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NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes.

Publication ,  Journal Article
Wojczynski, MK; Jiuan Lin, S; Sebastiani, P; Perls, TT; Lee, J; Kulminski, A; Newman, A; Zmuda, JM; Christensen, K; Province, MA
Published in: The journals of gerontology. Series A, Biological sciences and medical sciences
April 2022

The NIA Long Life Family Study (LLFS) is a longitudinal, multicenter, multinational, population-based multigenerational family study of the genetic and nongenetic determinants of exceptional longevity and healthy aging. The Visit 1 in-person evaluation (2006-2009) recruited 4 953 individuals from 539 two-generation families, selected from the upper 1% tail of the Family Longevity Selection Score (FLoSS, which quantifies the degree of familial clustering of longevity). Demographic, anthropometric, cognitive, activities of daily living, ankle-brachial index, blood pressure, physical performance, and pulmonary function, along with serum, plasma, lymphocytes, red cells, and DNA, were collected. A Genome Wide Association Scan (GWAS) (Ilumina Omni 2.5M chip) followed by imputation was conducted. Visit 2 (2014-2017) repeated all Visit 1 protocols and added carotid ultrasonography of atherosclerotic plaque and wall thickness, additional cognitive testing, and perceived fatigability. On average, LLFS families show healthier aging profiles than reference populations, such as the Framingham Heart Study, at all age/sex groups, for many critical healthy aging phenotypes. However, participants are not uniformly protected. There is considerable heterogeneity among the pedigrees, with some showing exceptional cognition, others showing exceptional grip strength, others exceptional pulmonary function, etc. with little overlap in these families. There is strong heritability for key healthy aging phenotypes, both cross-sectionally and longitudinally, suggesting that at least some of this protection may be genetic. Little of the variance in these heritable phenotypes is explained by the common genome (GWAS + Imputation), which may indicate that rare protective variants for specific phenotypes may be running in selected families.

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Published In

The journals of gerontology. Series A, Biological sciences and medical sciences

DOI

EISSN

1758-535X

ISSN

1079-5006

Publication Date

April 2022

Volume

77

Issue

4

Start / End Page

717 / 727

Related Subject Headings

  • Phenotype
  • Longevity
  • Humans
  • Gerontology
  • Genome-Wide Association Study
  • Cross-Sectional Studies
  • Activities of Daily Living
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 1103 Clinical Sciences
 

Citation

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Wojczynski, M. K., Jiuan Lin, S., Sebastiani, P., Perls, T. T., Lee, J., Kulminski, A., … Province, M. A. (2022). NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 77(4), 717–727. https://doi.org/10.1093/gerona/glab333
Wojczynski, Mary K., Shiow Jiuan Lin, Paola Sebastiani, Thomas T. Perls, Joseph Lee, Alexander Kulminski, Anne Newman, Joe M. Zmuda, Kaare Christensen, and Michael A. Province. “NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes.The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences 77, no. 4 (April 2022): 717–27. https://doi.org/10.1093/gerona/glab333.
Wojczynski MK, Jiuan Lin S, Sebastiani P, Perls TT, Lee J, Kulminski A, et al. NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes. The journals of gerontology Series A, Biological sciences and medical sciences. 2022 Apr;77(4):717–27.
Wojczynski, Mary K., et al. “NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes.The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 77, no. 4, Apr. 2022, pp. 717–27. Epmc, doi:10.1093/gerona/glab333.
Wojczynski MK, Jiuan Lin S, Sebastiani P, Perls TT, Lee J, Kulminski A, Newman A, Zmuda JM, Christensen K, Province MA. NIA Long Life Family Study: Objectives, Design, and Heritability of Cross-Sectional and Longitudinal Phenotypes. The journals of gerontology Series A, Biological sciences and medical sciences. 2022 Apr;77(4):717–727.
Journal cover image

Published In

The journals of gerontology. Series A, Biological sciences and medical sciences

DOI

EISSN

1758-535X

ISSN

1079-5006

Publication Date

April 2022

Volume

77

Issue

4

Start / End Page

717 / 727

Related Subject Headings

  • Phenotype
  • Longevity
  • Humans
  • Gerontology
  • Genome-Wide Association Study
  • Cross-Sectional Studies
  • Activities of Daily Living
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 1103 Clinical Sciences