Longevity
Research on longevity, which can also be thought of as maximal lifespan, is more popularly associated with extending human life than with the more strict connotation of life expectancy (more at Wikipedia). Heredity and other factors (such as birth order and age of the mother at the time of the person's birth) influence longevity. [1]
There are at least 3 potentially overlapping classes of SNPs (or other genetic polymorphisms) that can be considered to affect longevity. First, many SNPs may influence susceptibility to diseases that shorten longevity; these can be found in SNPedia associated with those diseases, and related information is summarized on the heritability page. Second, some SNPs are being discovered based on their prevalence in people who live beyond average human lifespan; these SNPs may enhance longevity. Third, certain SNPs may be to able to affect longevity only in certain environmental contexts, for example SNPs that shorten or lengthen longevity only if an individual with a given genotype is also exposed to certain diets or toxins (such as cigarette smoke).
SNPs from the latter two categories include:
- rs2802292, in the FOXO3 gene, associated with Japanese male centarians
- rs1935949, only correlated in women with longevity
- rs3758391, in the SIRT1 gene, associated with longevity/cognitive health
- rs5882, in the CETP gene, associated with longevity/cognitive health
- rs1042522, a SNP in the TP53 gene, associated with a lifespan difference of 3 years
- rs1800795, a SNP in the IL6 gene, seen in a study of ~100 nonagenarians
- rs2811712, a SNP associated with risk for physical impairment in the elderly (indirectly, longevity)
- rs34516635, a SNP in the IGF1R gene, claimed to be of significance based on a study of centenarian Ashkenazi females
- rs2542052, a SNP near the APOC3 gene, was associated with longevity in a study of Ashkenazi who lived to at least age 95 [PMID 16602826]
- rs3803304, a SNP in the AKT1 gene, correlating in 3 cohorts
- rs1061170, a SNP in the CFH gene, in a 4 year study of longevity of 491 nonagenarians [PMID 19000922]
- rs6873545 or rs4590183, which tag the d3-GHR allele, which when homozygous (in males) associate with longevity
A 2017 GWAS analysis of parental longevity in 300,000 UK Biobank participants of European descent found 10+ SNPs to be associated with combined mothers' and fathers' attained age (and a few others just with paternal or maternal age); these 10+ SNPs and the longevity-associated allele were [PMID 29227965
]:
- rs602633(T); located between CLESR2 and PSRC1
- rs28383322(C); located between HLA-DRB1 and HLA-DQA1
- rs55730499(C); located in an intron of the LPA gene
- rs1556516(G); 9p21 region, which includes CDKN2B-AS1 (ANRIL) and CDKN2A/B
- rs7137828(C); near ATXN2
- rs1317286(A); CHRNA3/5
- rs17514846(T); located in an intron of FURIN
- rs429358(T); APOE
- rs1627804(C)
- rs7844965(G); located in an intron of EPHX2
- rs61978928(T); located in the 3’ UTR of PROX2
- rs28926173(G)
- rs146254978(T)
- rs139137459(G)
Overall, it's useful to realize that SNPs are likely to influence your risk of dying from 9 of the top 10 causes of death (in developed countries), as noted below (based on 2000 US data):
- Heart disease (29.5% of deaths)
- Cancer (22.9%)
- Cerebrovascular disease (6.9%)
- Chronic lower respiratory disease (5.1%)
- Injury (3.9%; non-genetic)
- Diabetes (2.9%)
- Pneumonia/influenza (2.8%)
- Alzheimer's disease (2.0%)
- Kidney disease (1.6%)
- Septicemia (1.3%)
10.1126/science.1190532 identified 150 snps however numerous questions about the plausibility of the results, led to it's eventual retraction.
