title: Investigation of the 5q33.3 longevity locus and age-related phenotypes.
abstract: A large meta-analysis recently found the 5q33.3 locus to be associated with survival to ≥ 90 years and lower all-cause mortality, thus suggesting it as a third human longevity locus alongsideAPOEandFOXO3A. The 5q33.3 locus has previously been associated with blood pressure regulation and cardiovascular diseases in middle-aged individuals. However, part of the influence on mortality appears to be independent of cardiovascular phenotypes, and the role of the 5q33.3 locus in longevity and survival is therefore still partly unknown. We investigated the association between the longevity-associated variant rs2149954 on chromosome 5q33.3 and age-related phenotypes in two cohorts of 1,588 and 1,271 long-lived individuals (mean ages 93.1 and 95.9 years, respectively) as well as in 700 middle-aged and 677 elderly individuals (mean ages 52.5 and 78.7 years). Altogether, nominally significant associations between the rs2149954 minor allele and a decreased risk of heart attack and heart failure as well as increased physical functioning were found in the long-lived individuals. In the middle-aged and elderly individuals, rs2149954 minor allele carriers had a lower risk of hypertension. Our results thereby confirm a role of the 5q33.3 locus in cardiovascular health and, interestingly, they also suggest a role in physical functioning.
authors.affiliation: The Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, 5000 Odense C, Denmark.|Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark.
authors.forename: Marianne
authors.initials: M
authors.lastname: Nygaard
authors.affiliation: The Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, 5000 Odense C, Denmark.|Max Planck Odense Center on the Biodemography on Aging, 5000 Odense C, Denmark.
authors.forename: Mikael
authors.initials: M
authors.lastname: Thinggaard
authors.affiliation: The Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, 5000 Odense C, Denmark.|Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark.|Max Planck Odense Center on the Biodemography on Aging, 5000 Odense C, Denmark.|Department of Clinical Biochemistry and Pharmacology, Odense University Hospital, 5000 Odense C, Denmark.
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.affiliation: The Danish Aging Research Center, Epidemiology, Biostatistics and Biodemography, Department of Public Health, University of Southern Denmark, 5000 Odense C, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Christiansen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002895:Chromosomes, Human, Pair 5; D005260:Female; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide
keywords: 5q33.3; age-related phenotypes; genetics; human longevity