Genetics of aging, health, and survival: dynamic regulation of human longevity related traits.

Yashin, Anatoliy I

Wu, Deqing

Arbeeva, Liubov S

Arbeev, Konstantin G

Kulminski, Alexander M

Akushevich, Igor

Kovtun, Mikhail

Culminskaya, Irina

Stallard, Eric

Li, Miaozhu

Ukraintseva, Svetlana V

Switzerland

2017-06-05T19:46:16Z

2017-06-05T19:46:16Z

2015

BACKGROUND: The roles of genetic factors in human longevity would be better understood if one can use more efficient methods in genetic analyses and investigate pleiotropic effects of genetic variants on aging and health related traits. DATA AND METHODS: We used EMMAX software with modified correction for population stratification to perform genome wide association studies (GWAS) of female lifespan from the original FHS cohort. The male data from the original FHS cohort and male and female data combined from the offspring FHS cohort were used to confirm findings. We evaluated pleiotropic effects of selected genetic variants as well as gene-smoking interactions on health and aging related traits. Then we reviewed current knowledge on functional properties of genes related to detected variants. RESULTS: The eight SNPs with genome-wide significant variants were negatively associated with lifespan in both males and females. After additional QC, two of these variants were selected for further analyses of their associations with major diseases (cancer and CHD) and physiological aging changes. Gene-smoking interactions contributed to these effects. Genes closest to detected variants appear to be involved in similar biological processes and health disorders, as those found in other studies of aging and longevity e.g., in cancer and neurodegeneration. CONCLUSIONS: The impact of genes on longevity may involve trade-off-like effects on different health traits. Genes that influence lifespan represent various molecular functions but may be involved in similar biological processes and health disorders, which could contribute to genetic heterogeneity of longevity and the lack of replication in genetic association studies.

https://www.ncbi.nlm.nih.gov/pubmed/25918517

https://hdl.handle.net/10161/14821

eng

Frontiers Media SA

Front Genet

10.3389/fgene.2015.00122

CVD

aging changes

gene-environment interaction

genetics of cancer

genetics of longevity

longitudinal data

smoking and life span

Genetics of aging, health, and survival: dynamic regulation of human longevity related traits.

Journal article

Arbeev, Konstantin G|0000-0002-4195-7832

https://www.ncbi.nlm.nih.gov/pubmed/25918517

122

Center for Population Health & Aging

Duke

Duke Cancer Institute

Duke Population Research Center

Duke Population Research Institute

Institutes and Centers

Institutes and Provost's Academic Units

Physics

Sanford School of Public Policy

School of Medicine

Social Science Research Institute

Staff

Trinity College of Arts & Sciences

University Institutes and Centers

Published online

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