1. Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan.
- Author
-
Sakaue S, Kanai M, Karjalainen J, Akiyama M, Kurki M, Matoba N, Takahashi A, Hirata M, Kubo M, Matsuda K, Murakami Y, Daly MJ, Kamatani Y, and Okada Y
- Subjects
- Adult, Age Factors, Aged, Diabetes Mellitus, Type 2 genetics, Diabetes Mellitus, Type 2 mortality, Female, Finland epidemiology, Genetic Predisposition to Disease epidemiology, Genome-Wide Association Study statistics & numerical data, Humans, Hypertension genetics, Hypertension mortality, Japan epidemiology, Male, Middle Aged, Obesity genetics, Obesity mortality, Polymorphism, Single Nucleotide, Risk Factors, United Kingdom epidemiology, Biological Specimen Banks statistics & numerical data, Genetic Markers genetics, Genome-Wide Association Study methods, Longevity genetics, Multifactorial Inheritance genetics
- Abstract
While polygenic risk scores (PRSs) are poised to be translated into clinical practice through prediction of inborn health risks
1 , a strategy to utilize genetics to prioritize modifiable risk factors driving heath outcome is warranted2 . To this end, we investigated the association of the genetic susceptibility to complex traits with human lifespan in collaboration with three worldwide biobanks (ntotal = 675,898; BioBank Japan (n = 179,066), UK Biobank (n = 361,194) and FinnGen (n = 135,638)). In contrast to observational studies, in which discerning the cause-and-effect can be difficult, PRSs could help to identify the driver biomarkers affecting human lifespan. A high systolic blood pressure PRS was trans-ethnically associated with a shorter lifespan (hazard ratio = 1.03[1.02-1.04], Pmeta = 3.9 × 10-13 ) and parental lifespan (hazard ratio = 1.06[1.06-1.07], P = 2.0 × 10-86 ). The obesity PRS showed distinct effects on lifespan in Japanese and European individuals (Pheterogeneity = 9.5 × 10-8 for BMI). The causal effect of blood pressure and obesity on lifespan was further supported by Mendelian randomization studies. Beyond genotype-phenotype associations, our trans-biobank study offers a new value of PRSs in prioritization of risk factors that could be potential targets of medical treatment to improve population health.- Published
- 2020
- Full Text
- View/download PDF