Biomarkers for aging identified in cross-sectional studies tend to be non-causative

Paul G. Nelson, Daniel E.L. Promislow, Joanna Masel

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Biomarkers are important tools for diagnosis, prognosis, and identification of the causal factors of physiological conditions. Biomarkers are typically identified by correlating biological measurements with the status of a condition in a sample of subjects. Cross-sectional studies sample subjects at a single timepoint, whereas longitudinal studies follow a cohort through time. Identifying biomarkers of aging is subject to unique challenges. Individuals who age faster have intrinsically higher mortality rates and so are preferentially lost over time, in a phenomenon known as cohort selection. In this article, we use simulations to show that cohort selection biases cross-sectional analysis away from identifying causal loci of aging, to the point where cross-sectional studies are less likely to identify loci that cause aging than if loci had been chosen at random. We go on to show this bias can be corrected by incorporating correlates of mortality identified from longitudinal studies, allowing cross-sectional studies to effectively identify the causal factors of aging.

Original languageEnglish (US)
Pages (from-to)466-472
Number of pages7
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume75
Issue number3
DOIs
StatePublished - Feb 14 2020

Keywords

  • Epigenetics
  • Gerontology
  • Longevity
  • Mortality
  • Senescence

ASJC Scopus subject areas

  • Aging
  • Geriatrics and Gerontology

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