A team from genetic testing firm MapmyGenome has found nine variants linked to longevity in the Indian population. At least one variant, the G allele of rs2802292 from the FOXO3A gene, has been found in populations in other countries.
The study appeared in NPJ Aging and was led by Sandhya Kiran Pemmasani, principal biostatistician at MapmyGenome.
Genetics of longevity are difficult to study. However, it is known genetics plays a major role—its influence is estimated to be around 25–40%. And, according to the latest estimates of the Longitudinal Aging Study in India, the country has the world’s second-largest number of older people, aged 60 and above.
For the study, long living individuals (LLIs), aged 85 and older, were compared with younger controls, aged 18–49 years, using data from GenomegaDB, a genetic database of Indians living in India.
The team used a proprietary chip with variants associated with multiple cancers, cardiovascular, neurological, gastro-intestinal, metabolic and auto-immune disorders.
Genotype data were generated using Illumina’s Infinium iSelect HTS Custom Genotyping BeadChip-24, which was developed by Mapmygenome. The chip has 10,133 probes corresponding to 8,768 unique variants associated with various phenotypes, like cancers, cardiovascular, neurological, gastrointestinal, metabolic and autoimmune disorders.
Cases were defined as individuals with self-reported age of greater than 85 years at the time of sample collection. Controls were the individuals with 18–49 years of age at the time of sample collection.
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.
Notably, the G allele of rs2802292 from the FOXO3A gene, associated with longevity in Japanese, German and French centenarians, was also found to be significant in this population.
Pathway enrichment analysis showed that the genes involved in oxidative stress, apoptosis, DNA damage repair, glucose metabolism and energy metabolism significantly affected longevity.
Longevity and healthy aging are influenced by various factors, like socioeconomic status, nutrition, lifestyle, physical activity, gender and genetics. Studies indicate that offspring of long-lived individuals tend to lead a healthy and longer life compared to the general population. This could be due to factors such as inheritance of genetic variants associated with healthy lipid profiles, enhanced insulin sensitivity, slower cognitive decline, and lower incidence of age-related diseases, like Alzheimer’s and cardiovascular diseases.
There is also a certain category of variants that are identified to be prevalent in long-living individuals through multiple genome-wide association studies (GWAS), candidate studies and meta-analyses related to longevity. They are the variants from Forkhead Box O3A (FOXO3A) and Apolipoprotein E (APOE) genes that are part of pathways associated with cell apoptosis, metabolism and oxidative stress. Variants that decrease the length of telomeres also influence an individual’s lifespan.
MapmyGenome aims to build on these findings by expanding the scope of its research to include other age-related conditions and exploring the interplay between genetics, environment, and lifestyle in shaping longevity.
“Our mission is to transform lives through genetics,” said Anuradha Acharya, founder and CEO of MapmyGenome. “This research reinforces our commitment to advancing scientific knowledge and empowering individuals with actionable insights for a healthier future.”
