The relationship between 11 different polygenic longevity scores, parental lifespan, and disease diagnosis in the UK Biobank

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Janith Don
  • Andrew J. Schork
  • Gwênlyn Glusman
  • Noa Rappaport
  • Steve R. Cummings
  • David Duggan
  • Anish Raju
  • Kajsa-Lotta Georgii Hellberg
  • Sophia Gunn
  • Stefano Monti
  • Thomas Perls
  • Jodi Lapidus
  • Laura H. Goetz
  • Paola Sebastiani
  • Nicholas J. Schork

Large-scale genome-wide association studies (GWAS) strongly suggest that most traits and diseases have a polygenic component. This observation has motivated the development of disease-specific “polygenic scores (PGS)” that are weighted sums of the effects of disease-associated variants identified from GWAS that correlate with an individual’s likelihood of expressing a specific phenotype. Although most GWAS have been pursued on disease traits, leading to the creation of refined “Polygenic Risk Scores” (PRS) that quantify risk to diseases, many GWAS have also been pursued on extreme human longevity, general fitness, health span, and other health-positive traits. These GWAS have discovered many genetic variants seemingly protective from disease and are often different from disease-associated variants (i.e., they are not just alternative alleles at disease-associated loci) and suggest that many health-positive traits also have a polygenic basis. This observation has led to an interest in “polygenic longevity scores (PLS)” that quantify the “risk” or genetic predisposition of an individual towards health. We derived 11 different PLS from 4 different available GWAS on lifespan and then investigated the properties of these PLS using data from the UK Biobank (UKB). Tests of association between the PLS and population structure, parental lifespan, and several cancerous and non-cancerous diseases, including death from COVID-19, were performed. Based on the results of our analyses, we argue that PLS are made up of variants not only robustly associated with parental lifespan, but that also contribute to the genetic architecture of disease susceptibility, morbidity, and mortality.

OriginalsprogEngelsk
TidsskriftGeroScience
Antal sider17
ISSN2509-2715
DOI
StatusE-pub ahead of print - 2024

Bibliografisk note

Funding Information:
Open access funding provided by SCELC, Statewide California Electronic Library Consortium Aspects of this work were supported by the following grants from the National Institute on Aging (NIA): U19-AG023122 UH3-AG064706, NIA UH2 UH3 AG064704 U19 AG065169-01A1, U24AG078753, and 5R01EY028606-04.

Funding Information:
UK Biobank data were obtained under the project ID 43036. Research reported in this publication was also supported by the National Institute on Aging of the National Institutes of Health under Award Number U19AG023122. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© The Author(s) 2024.

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