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Review: a meta-analysis of GWAS and age-associated diseases.

Publication ,  Journal Article
Jeck, WR; Siebold, AP; Sharpless, NE
Published in: Aging Cell
October 2012

Genome-Wide Association studies (GWAS) offer an unbiased means to understand the genetic basis of traits by identifying single nucleotide polymorphisms (SNPs) linked to causal variants of complex phenotypes. GWAS have identified a host of susceptibility SNPs associated with many important human diseases, including diseases associated with aging. In an effort to understand the genetics of broad resistance to age-associated diseases (i.e., 'wellness'), we performed a meta-analysis of human GWAS. Toward that end, we compiled 372 GWAS that identified 1775 susceptibility SNPs to 105 unique diseases and used these SNPs to create a genomic landscape of disease susceptibility. This map was constructed by partitioning the genome into 200 kb 'bins' and mapping the 1775 susceptibility SNPs to bins based on their genomic location. Investigation of these data revealed significant heterogeneity of disease association within the genome, with 92% of bins devoid of disease-associated SNPs. In contrast, 10 bins (0.06%) were significantly (P < 0.05) enriched for susceptibility to multiple diseases, 5 of which formed two highly significant peaks of disease association (P < .0001). These peaks mapped to the Major Histocompatibility (MHC) locus on 6p21 and the INK4/ARF (CDKN2a/b) tumor suppressor locus on 9p21.3. Provocatively, all 10 significantly enriched bins contained genes linked to either inflammation or cellular senescence pathways, and SNPs near regulators of senescence were particularly associated with disease of aging (e.g., cancer, atherosclerosis, type 2 diabetes, glaucoma). This analysis suggests that germline genetic heterogeneity in the regulation of immunity and cellular senescence influences the human healthspan.

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Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

October 2012

Volume

11

Issue

5

Start / End Page

727 / 731

Location

England

Related Subject Headings

  • Humans
  • Genome-Wide Association Study
  • Developmental Biology
  • Chronic Disease
  • Aging
  • Aged, 80 and over
  • Aged
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences
 

Citation

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Chicago
ICMJE
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Jeck, W. R., Siebold, A. P., & Sharpless, N. E. (2012). Review: a meta-analysis of GWAS and age-associated diseases. Aging Cell, 11(5), 727–731. https://doi.org/10.1111/j.1474-9726.2012.00871.x
Jeck, William R., Alex P. Siebold, and Norman E. Sharpless. “Review: a meta-analysis of GWAS and age-associated diseases.Aging Cell 11, no. 5 (October 2012): 727–31. https://doi.org/10.1111/j.1474-9726.2012.00871.x.
Jeck WR, Siebold AP, Sharpless NE. Review: a meta-analysis of GWAS and age-associated diseases. Aging Cell. 2012 Oct;11(5):727–31.
Jeck, William R., et al. “Review: a meta-analysis of GWAS and age-associated diseases.Aging Cell, vol. 11, no. 5, Oct. 2012, pp. 727–31. Pubmed, doi:10.1111/j.1474-9726.2012.00871.x.
Jeck WR, Siebold AP, Sharpless NE. Review: a meta-analysis of GWAS and age-associated diseases. Aging Cell. 2012 Oct;11(5):727–731.
Journal cover image

Published In

Aging Cell

DOI

EISSN

1474-9726

Publication Date

October 2012

Volume

11

Issue

5

Start / End Page

727 / 731

Location

England

Related Subject Headings

  • Humans
  • Genome-Wide Association Study
  • Developmental Biology
  • Chronic Disease
  • Aging
  • Aged, 80 and over
  • Aged
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
  • 11 Medical and Health Sciences