Department of Human Genetics, Faculty of Biomedical Sciences and Technology, Sri Ramachandra Institute of Higher Education and Research (Deemed to be University), Chennai, India.
Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley, Brownsville, TX, United States.
Front Endocrinol (Lausanne). 2022 Apr 14;13:847692. doi: 10.3389/fendo.2022.847692. eCollection 2022.
To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ≤ 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits.
为了评估 2 型糖尿病（T2D）的负担及其在印度内婚群体中的遗传特征，由于数据匮乏，我们旨在使用来自三个不同内婚种族群体（EEG）的基于家庭的队列来确定 T2D 的患病率，并估计其遗传率。这些 EEG 分别代表印度北部（拉贾斯坦邦[阿加瓦尔人：AG]）和南部（泰米尔纳德邦[切蒂人：CH]和安得拉邦[雷迪人：RE]）。为了进行比较，我们还使用了以前从另一个印度北部旁遮普锡克人（SI）EEG 收集的基于家庭的数据集。此外，我们还检查了各种与 T2D 相关的心脏代谢特征，并确定了它们的遗传率。这些研究是作为印度糖尿病遗传研究的一部分与美国（INDIGENIUS）联盟合作进行的。CH、AG 和 RE EEG 收集了系谱、人口统计学、表型、协变量数据和样本。T2D 的状态根据 ADA 指南定义（空腹血糖≥126mg/dl 或 HbA1c≥6.5%和/或使用糖尿病药物/病史）。CH（N=517，家庭=21，平均年龄=47y，平均 BMI=27）、AG（N=530，家庭=25，平均年龄=43y，平均 BMI=27）和 RE（N=500，家庭=22，平均年龄=46y，平均 BMI=27）的 T2D 患病率分别为 33%、37%和 36%。此外，这些 EEG 中的研究参与者被发现存在增加的心脏代谢风险（例如肥胖和糖尿病前期）。以前还获得了 SI EEG（N=1260，家庭=324，年龄=51y，BMI=27，T2D=75%）的类似特征。我们使用方差分量方法在调整协变量效应后进行遗传分析。CH、RE、SI 和 AG 中 T2D 的遗传率（h）估计值分别为 30%、46%、54%和 82%，且具有统计学意义（P≤0.05）。AG、CH 和 RE EEG 中其他与 T2D 相关的特征（例如 BMI、脂质、血压）表现出强烈的加性遗传影响（h 范围：17%[甘油三酯/AG 和 hs-CRP/RE]-86%[血糖/非 T2D/AG]）。我们的研究结果强调了 T2D 在印度 EEG 中的高负担，以及对 T2D 和相关特征的显著和差异加性遗传影响。
