Detecting and exploiting etiologic heterogeneity in epidemiologic studies Journal Article


Authors: Begg, C. B.; Zabor, E. C.
Article Title: Detecting and exploiting etiologic heterogeneity in epidemiologic studies
Abstract: Contemporary searches for new risk factors frequently involve genome-wide explorations of very large numbers of candidate risk variants. Given that diseases can often be classified into subtypes that possess evidence of etiologic heterogeneity, the question arises as to whether or not a search for new risk factors would be improved by looking separately within subtypes. Etiologic risk heterogeneity inevitably increases the signal in at least one of the subtypes, but this advantage may be offset by smaller sample sizes and the increased chances of false discovery. In this article, the authors show that only a relatively modest degree of etiologic heterogeneity is necessary for the subtyping strategies to have improved statistical power. In practice, effective exploitation of etiologic heterogeneity requires strong evidence that the subtypes selected are likely to exhibit substantial heterogeneity. Further, defining the subtypes that demonstrate the most heterogeneous profiles is important for optimizing the search for new risk factors. The concepts are illustrated by using data from a breast cancer study in which results are available separately for estrogen receptor-positive (ER+) and -negative (ER-) tumors.
Keywords: single nucleotide polymorphism; case control study; genetics; case-control studies; polymorphism, single nucleotide; metabolism; classification; tumor markers, biological; genetic association; genome-wide association study; odds ratio; risk factors; breast neoplasms; tumor marker; risk factor; risk; statistical analysis; data interpretation, statistical; breast tumor; receptors, estrogen; estrogen receptor; epidemiology; causality; epidemiologic research design
Journal Title: American Journal of Epidemiology
Volume: 176
Issue: 6
ISSN: 0002-9262
Publisher: Oxford University Press  
Date Published: 2012-09-15
Start Page: 512
End Page: 518
Language: English
PUBMED: 22922440
PROVIDER: scopus
PMCID: PMC3530356
DOI: 10.1093/aje/kws128
DOI/URL:
Notes: --- - "Export Date: 1 February 2013" - "Source: Scopus"
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MSK Authors
  1. Colin B Begg
    241 Begg
  2. Emily Craig Zabor
    136 Zabor