HLA-B∗07, HLA-DRB1∗07, HLA-DRB1∗12, and HLA-c∗03:02 strongly associate with BMI: Data from 1.3 million healthy Chinese adults

Jie Shen; Tingwei Guo; Tao Wang; Yisong Zhen; Xiao Ma; Yuan Wang; Zhi Xin Zhang; Jian Ping Cai; Wei Mao; Fa Ming Zhu; Jian Ping Li; Zhen Lei Wang; De Mei Zhang; Meng Li Liu; Xiao Yan Shan; Bo Wei Zhang; Chuan Fu Zhu; Zhi Hui Deng; Wei Jian Yu; Qiang Chen; Guo Liang Li; Tao Yang; Shan Lu; Qin Qin Pan; Su Fan; Xiao Yan Wang; Xing Zhao; Xin Yun Bi; Yan Hui Qiao; Pin Can Su; Rong Lv; Guo Ying Li; Heng Cong Li; Bin Pei; Li Xin Jiao; Gang Shen; Jie Liu; Zhi Hui Feng; Yu Ping Su; Yu Bin Xie; Wen Ying Di; Xin Yu Wang; Xiang Liu; Xiao Ping Zhang; Dan Du; Qi Liu; Ying Han; Jia Wei Chen; Min Gu; Leslie J. Baier

doi:10.2337/db17-0852

HLA-B^∗07, HLA-DRB1^∗07, HLA-DRB1^∗12, and HLA-c^∗03:02 strongly associate with BMI: Data from 1.3 million healthy Chinese adults

Jie Shen, Tingwei Guo, Tao Wang, Yisong Zhen, Xiao Ma, Yuan Wang, Zhi Xin Zhang, Jian Ping Cai, Wei Mao, Fa Ming Zhu, Jian Ping Li, Zhen Lei Wang, De Mei Zhang, Meng Li Liu, Xiao Yan Shan, Bo Wei Zhang, Chuan Fu Zhu, Zhi Hui Deng, Wei Jian Yu, Qiang ChenGuo Liang Li, Tao Yang, Shan Lu, Qin Qin Pan, Su Fan, Xiao Yan Wang, Xing Zhao, Xin Yun Bi, Yan Hui Qiao, Pin Can Su, Rong Lv, Guo Ying Li, Heng Cong Li, Bin Pei, Li Xin Jiao, Gang Shen, Jie Liu, Zhi Hui Feng, Yu Ping Su, Yu Bin Xie, Wen Ying Di, Xin Yu Wang, Xiang Liu, Xiao Ping Zhang, Dan Du, Qi Liu, Ying Han, Jia Wei Chen, Min Gu, Leslie J. Baier

Epidemiology & Population Health

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5 Scopus citations

Abstract

Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 highresolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B^∗07, DRB1^∗07, DRB1^∗12, and C^∗03:02 provided the strongest associations with BMI (P = 6.89 × 10^-10, 1.32 × 10^-9, 1.52 × 10^-9, and 4.45 × 10^-8, respectively), where B^∗07 and DRB1^∗07 also had evidence for sex-specific effects (P_{heterogeneity} = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novelbiological connection between HLA alleles and obesity.

Original language	English (US)
Pages (from-to)	861-871
Number of pages	11
Journal	Diabetes
Volume	67
Issue number	5
DOIs	https://doi.org/10.2337/db17-0852
State	Published - May 1 2018

ASJC Scopus subject areas

Internal Medicine
Endocrinology, Diabetes and Metabolism

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Shen, J., Guo, T., Wang, T., Zhen, Y., Ma, X., Wang, Y., Zhang, Z. X., Cai, J. P., Mao, W., Zhu, F. M., Li, J. P., Wang, Z. L., Zhang, D. M., Liu, M. L., Shan, X. Y., Zhang, B. W., Zhu, C. F., Deng, Z. H., Yu, W. J., ... Baier, L. J. (2018). HLA-B^∗07, HLA-DRB1^∗07, HLA-DRB1^∗12, and HLA-c^∗03:02 strongly associate with BMI: Data from 1.3 million healthy Chinese adults. Diabetes, 67(5), 861-871. https://doi.org/10.2337/db17-0852

Shen, J, Guo, T, Wang, T, Zhen, Y, Ma, X, Wang, Y, Zhang, ZX, Cai, JP, Mao, W, Zhu, FM, Li, JP, Wang, ZL, Zhang, DM, Liu, ML, Shan, XY, Zhang, BW, Zhu, CF, Deng, ZH, Yu, WJ, Chen, Q, Li, GL, Yang, T, Lu, S, Pan, QQ, Fan, S, Wang, XY, Zhao, X, Bi, XY, Qiao, YH, Su, PC, Lv, R, Li, GY, Li, HC, Pei, B, Jiao, LX, Shen, G, Liu, J, Feng, ZH, Su, YP, Xie, YB, Di, WY, Wang, XY, Liu, X, Zhang, XP, Du, D, Liu, Q, Han, Y, Chen, JW, Gu, M & Baier, LJ 2018, 'HLA-B^∗07, HLA-DRB1^∗07, HLA-DRB1^∗12, and HLA-c^∗03:02 strongly associate with BMI: Data from 1.3 million healthy Chinese adults', Diabetes, vol. 67, no. 5, pp. 861-871. https://doi.org/10.2337/db17-0852

@article{72ac7bb9a67a4b618d23be0f866fbae5,

title = "HLA-B∗07, HLA-DRB1∗07, HLA-DRB1∗12, and HLA-c∗03:02 strongly associate with BMI: Data from 1.3 million healthy Chinese adults",

abstract = "Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 highresolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B∗07, DRB1∗07, DRB1∗12, and C∗03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B∗07 and DRB1∗07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novelbiological connection between HLA alleles and obesity.",

author = "Jie Shen and Tingwei Guo and Tao Wang and Yisong Zhen and Xiao Ma and Yuan Wang and Zhang, {Zhi Xin} and Cai, {Jian Ping} and Wei Mao and Zhu, {Fa Ming} and Li, {Jian Ping} and Wang, {Zhen Lei} and Zhang, {De Mei} and Liu, {Meng Li} and Shan, {Xiao Yan} and Zhang, {Bo Wei} and Zhu, {Chuan Fu} and Deng, {Zhi Hui} and Yu, {Wei Jian} and Qiang Chen and Li, {Guo Liang} and Tao Yang and Shan Lu and Pan, {Qin Qin} and Su Fan and Wang, {Xiao Yan} and Xing Zhao and Bi, {Xin Yun} and Qiao, {Yan Hui} and Su, {Pin Can} and Rong Lv and Li, {Guo Ying} and Li, {Heng Cong} and Bin Pei and Jiao, {Li Xin} and Gang Shen and Jie Liu and Feng, {Zhi Hui} and Su, {Yu Ping} and Xie, {Yu Bin} and Di, {Wen Ying} and Wang, {Xin Yu} and Xiang Liu and Zhang, {Xiao Ping} and Dan Du and Qi Liu and Ying Han and Chen, {Jia Wei} and Min Gu and Baier, {Leslie J.}",

note = "Funding Information: Acknowledgments. The authors thank Dr. Bernice Morrow, Department of Genetics, Albert Einstein College of Medicine, and Dr. Enpeng Zhao, Department of Medicine, Albert Einstein College of Medicine, for critical comments and suggestions for discussion. All of the data are from the CMDP. Funding. This work was supported by grants from the CMDP (Grant No. 2011001), the Jiangsu Province Administration of Traditional Chinese Medicine (Grant No. LZ1320), and the Foundation of Jiangsu Health Committee and the State Key Laboratory of Natural Medicines of China Pharmaceutical University (Grant No. SKLNMZZ 20210F). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. J.S. and T.G. conceived the study and contributed to the study design and analysis strategy. J.S., T.G., T.W., Y.Z., and Y.W. conducted all analyses. J.S., T.G., and L.J.B. wrote the manuscript. X.M., Z.-X.Z., J.-P.C., W.M., F.-M.Z., J.-P.L., Z.-L.W., D.-M.Z., M.-L.L., X.-Y.S., B.-W.Z., C.-F.Z., Z.-H.D., W.-J.Y., Q.C., G.-L.L., T.Y., S.L., Q.-Q.P., S.F., Xia.-Y.W., X.Z., X.-Y.B., Y.-H.Q., P.-C.S., R.L., G.-Y.L., H.-C.L., B.P., L.-X.J., G.S., J.L., Z.-H.F., Y.-P.S., Y.-B.X., W.-Y.D., Xin-Y.W., X.L., X.-P.Z., D.D., Q.L., and Y.H. contributed primarily to sample collection and/or HLA genotyping. J.-W.C. and M.G. contributed to critical writing and review of the manuscript. All authors contributed to the final manuscript. J.S. and T.G. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the analysis. Publisher Copyright: {\textcopyright} 2018 by the American Diabetes Association.",

year = "2018",

month = may,

day = "1",

doi = "10.2337/db17-0852",

language = "English (US)",

volume = "67",

pages = "861--871",

journal = "Diabetes",

issn = "0012-1797",

publisher = "American Diabetes Association Inc.",

number = "5",

}

TY - JOUR

T1 - HLA-B∗07, HLA-DRB1∗07, HLA-DRB1∗12, and HLA-c∗03:02 strongly associate with BMI

T2 - Data from 1.3 million healthy Chinese adults

AU - Shen, Jie

AU - Guo, Tingwei

AU - Wang, Tao

AU - Zhen, Yisong

AU - Ma, Xiao

AU - Wang, Yuan

AU - Zhang, Zhi Xin

AU - Cai, Jian Ping

AU - Mao, Wei

AU - Zhu, Fa Ming

AU - Li, Jian Ping

AU - Wang, Zhen Lei

AU - Zhang, De Mei

AU - Liu, Meng Li

AU - Shan, Xiao Yan

AU - Zhang, Bo Wei

AU - Zhu, Chuan Fu

AU - Deng, Zhi Hui

AU - Yu, Wei Jian

AU - Chen, Qiang

AU - Li, Guo Liang

AU - Yang, Tao

AU - Lu, Shan

AU - Pan, Qin Qin

AU - Fan, Su

AU - Wang, Xiao Yan

AU - Zhao, Xing

AU - Bi, Xin Yun

AU - Qiao, Yan Hui

AU - Su, Pin Can

AU - Lv, Rong

AU - Li, Guo Ying

AU - Li, Heng Cong

AU - Pei, Bin

AU - Jiao, Li Xin

AU - Shen, Gang

AU - Liu, Jie

AU - Feng, Zhi Hui

AU - Su, Yu Ping

AU - Xie, Yu Bin

AU - Di, Wen Ying

AU - Wang, Xin Yu

AU - Liu, Xiang

AU - Zhang, Xiao Ping

AU - Du, Dan

AU - Liu, Qi

AU - Han, Ying

AU - Chen, Jia Wei

AU - Gu, Min

AU - Baier, Leslie J.

N1 - Funding Information: Acknowledgments. The authors thank Dr. Bernice Morrow, Department of Genetics, Albert Einstein College of Medicine, and Dr. Enpeng Zhao, Department of Medicine, Albert Einstein College of Medicine, for critical comments and suggestions for discussion. All of the data are from the CMDP. Funding. This work was supported by grants from the CMDP (Grant No. 2011001), the Jiangsu Province Administration of Traditional Chinese Medicine (Grant No. LZ1320), and the Foundation of Jiangsu Health Committee and the State Key Laboratory of Natural Medicines of China Pharmaceutical University (Grant No. SKLNMZZ 20210F). Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. J.S. and T.G. conceived the study and contributed to the study design and analysis strategy. J.S., T.G., T.W., Y.Z., and Y.W. conducted all analyses. J.S., T.G., and L.J.B. wrote the manuscript. X.M., Z.-X.Z., J.-P.C., W.M., F.-M.Z., J.-P.L., Z.-L.W., D.-M.Z., M.-L.L., X.-Y.S., B.-W.Z., C.-F.Z., Z.-H.D., W.-J.Y., Q.C., G.-L.L., T.Y., S.L., Q.-Q.P., S.F., Xia.-Y.W., X.Z., X.-Y.B., Y.-H.Q., P.-C.S., R.L., G.-Y.L., H.-C.L., B.P., L.-X.J., G.S., J.L., Z.-H.F., Y.-P.S., Y.-B.X., W.-Y.D., Xin-Y.W., X.L., X.-P.Z., D.D., Q.L., and Y.H. contributed primarily to sample collection and/or HLA genotyping. J.-W.C. and M.G. contributed to critical writing and review of the manuscript. All authors contributed to the final manuscript. J.S. and T.G. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the analysis. Publisher Copyright: © 2018 by the American Diabetes Association.

PY - 2018/5/1

Y1 - 2018/5/1

N2 - Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 highresolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B∗07, DRB1∗07, DRB1∗12, and C∗03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B∗07 and DRB1∗07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novelbiological connection between HLA alleles and obesity.

AB - Strong associations between HLA alleles and infectious and autoimmune diseases are well established. Although obesity is also associated with these diseases, the relationship between HLA and obesity has not been systematically investigated in a large cohort. In the current study, we analyzed the association of HLA alleles with BMI using data from 1.3 million healthy adult donors from the Chinese Marrow Donor Program (CMDP). We found 23 HLA alleles, including 12 low-resolution and 11 highresolution alleles, were significantly associated with BMI after correction for multiple testing. Alleles associated with high BMI were enriched in haplotypes that were common in both Chinese and European populations, whereas the alleles associated with low BMI were enriched in haplotypes common only in Asians. Alleles B∗07, DRB1∗07, DRB1∗12, and C∗03:02 provided the strongest associations with BMI (P = 6.89 × 10-10, 1.32 × 10-9, 1.52 × 10-9, and 4.45 × 10-8, respectively), where B∗07 and DRB1∗07 also had evidence for sex-specific effects (Pheterogeneity = 0.0067 and 0.00058, respectively). These results, which identify associations between alleles of HLA-B, DRB1, and C with BMI in Chinese young adults, implicate a novelbiological connection between HLA alleles and obesity.

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UR - http://www.scopus.com/inward/citedby.url?scp=85046008629&partnerID=8YFLogxK

U2 - 10.2337/db17-0852

DO - 10.2337/db17-0852

M3 - Article

C2 - 29483183

AN - SCOPUS:85046008629

VL - 67

SP - 861

EP - 871

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 5

ER -

HLA-B^∗07, HLA-DRB1^∗07, HLA-DRB1^∗12, and HLA-c^∗03:02 strongly associate with BMI: Data from 1.3 million healthy Chinese adults

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