Pemmasani Sandhya Kiran, R G Shakthiraju, V Suraj, Bhattacharyya Raunaq, Patel Chetan, Gupta Anil Kumar, Acharya Anuradha
Mapmygenome India Limited, Hyderabad, India.
SRISTI - Society for Research and Initiatives for Sustainable Technologies and Institutions, Ahmedabad, India.
NPJ Aging. 2024 Nov 20;10(1):51. doi: 10.1038/s41514-024-00179-9.
Genetic factors play a significant role in determining an individual's longevity. The present study was aimed at identifying genetic variants associated with longevity in Indian population. Long living individuals (LLIs), aged 85+, were compared with younger controls, aged 18-49 years, using data from GenomegaDB, a genetic database of Indians living in India. An in-house developed custom chip, having variants associated with various cancers, cardiovascular, neurological, gastro-intestinal, metabolic and auto-immune disorders, was used to generate genotype data. Logistic regression analysis with sex and top three genetic principal components as covariates resulted in 9 variants to be significantly associated with longevity at a p-value threshold of 5 × 10. Alleles associated with slower heart rate (rs365990, MYH6), decreased risk of osteoporosis and short body height (rs2982570, ESR1), decreased risk of schizophrenia (rs1339227, RIMS1-KCNQ5) and decreased risk of anxiety and neuroticism (rs391957, HSPA5) were found to have higher frequency in LLIs. Alleles associated with increased risk of atrial fibrillation (rs3903239, GORAB-PRRX1) and biliary disorders (rs2002042, ABCC2) were found to have lower frequency. The G allele of rs2802292 from FOXO3A gene, associated with longevity in Japanese, German and French centenarians, was also found to be significant in this population (P = 0.032). Pathway enrichment analysis revealed that the genes involved in oxidative stress, apoptosis, DNA damage repair, glucose metabolism and energy metabolism were significantly involved in affecting the longevity. Results of our study demonstrate the genetic basis of healthy aging and longevity in the population.
遗传因素在决定个体寿命方面起着重要作用。本研究旨在确定印度人群中与长寿相关的基因变异。利用来自GenomegaDB（一个居住在印度的印度人的基因数据库）的数据，将85岁及以上的长寿个体（LLIs）与18至49岁的年轻对照组进行比较。使用一种内部开发的定制芯片来生成基因型数据，该芯片具有与各种癌症、心血管、神经、胃肠、代谢和自身免疫性疾病相关的变异。以性别和前三个遗传主成分作为协变量进行逻辑回归分析，结果显示在p值阈值为5×10时，有9个变异与长寿显著相关。发现与心率减慢相关的等位基因（rs365990，MYH6）、骨质疏松症风险降低和身材矮小相关的等位基因（rs2982570，ESR1）、精神分裂症风险降低相关的等位基因（rs1339227，RIMS1-KCNQ5）以及焦虑和神经质风险降低相关的等位基因（rs391957，HSPA5）在LLIs中具有较高的频率。发现与心房颤动风险增加相关的等位基因（rs3903239，GORAB-PRRX1）和胆道疾病相关的等位基因（rs2002042，ABCC2）具有较低的频率。在日本、德国和法国的百岁老人中与长寿相关的FOXO3A基因的rs2802292的G等位基因在该人群中也具有显著性（P = 0.032）。通路富集分析表明，参与氧化应激、细胞凋亡、DNA损伤修复、葡萄糖代谢和能量代谢的基因在影响长寿方面具有显著作用。我们的研究结果证明了该人群健康衰老和长寿的遗传基础。
