Association of heat shock proteins with all-cause mortality

L. Broer; E. W. Demerath; M. E. Garcia; G. Homuth; R. C. Kaplan; K. L. Lunetta; T. Tanaka; G. J. Tranah; S. Walter; A. M. Arnold; G. Atzmon; T. B. Harris; W. Hoffmann; D. Karasik; D. P. Kiel; T. Kocher; L. J. Launer; K. K. Lohman; J. I. Rotter; H. Tiemeier; A. G. Uitterlinden; H. Wallaschofski; S. Bandinelli; M. Dörr; L. Ferrucci; N. Franceschini; V. Gudnason; A. Hofman; Y. Liu; J. M. Murabito; A. B. Newman; B. A. Oostra; B. M. Psaty; A. V. Smith; C. M. Van Duijn

doi:10.1007/s11357-012-9417-7

Association of heat shock proteins with all-cause mortality

L. Broer, E. W. Demerath, M. E. Garcia, G. Homuth, R. C. Kaplan, K. L. Lunetta, T. Tanaka, G. J. Tranah, S. Walter, A. M. Arnold, G. Atzmon, T. B. Harris, W. Hoffmann, D. Karasik, D. P. Kiel, T. Kocher, L. J. Launer, K. K. Lohman, J. I. Rotter, H. TiemeierA. G. Uitterlinden, H. Wallaschofski, S. Bandinelli, M. Dörr, L. Ferrucci, N. Franceschini, V. Gudnason, A. Hofman, Y. Liu, J. M. Murabito, A. B. Newman, B. A. Oostra, B. M. Psaty, A. V. Smith, C. M. Van Duijn

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4 Scopus citations

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-causemortality. Rs1416733 is a known ciseQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

Original language	English (US)
Pages (from-to)	1367-1376
Number of pages	10
Journal	Age
Volume	35
Issue number	4
DOIs	https://doi.org/10.1007/s11357-012-9417-7
State	Published - Aug 2013
Externally published	Yes

Keywords

All-cause mortality
Heat shock proteins
Heatshock factor 2

ASJC Scopus subject areas

Aging
Geriatrics and Gerontology
General Medicine

Access to Document

10.1007/s11357-012-9417-7

Cite this

Broer, L., Demerath, E. W., Garcia, M. E., Homuth, G., Kaplan, R. C., Lunetta, K. L., Tanaka, T., Tranah, G. J., Walter, S., Arnold, A. M., Atzmon, G., Harris, T. B., Hoffmann, W., Karasik, D., Kiel, D. P., Kocher, T., Launer, L. J., Lohman, K. K., Rotter, J. I., ... Van Duijn, C. M. (2013). Association of heat shock proteins with all-cause mortality. Age, 35(4), 1367-1376. https://doi.org/10.1007/s11357-012-9417-7

Broer, L, Demerath, EW, Garcia, ME, Homuth, G, Kaplan, RC, Lunetta, KL, Tanaka, T, Tranah, GJ, Walter, S, Arnold, AM, Atzmon, G, Harris, TB, Hoffmann, W, Karasik, D, Kiel, DP, Kocher, T, Launer, LJ, Lohman, KK, Rotter, JI, Tiemeier, H, Uitterlinden, AG, Wallaschofski, H, Bandinelli, S, Dörr, M, Ferrucci, L, Franceschini, N, Gudnason, V, Hofman, A, Liu, Y, Murabito, JM, Newman, AB, Oostra, BA, Psaty, BM, Smith, AV & Van Duijn, CM 2013, 'Association of heat shock proteins with all-cause mortality', Age, vol. 35, no. 4, pp. 1367-1376. https://doi.org/10.1007/s11357-012-9417-7

@article{9e0f390f8b5d449e9ad74e9d3af87e90,

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-causemortality. Rs1416733 is a known ciseQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.",

keywords = "All-cause mortality, Heat shock proteins, Heatshock factor 2",

author = "L. Broer and Demerath, {E. W.} and Garcia, {M. E.} and G. Homuth and Kaplan, {R. C.} and Lunetta, {K. L.} and T. Tanaka and Tranah, {G. J.} and S. Walter and Arnold, {A. M.} and G. Atzmon and Harris, {T. B.} and W. Hoffmann and D. Karasik and Kiel, {D. P.} and T. Kocher and Launer, {L. J.} and Lohman, {K. K.} and Rotter, {J. I.} and H. Tiemeier and Uitterlinden, {A. G.} and H. Wallaschofski and S. Bandinelli and M. D{\"o}rr and L. Ferrucci and N. Franceschini and V. Gudnason and A. Hofman and Y. Liu and Murabito, {J. M.} and Newman, {A. B.} and Oostra, {B. A.} and Psaty, {B. M.} and Smith, {A. V.} and {Van Duijn}, {C. M.}",

year = "2013",

month = aug,

doi = "10.1007/s11357-012-9417-7",

language = "English (US)",

volume = "35",

pages = "1367--1376",

journal = "Age",

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T1 - Association of heat shock proteins with all-cause mortality

AU - Broer, L.

AU - Demerath, E. W.

AU - Garcia, M. E.

AU - Homuth, G.

AU - Kaplan, R. C.

AU - Lunetta, K. L.

AU - Tanaka, T.

AU - Tranah, G. J.

AU - Walter, S.

AU - Arnold, A. M.

AU - Atzmon, G.

AU - Harris, T. B.

AU - Hoffmann, W.

AU - Karasik, D.

AU - Kiel, D. P.

AU - Kocher, T.

AU - Launer, L. J.

AU - Lohman, K. K.

AU - Rotter, J. I.

AU - Tiemeier, H.

AU - Uitterlinden, A. G.

AU - Wallaschofski, H.

AU - Bandinelli, S.

AU - Dörr, M.

AU - Ferrucci, L.

AU - Franceschini, N.

AU - Gudnason, V.

AU - Hofman, A.

AU - Liu, Y.

AU - Murabito, J. M.

AU - Newman, A. B.

AU - Oostra, B. A.

AU - Psaty, B. M.

AU - Smith, A. V.

AU - Van Duijn, C. M.

PY - 2013/8

Y1 - 2013/8

N2 - 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-causemortality. Rs1416733 is a known ciseQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

AB - 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-causemortality. Rs1416733 is a known ciseQTL for HSF2. Our findings suggest a role of HSF2 in all-cause mortality.

KW - All-cause mortality

KW - Heat shock proteins

KW - Heatshock factor 2

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VL - 35

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EP - 1376

JO - Age

JF - Age

IS - 4

ER -

Association of heat shock proteins with all-cause mortality

Abstract

Keywords

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