Dataset Information

HLA-B07, HLA-DRB107, HLA-DRB112, and HLA-C03:02 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 high-resolution 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 novel biological connection between HLA alleles and obesity.

SUBMITTER: Shen J

PROVIDER: S-EPMC6463754 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

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HLA-B07, HLA-DRB107, HLA-DRB112, and HLA-C03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

Shen Jie J Guo Tingwei T Wang Tao T Zhen Yisong Y Ma Xiao X Wang Yuan Y Zhang Zhi-Xin ZX Cai Jian-Ping JP Mao Wei W Zhu Fa-Ming FM Li Jian-Ping JP Wang Zhen-Lei ZL Zhang De-Mei DM Liu Meng-Li ML Shan Xiao-Yan XY Zhang Bo-Wei BW Zhu Chuan-Fu CF Deng Zhi-Hui ZH Yu Wei-Jian WJ Chen Qiang Q Li Guo-Liang GL Yang Tao T Lu Shan S Pan Qin-Qin QQ Fan Su S Wang Xiao-Yan XY Zhao Xing X Bi Xin-Yun XY Qiao Yan-Hui YH Su Pin-Can PC Lv Rong R Li Guo-Ying GY Li Heng-Cong HC Pei Bin B Jiao Li-Xin LX Shen Gang G Liu Jie J Feng Zhi-Hui ZH Su Yu-Ping YP Xie Yu-Bin YB Di Wen-Ying WY Wang Xin-Yu XY Liu Xiang X Zhang Xiao-Ping XP Du Dan D Liu Qi Q Han Ying Y Chen Jia-Wei JW Gu Min M Baier Leslie J LJ

Diabetes 20180226 5

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 high-resolut ...[more]

PMID: 29483183

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Project description:Background and objectivesTo study human leukocyte antigen (HLA) allele associations in anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis.MethodsA multiethnic cohort of 269 patients with anti-LGI1 encephalitis and 1,359 controls was included. Four-digit HLA sequencing and genome wide association single-nucleotide polymorphism typing imputation (0.99 concordance) were used for HLA typing. Significance of primary and secondary associations was tested using χ2, Fisher exact tests, or logistic regression with the control of population stratification covariates when applicable.ResultsDRB1*07:01 and DQA1*02:01, 2 alleles in strong linkage disequilibrium, were associated with the disease (90% vs 24%, OR = 27.8, p < 10e-50) across ethnicity independent of variation at DRB3 and DQB1, 2 flanking HLA loci. DRB1*07:01 homozygosity was associated with a doubling of risk (OR = 2.1, p = 0.010), suggesting causality. DRB1*07:01 negative subjects were younger (p = 0.003) and more frequently female (p = 0.015). Three patients with malignant thymomas did not carry DRB1*07:01, whereas patients with other tumors had high DRB1*07:01 frequency, suggesting that the presence of tumors other than thymomas may be coincidental and not causal. In both DRB1*07:01 heterozygous individuals and DRB1*07:01 negative subjects, DRB1*04:02 was associated with anti-LGI1 encephalitis, indicating an independent effect of this allele (OR = 6.85, p = 4.57 × 10-6 and OR = 8.93, p = 2.50 × 10-3, respectively). DRB1*04:02 was also independently associated with younger age at onset (β = -6.68, p = 9.78 × 10-3). Major histocompatibility complex peptide-binding predictions using LGI1-derived peptides revealed divergent binding propensities for DRB1*04:02 and DRB1*07:01 alleles, suggesting independent pathogenic mechanisms.DiscussionIn addition to the established primary DRB1*07:01 association in anti-LGI1 encephalitis, we observe a secondary effect of DRB1*04:02 with lower age at onset. Our study provides evidence for secondary effects within HLA locus that correlate with clinical phenotypes in anti-LGI1 encephalitis.

Dataset Information

HLA-B07, HLA-DRB107, HLA-DRB112, and HLA-C03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

Publications

HLA-B07, HLA-DRB107, HLA-DRB112, and HLA-C03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

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Dataset Information

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.

Publications

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.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

HLA-B07, HLA-DRB107, HLA-DRB112, and HLA-C03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.

HLA-B07, HLA-DRB107, HLA-DRB112, and HLA-C03:02 Strongly Associate With BMI: Data From 1.3 Million Healthy Chinese Adults.