title: The reduction of vascular disease risk mutations contributes to longevity in the Chinese population.
abstract: OBJECTIVE
  Genetic factors play important roles in determining human lifespan. Although some "longevity genes" have been identified to be implicated in human longevity, many disease-associated variants were also observed in the long-lived individuals. The oldest old and their offspring usually have a lower prevalence of age-related diseases, which is likely attributed to a reduction or an absence of disease risk variants.
  
  
  RESULTS
  To test this hypothesis, 23 disease risk single nucleotide polymorphisms (SNPs), identified by previous genome-wide association studies (GWASs), were selected and genotyped in 1074 samples consisting of 574 longevity subjects (over 90 years old) and 500 younger controls. Our results revealed that 5 SNPs (rs2144300, rs1864163, rs2200733, rs1967017, and rs7193343) displayed significantly lower allelic frequencies and odds ratios (ORs) in the longevity group than that in the control group. The frequencies of homozygous mutation genotypes and corresponding ORs of the rs1864163, rs2200733, rs127430, rs1967017, and rs12413409 were lower in the longevity subjects. Interestingly, most of the abovementioned SNPs convey susceptibility to cardiovascular disease (CVD), which is the leading cause of deaths in old adults but shows a much lower incidence in the longevity individuals and their offspring.
  
  
  CONCLUSIONS
  Taking into account the observation that the longevity subjects and their offspring have lower rate of cardiovascular mortality, it is then most plausible that the lack of disease risk variants, especially the CVD, is a genetic contributor to longevity in the Chinese population.
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China ; KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
authors.forename: Yong-Han
authors.initials: YH
authors.lastname: He
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China ; KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Nutrition and Food Hygiene, Public Health College, Harbin Medical University, 157 Baojian Road, Nangang District, Harbin 150081, China.
authors.forename: Ming-Xin
authors.initials: MX
authors.lastname: Bi
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China ; KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
authors.forename: Li-Qin
authors.initials: LQ
authors.lastname: Yang
authors.affiliation: Dujiangyan Longevity Research Centre, Dujiangyan 611830, China.
authors.forename: Liang-You
authors.initials: LY
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming 650223, China ; KIZ/CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming 650223, China.
authors.forename: Qing-Peng
authors.initials: QP
authors.lastname: Kong
keywords: AD, Alzheimer Disease; CHB, Chinese Han Beijing; CVD, cardiovascular disease; Cardiovascular disease; GWAS, genome-wide association study; Heritability; Longevity; MAF, minor allele frequency; OR, odds ratio; PCR, polymerase chain reaction; PD, Parkinson Disease; SNP, single nucleotide polymorphism.; Single nucleotide polymorphism