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Sibling Comparisons to Account for Confounding - Reply
Letter/Communication   Peer reviewed

Sibling Comparisons to Account for Confounding - Reply

Viktor H. Ahlqvist, Brian K. Lee and Yu-Han Chiu
JAMA : the journal of the American Medical Association, 42054049
29 Apr 2026
PMID: 42054049

Abstract

General & Internal Medicine Life Sciences & Biomedicine Medicine, General & Internal Science & Technology
In Reply We thank Dr Hswen for her thoughtful engagement with our recent JAMA Guide to Statistics and Methods on sibling comparisons in observational studies.1 In that guide, we outlined the principles underlying this design, along with its key assumptions and potential threats to validity. Sibling comparisons leverage the fact that family members often share genetic and environmental factors that may confound associations in conventional observational analyses. By comparing exposed and unexposed siblings within families, the design can address confounding due to shared, often unmeasured, confounders. However, as with any other observational method, it rests on strong assumptions.

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