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 | |
State | Published - Jan 20 2016 |
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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 -