Lifespan is a trait of enormous personal interest. Research into the biological basis of human lifespan, however, is hampered by the long time to death. Using a novel approach of regressing (272,081) parental lifespans beyond age 40 years on participant genotype in a new large data set (UK Biobank), we here show that common variants near the apolipoprotein E and nicotinic acetylcholine receptor subunit alpha 5 genes are associated with lifespan. The effects are strongly sex and age dependent, with APOE e4 differentially influencing maternal lifespan (P=4.2x10-15, effect -1.24 years of maternal life per imputed risk allele in parent; sex difference, P=0.011), and a locus near CHRNA3/5 differentially affecting paternal lifespan (P=4.8x10-11, effect -0.86 years per allele; sex difference P=0.075). Rare homozygous carriers of the risk alleles at both loci are predicted to have 3.3 3.7 years shorter lives.
Peter K. Joshi, et al. 2016 Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan. Nature Communications
Genetics of human lifespan ? heritability, association and prediction
The determinants of longevity are of wide interest and have been studied for over 100 years. Human lifespan is influenced by both genetic and environmental factors. We propose to study longevity in UK Biobank to better understand genetic and biological markers of lifespan, not focussed on one health condition but on overall mortality. We shall use the unprecedented scale and rich data of Biobank to investigate the degree to which lifespan is inherited, using the latest genomic methods, we shall then search for genetic variants and biomarkers which influence lifespan and estimate how well it is possible to predict lifespan. The proposed research is clearly in the public interest: individuals, health services, and the insurance and pensions industry will benefit from a better understanding of the genetic and environmental influences on lifespan and ageing. There is a clear relationship to health and illness ? mortality being the ultimate end point. We propose to analyse longevity in a number of ways. (a) Assess the degree to which lifespan is genetic, using new methods designed for unrelated people. (b) Search across the genome for regions that are associated with longer or shorter survival. (c) Use the DNA sharing between individuals to try to predict lifespan in UK Biobank and compare to how this works in other populations available to us where individuals area all related and so share more DNA. (d) Assess the contribution of environmental factors and biomarkers such as albumin to lifespan. The research will focus on the ~9,000 individuals who are already deceased and recapture data towards the end of 2015 when complete genotype information is available, but will also use data for all participants.
|Professor James Wilson
|University of Edinburgh
2 related Returns
|Genetic variants linked to education predict longevity
|15 Apr 2020
|Genomics of 1 million parent lifespans implicates novel pathways and common diseases and distinguishes survival chances
|27 Nov 2020