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A genome-wide association study of aging.

ABSTRACT: Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and 8 SNPs that predicted event-free survival (p < 10(-5)). These SNPs are in or near genes that are highly expressed in the brain (HECW2, HIP1, BIN2, GRIA1), genes involved in neural development and function (KCNQ4, LMO4, GRIA1, NETO1) and autophagy (ATG4C), and genes that are associated with risk of various diseases including cancer and Alzheimer's disease. In addition to considerable overlap between the traits, pathway and network analysis corroborated these findings. These findings indicate that variation in genes involved in neurological processes may be an important factor in regulating aging free of major disease and achieving longevity.

SUBMITTER: Walter S

PROVIDER: S-EPMC3193030 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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A genome-wide association study of aging.

Walter Stefan S Atzmon Gil G Demerath Ellen W EW Garcia Melissa E ME Kaplan Robert C RC Kumari Meena M Lunetta Kathryn L KL Milaneschi Yuri Y Tanaka Toshiko T Tranah Gregory J GJ Völker Uwe U Yu Lei L Arnold Alice A Benjamin Emelia J EJ Biffar Reiner R Buchman Aron S AS Boerwinkle Eric E Couper David D De Jager Philip L PL Evans Denis A DA Harris Tamara B TB Hoffmann Wolfgang W Hofman Albert A Karasik David D Kiel Douglas P DP Kocher Thomas T Kuningas Maris M Launer Lenore J LJ Lohman Kurt K KK Lutsey Pamela L PL Mackenbach Johan J Marciante Kristin K Psaty Bruce M BM Reiman Eric M EM Rotter Jerome I JI Seshadri Sudha S Shardell Michelle D MD Smith Albert V AV van Duijn Cornelia C Walston Jeremy J Zillikens M Carola MC Bandinelli Stefania S Baumeister Sebastian E SE Bennett David A DA Ferrucci Luigi L Gudnason Vilmundur V Kivimaki Mika M Liu Yongmei Y Murabito Joanne M JM Newman Anne B AB Tiemeier Henning H Franceschini Nora N

Neurobiology of aging 20110722 11

Human longevity and healthy aging show moderate heritability (20%-50%). We conducted a meta-analysis of genome-wide association studies from 9 studies from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium for 2 outcomes: (1) all-cause mortality, and (2) survival free of major disease or death. No single nucleotide polymorphism (SNP) was a genome-wide significant predictor of either outcome (p < 5 × 10(-8)). We found 14 independent SNPs that predicted risk of death, and ...[more]

PMID: 21782286

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Project description:BACKGROUND:Bovine respiratory disease complex (BRDC) is one of the most important sources of loss within the beef cattle industry in the USA. Steps have been taken to reduce the incidence of BRDC through vaccination. Despite the effectiveness of vaccines, large proportions of cattle still experience morbidity and mortality. Identification of genomic regions that are associated with variation in response to vaccination would allow for the selection of individuals genetically predisposed to respond to vaccination based on specific markers, while heritability and accuracy estimates would help facilitate genomic selection. This in turn may lead to selection for beef cattle herds that may have lower incidence rate of BRDC after vaccination. This study utilizes an Angus herd of more than 2000 head of cattle to identify these regions of association. RESULTS:Genome wide association studies were performed for viral neutralization antibody level and response to vaccination traits against four different viruses associated with BRDC: bovine viral diarrhea virus 1 and 2 (BVDV1 and BVDV2), bovine respiratory syncytial virus (BRSV), and bovine herpesvirus (BHV1). A total of six 1-Mb windows were associated with greater than 1% of the genetic variance for the analyzed vaccination response traits. Heritabilities ranged from 0.08 to 0.21 and prediction accuracy ranged from 0.01 to 0.33 across 7 different vaccination traits. CONCLUSIONS:Although six 1-Mb windows were identified as associated with 1% or greater genetic variance for viral neutralization antibody level and response to vaccination traits, few genes around these windows could readily be considered candidates. This indicates the need for further functional genomic annotation, as these regions appear to be gene deserts. Traits ranged from lowly to moderately heritable, which indicated the potential for selection of individuals that are genetically pre-disposed to respond to vaccination. The relatively low amount of genetic variance accounted for by any 1-Mb window indicated that viral neutralization antibody level and response to vaccination traits are polygenic in nature. Selection for these traits is possible, but likely to be slow due to the low heritabilities and absence of markers with high genetic variation associated with them.

Dataset Information

A genome-wide association study of aging.

Publications

A genome-wide association study of aging.

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