Moon, Sanghoon

AU - Nakamura, Yasuyuki

AU - Nakatochi, Masahiro

AU - Ohnaka, Keizo

AU - Rao, Dabeeru

AU - Shi, Jiajun

AU - Sull, Jae Woong

AU - Tan, Aihua

AU - Ueshima, Hirotsugu

AU - Wu, Chen

AU - Xiang, Yong Bing

AU - Yamamoto, Ken

AU - Yao, Jie

AU - Ye, Xingwang

AU - Yokota, Mitsuhiro

AU - Zhang, Xiaomin

AU - Zheng, Yan

AU - Qi, Lu

AU - Rotter, Jerome I.

AU - Jee, Sun Ha

AU - Lin, Dongxin

AU - Mohlke, Karen L.

AU - He, Jiang

AU - Mo, Zengnan

AU - Wu, Jer Yuarn

AU - Tai, E. Shyong

AU - Lin, Xu

AU - Miki, Tetsuro

AU - Kim, Bong Jo

AU - Takeuchi, Fumihiko

AU - Zheng, Wei

AU - Shu, Xiao Ou

N1 - Funding Information: The authors for this work would like to thank the Genetic Investigation of ANthropometric Traits (GIANT) consortium for providing unpublished data for replication of the study findings. The Shanghai Genome Wide Associations Studies (SGWAS) would like to thank the dedicated investigators and staff members from the research teams at Vanderbilt University, the Shanghai Cancer Institute, and the Shanghai Institute of Preventive Medicine, and most of all, the study participants for their contributions to the studies. The CLHNS investigators thank the Office of Population Studies Foundation research and data collection teams for CLHNS and the Mammalian Genotyping Core at University of North Carolina at Chapel Hill. This work was supported by the National Institutes of Health. Genotyping assays and statistical analyses for the SGWAS were supported primarily by NIH grants [R01 CA064277, R37 CA70867, R01 CA090899, R01 CA118229, and R01 CA122756]; and by the Ingram professorship funds, Allen Foundation funds, and Vanderbilt CTSA grant from NCRR/NIH [1 UL1 RR024975]. Grant support for the participating studies includes: the Shanghai Breast Cancer Study [R01 CA064277]; the Shanghai Women’s Health Study [R37 CA70867]; the Shanghai Breast Cancer Survival Study [R01 CA118229]; the Shanghai Endometrial Cancer Study [R01 CA092585]; and the Shanghai Men’s Health Study [UM1 CA173640]. The NHAPC study was supported by the National Natural Science Foundation of China [30930081, 81321062]; the National Key Basic Research Program of Ministry of Science and Technology [2012CB524905; and the Knowledge Innovation Program of the Chinese Academy of Sciences [KSCX2-EW-R-10]. The Cardio-metabolic Genome Epidemiology (CAGE) studies were supported by Grants for Scientific Research – Priority Areas “Medical Genome Science (Millennium Genome Project)” and “Applied Genomics” [20018020, 18018030, 12204008]; Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology, Japan [24390084, 25293141, 23659352, 23659382, 21390099, 20390185, 19659163, 16790336, 11694285, 17390186, 20390184, and 24390165]; a Health and Labor Sciences Research Grants from the Ministry of Health, Labor and Welfare, Japan [H15-Longevity, H15-genome, H17-longevity, H16-kenko, H18-longevity (kokusai)]; a Science and Technology Incubation Program in Advanced Regions, Japan Science and Technology Agency; National Cardiovascular Research Grants; Research grant from the Japan Atherosclerosis Prevention Found; Research grant from Ehime University. The Genetic Epidemiology Network of Salt Sensitivity (GenSalt) was supported by research grants from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland [U01HL072507, R01HL087263, and R01HL090682]. The Korea Genome Wide Association Studies, which includes four projects: KARE, HEXA, the Health2 cohort, and CAVAS, were supported by grants from the Korea Centers for Disease Control and Prevention (4845-301, 4851-302 and 4851-307) and an intramural grant from the Korea National Institute of Health (2012-N73002-00); The KARE project was supported by grants from the Korea Centers for Disease Control and Prevention (4845-301, 4851-302 and 4851-307) and an intramural grant from the KoreaNational Institute of Health (2012-N73002-00), the Republic of Korea. The Korean Cancer Prevention Study-II (KCPS-II) was supported by a grant from the National R&D Program for Cancer Control; Ministry for Health, Welfare and Family Affairs, Republic of Korea [1220180]. The Singapore Prospective Study program was funded by the Biomedical Research Council of Singapore under the individual research grants scheme; and the National Medical Research Council of Singapore under the clinician scientist award scheme. The Cebu Longitudinal Health and Nutrition Survey (CLHNS) was supported by National Institutes of Health grants [DK078150, TW05596, HL085144, TW008288]; and pilot funds [RR20649, ES10126, and DK56350].

PY - 2016/1/20

Y1 - 2016/1/20

N2 - Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.

AB - Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3, CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.

UR - http://www.scopus.com/inward/record.url?scp=84955278775&partnerID=8YFLogxK

U2 - 10.1038/srep17958

DO - 10.1038/srep17958

M3 - Article

C2 - 26785701

AN - SCOPUS:84955278775

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 17958

ER -

Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference

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