Age of onset and effect size in genome-wide association studies

Authors

  • A.J. Agopian,

    1. Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas
    Search for more papers by this author
  • Lisa M. Eastcott,

    1. Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas
    Search for more papers by this author
  • Laura E. Mitchell

    Corresponding author
    1. Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, Texas
    • University of Texas School of Public Health, 1200 Herman Pressler, Houston, TX 77030
    Search for more papers by this author

Abstract

BACKGROUND

Genome-wide association studies (GWAS) have identified many susceptibility loci for complex traits, but have not identified the majority of the genetic contribution to common diseases. We explored whether the magnitude of associations detected in GWAS and, therefore, the likelihood of detecting a significant association for a given sample size, is generally greater for childhood-onset traits (e.g., birth defects) than for traits with onset in adulthood.

METHODS

Data were obtained from the National Human Genome Research Institute Catalog of Published GWAS. Traits were categorized as having an average age of onset in childhood (<18 years, n = 15 traits), early adulthood (18–54 years, n = 32 traits), or late adulthood (≥55 years, n = 31 traits). The relationship between age of onset category and the magnitude of significant associations detected by GWAS was assessed using logistic regression.

RESULTS

Associations characterized by an odds ratio (OR) ≥ 1.5 were significantly more common for GWAS of childhood traits than for late adulthood-onset traits after adjustment for several covariates (adjusted OR, 2.55; 95% confidence interval, 1.37–4.73). Results in subgroup analyses using more stringent inclusion criteria (based on sample size, effect size, p value threshold for inclusion, and novel variant-trait associations) were similar.

CONCLUSIONS

These findings suggest that, on average, marker-trait associations detected in GWAS for traits with young onset may have a larger magnitude of effect than those for traits with adult onset. Therefore, GWAS for young-onset traits, such as birth defects, may be more likely than those for adult-onset traits to identify major genetic risk factors. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.

Ancillary