title: Association of heat shock proteins with all-cause mortality.
abstract: Experimental mild heat shock is widely known as an intervention that results in extended longevity in various models along the evolutionary lineage. Heat shock proteins (HSPs) are highly upregulated immediately after a heat shock. The elevation in HSP levels was shown to inhibit stress-mediated cell death, and recent experiments indicate a highly versatile role for these proteins as inhibitors of programmed cell death. In this study, we examined common genetic variations in 31 genes encoding all members of the HSP70, small HSP, and heat shock factor (HSF) families for their association with all-cause mortality. Our discovery cohort was the Rotterdam study (RS1) containing 5,974 participants aged 55 years and older (3,174 deaths). We assessed 4,430 single nucleotide polymorphisms (SNPs) using the HumanHap550K Genotyping BeadChip from Illumina. After adjusting for multiple testing by permutation analysis, three SNPs showed evidence for association with all-cause mortality in RS1. These findings were followed in eight independent population-based cohorts, leading to a total of 25,007 participants (8,444 deaths). In the replication phase, only HSF2 (rs1416733) remained significantly associated with all-cause mortality. Rs1416733 is a known cis-eQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.
authors.affiliation: Department of Epidemiology, Erasmus Medical Center, Dr. Molewaterplein 50, PO-Box 2040, 3000, CA, Rotterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Broer
authors.forename: E W
authors.initials: EW
authors.lastname: Demerath
authors.forename: M E
authors.initials: ME
authors.lastname: Garcia
authors.forename: G
authors.initials: G
authors.lastname: Homuth
authors.forename: R C
authors.initials: RC
authors.lastname: Kaplan
authors.forename: K L
authors.initials: KL
authors.lastname: Lunetta
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.forename: G J
authors.initials: GJ
authors.lastname: Tranah
authors.forename: S
authors.initials: S
authors.lastname: Walter
authors.forename: A M
authors.initials: AM
authors.lastname: Arnold
authors.forename: G
authors.initials: G
authors.lastname: Atzmon
authors.forename: T B
authors.initials: TB
authors.lastname: Harris
authors.forename: W
authors.initials: W
authors.lastname: Hoffmann
authors.forename: D
authors.initials: D
authors.lastname: Karasik
authors.forename: D P
authors.initials: DP
authors.lastname: Kiel
authors.forename: T
authors.initials: T
authors.lastname: Kocher
authors.forename: L J
authors.initials: LJ
authors.lastname: Launer
authors.forename: K K
authors.initials: KK
authors.lastname: Lohman
authors.forename: J I
authors.initials: JI
authors.lastname: Rotter
authors.forename: H
authors.initials: H
authors.lastname: Tiemeier
authors.forename: A G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: H
authors.initials: H
authors.lastname: Wallaschofski
authors.forename: S
authors.initials: S
authors.lastname: Bandinelli
authors.forename: M
authors.initials: M
authors.lastname: Dörr
authors.forename: L
authors.initials: L
authors.lastname: Ferrucci
authors.forename: N
authors.initials: N
authors.lastname: Franceschini
authors.forename: V
authors.initials: V
authors.lastname: Gudnason
authors.forename: A
authors.initials: A
authors.lastname: Hofman
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.forename: J M
authors.initials: JM
authors.lastname: Murabito
authors.forename: A B
authors.initials: AB
authors.lastname: Newman
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: B M
authors.initials: BM
authors.lastname: Psaty
authors.forename: A V
authors.initials: AV
authors.lastname: Smith
authors.forename: C M
authors.initials: CM
authors.lastname: van Duijn
mesh_terms: D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D002423:Cause of Death / Q000639:trends; D005544:Forecasting; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008136:Longevity / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012189:Retrospective Studies; D014158:Transcription, Genetic; D014481:United States / Q000453:epidemiology
chemical_list: D006360:Heat-Shock Proteins