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Sex Differences in Genetic Associations With Longevity.

Yi Zeng1, Chao Nie1, Junxia Min1

  • 1Center for the Study of Aging and Human Development, Medical School of Duke University, Durham, North Carolina (Zeng, H. Chen); Center for Healthy Aging and Development Studies, National School of Development, Raissun Institute for Advanced Studies, Peking University, Beijing, China (Zeng, Bai); BGI Education Center, University of Chinese Academy of Sciences, Shenzhen, China (Nie);BGI-Shenzhen, Shenzhen, China (Nie, Xiaomin Liu, Ye, Z. Chen, Bolund, Hou, Xiao Liu, Xu, H. Yang); The First Affiliated Hospital, Institute of Translational Medicine, School of Medicine, Zhejiang University, Hangzhou, China (Min, E. Xie); Business School of Xiangtan University, Xiangtan, China (H. Chen); Division of Non-Communicable Disease Control and Community Health, Chinese Center for Disease Control and Prevention, Beijing, China (Yin); National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing, China (Lv, Shi); Department of Sociology, Peking University, Beijing, China (Lu, Li); School of Life Sciences, Fudan University, Shanghai, China (Ni); Department of Biomedicine, Aarhus University, Aarhus, Denmark (Bolund); Duke Population Research Institute, Duke University, Durham, North Carolina (Land, Yashin, O'Rand); The MOH Key Laboratory of Geriatrics, Beijing Hospital, National Center of Gerontology, Beijing, China (Sun, Z. Yang); School of Life Sciences, Peking University, Beijing, China (Tao, Gu); Boston University, Boston, Massachusetts (Gurinovich, Sebastiani, Perls); University of Bologna, Bologna, Italy (Franceschi); Department of Biostatistics and Bioinformatics, Duke University, Durham, North Carolina (J. Xie); French National Institute on Health and Medical Research and Ecole Pratique des Hautes Etudes, University of Montpellier, Montpellier, France (Robine); Max Planck Institute for Biology of Ageing, Cologne, Germany (Deelen); Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, the Netherlands (Slagboom); Molecular Physiology Institute, Medical Center, Duke University, Durham, North Carolina (Hauser); Department of Neurology, Medical Center, Duke University, Durham, North Carolina (Gottschalk, Lutz); University of Southern Denmark, Odense, Denmark (Tan, Christensen); Human Aging Research Institute and School of Life Science, Nanchang University, Jiangxi, China (Tian); James D. Watson Institute of Genome Sciences, Hangzhou, China (H. Yang); Max Planck Institute for Demographic Research, Rostock, Germany (Vaupel).

JAMA Network Open
|October 9, 2018
PubMed
Summary
This summary is machine-generated.

This study reveals significant sex differences in genetic associations with human longevity, identifying specific genetic loci and pathways unique to males and females. These findings highlight the importance of sex-specific genetic factors for healthy aging and personalized healthcare strategies.

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Area of Science:

  • Genetics
  • Gerontology
  • Personalized Medicine

Background:

  • Sex differences in genetic associations with human longevity are largely unknown.
  • Understanding these differences is crucial for developing individualized healthcare strategies for aging populations.

Purpose of the Study:

  • To investigate sex-specific genetic associations with longevity.
  • To identify sex-specific genetic loci and pathways influencing lifespan.

Main Methods:

  • A population-based case-control study utilizing sex-specific genome-wide association study (GWAS) and polygenic risk score (PRS) analyses.
  • Comparison of centenarians (n=564 males, n=1614 females) with younger controls (n=773 males, n=1526 females) from the Chinese Longitudinal Healthy Longevity Study.

Main Results:

  • Identified 11 male-specific and 11 female-specific longevity loci (P < 10^-5), with significant sex-specific replication and interaction effects.
  • Found 11 male-specific (inflammation, immunity) and 34 female-specific (tryptophan metabolism, PGC-1α) pathways associated with longevity.
  • PRS analyses confirmed significant joint associations of sex-specific loci with longevity in one sex but not the other, with significant sex-PRS interaction effects.

Conclusions:

  • Remarkable sex differences in genetic associations with longevity exist but have been overlooked.
  • This research fills a critical gap, providing a basis for investigating sex-specific genetic variants and their environmental interactions for healthy aging.
  • Findings support the development of more effective, targeted individualized healthcare for elderly males and females.