A joint analysis of longevity and age-related disease variants for gene expression association
Authors:
- Seungsoo KimSKSeungsoo Kim
- Zhidong TuZTZhidong Tu
Preprint
Abstract
A large number of genetic variants associated with human longevity have been reported but how they play their functions remains elusive. We performed an integrative analysis on 113 genome-wide significant longevity and 14,529 age-related disease variants in the context of putative gene expression regulation. We found that most of the longevity allele types were different from the genotype of disease alleles when they were localized at the same chromosomal positions. Longevity variants were about eight times more likely to be associated with gene expression than randomly selected variants. The directions of the gene expression association were more likely to be opposite between longevity and disease variants when the association occurred to the same gene. Many longevity variants likely function through down-regulating inflammatory response and up-regulating healthy lipid metabolisms. In conclusion, this work helps to elucidate the potential mechanisms of longevity variants for follow-up studies to discover methods to extend human healthspan.Keywords
This publication has 60 references indexed in Scilit:
- A meta-analysis of genome-wide association studies identifies multiple longevity genesNature Communications, 2019
- Genetic associations with age of menopause in familial longevityMenopause, 2019
- The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019Nucleic Acids Research, 2018
- The genetic component of human longevity: New insights from the analysis of pathway‐based SNP‐SNP interactionsAging Cell, 2018
- GWAS of Longevity in CHARGE Consortium Confirms APOE and FOXO3 CandidacyThe Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2014
- Becoming Centenarians: Disease and Functioning Trajectories of Older U.S. Adults as They Survive to 100The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences, 2014
- Genome-wide association meta-analysis of human longevity identifies a novel locus conferring survival beyond 90 years of ageHuman Molecular Genetics, 2014
- LongevityMap: a database of human genetic variants associated with longevityTrends in Genetics, 2013
- Genome-wide association study (GWAS)-identified disease risk alleles do not compromise human longevityProceedings of the National Academy of Sciences, 2010
- Long-term Risk of Incident Vertebral FracturesJAMA, 2007