The mathematical limits of genetic prediction for complex chronic disease

Details

• Personal Author:
  Galea S ; Keyes KM ; Koenen KC ; Smith GD
• Description:
  BACKGROUND: Attempts at predicting individual risk of disease based on common germline genetic variation have largely been disappointing. The present paper formalises why genetic prediction at the individual level is and will continue to have limited utility given the aetiological architecture of most common complex diseases. METHODS: Data were simulated on one million populations with 10 000 individuals in each populations with varying prevalences of a genetic risk factor, an interacting environmental factor and the background rate of disease. The determinant risk ratio and risk difference magnitude for the association between a gene variant and disease is a function of the prevalence of the interacting factors that activate the gene, and the background rate of disease. RESULTS: The risk ratio and total excess cases due to the genetic factor increase as the prevalence of interacting factors increase, and decrease as the background rate of disease increases. Germline genetic variations have high predictive capacity for individual disease only under conditions of high heritability of particular genetic sequences, plausible only under rare variant hypotheses. CONCLUSIONS: Under a model of common germline genetic variants that interact with other genes and/or environmental factors in order to cause disease, the predictive capacity of common genetic variants is determined by the prevalence of the factors that interact with the variant and the background rate. A focus on estimating genetic associations for the purpose of prediction without explicitly grounding such work in an understanding of modifiable (including environmentally influenced) factors will be limited in its ability to yield important insights about the risk of disease. [Description provided by NIOSH]
• Subjects:
  Environmental Exposure Environmental Health Epidemiology Genetics Occupational Health Risk Assessment Risk Factors Safety
• Keywords:
  Author Keywords: Epidemiology Diseases Environmental-exposure Environmental-factors Exposure-levels Gene Environment Interactions Genes Germ-cells Mathematical-models Models Risk-factors

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• ISSN:
  0143-005X
• Document Type:
  Text
• Funding:
  Cooperative Agreement
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; New York ; OSHA Region 1 ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  69
• Issue:
  6
• NIOSHTIC Number:
  nn:20047466
• Citation:
  J Epidemiol Community Health 2015 Jun; 69(6):574-579
• Contact Point Address:
  Dr Katherine M Keyes, Department of Epidemiology, Columbia University, 722 West 168th Street, #503, New York, NY 10032
• Email:
  kmk2104@columbia.edu
• Federal Fiscal Year:
  2015
• Performing Organization:
  Icahn School of Medicine at Mount Sinai, New York
• Peer Reviewed:
  True
• Start Date:
  20120901
• Source Full Name:
  Journal of Epidemiology and Community Health
• End Date:
  20180831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:f3d1397a91ca0822160e57c962575a2b444dcbd2c28e93f09e2dc52e98c8ec149fadb2f570235a6eab0df06750633f00007ecb197fde665a199eef36f5780593
• Download URL:
  https://stacks.cdc.gov/view/cdc/202522/cdc_202522_DS1.pdf
• File Type:
  [PDF - 1.59 MB ]