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Cited by 161Advanced Causal Inference TechniquesGenetic Associations and EpidemiologyFamily Dynamics and Relationships

Commentary: Advent of sibling designs

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Donovan, S. J., Susser, E.·2011·International Journal of Epidemiology
DOI 10.1093/ije/dyr057PMC PMC3066430
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Abstract

The rapidly increasing use of sibling comparisons is a welcome development in epidemiology. Although sibling designs have been used by epidemiologists since the mid-20th century, contemporary researchers are extending the range of applications, clarifying appropriate methods1 and introducing novel strategies. The proliferation of sibling studies has not been matched, however, by comparable progress towards a conceptual framework that gives coherence to the new array of approaches. We propose that, as a starting point for a conceptual framework, a fundamental distinction be made between designs that assume a ‘stable’ vs ‘dynamic’ family context. Designs that assume a stable family context exploit the fact that siblings share stable aspects of family context as well as half their genome. In ‘sibling discordance’ studies, for example, we compare outcomes among siblings who are discordant for an exposure of interest, and we want the siblings to be as similar as possible in family context and genetic predisposition. Differences between siblings in family context are potential confounders, and, when measured (e.g. birth order), are controlled in the analyses. Influences of family members upon one another are generally disregarded. In contrast, designs that assume a dynamic family context exploit the fact that siblings and other family members influence each other in a variety of ways. In birth-order studies, for example, we compare outcomes among siblings who encounter different family contexts and may play a role in creating these contexts. Influences of family members upon one another, and the resulting changes in family context, are the topic of investigation. We hope to show that this distinction between sibling designs based on stable vs dynamic family context is readily understood, broadly applicable to traditional as well as novel approaches, and useful as a starting point. To this end, we portray a range of recent sibling studies, and consider them within this framework. Our overarching goal is to stimulate others to further elaborate the conceptual underpinnings of sibling designs. Since the sibling discordance study is probably the most widely used sibling design, we use it to characterize designs based on stable family context. The power of this approach resides in its ability to vary one aspect of the environment while keeping so much else similar. Although sibling discordance studies can be traced to the 19th century,2 rigorous use of the design began after World War II. In the 1960s, Record et al.3,4 applied it to control familial confounding in their studies of the relation of birthweight to offspring verbal reasoning scores on school examinations. This remarkable work set an early precedent for subsequent studies5 (as did other work by these authors).6 Sibling discordance studies are particularly suitable for examining the relation of prenatal exposures to offspring outcomes. We use discordance in maternal exposures or conditions across pregnancies to indicate variation in the in utero experience of same-sex siblings. Same-sex siblings share enough stable aspects of family environment and genetic predisposition that the strategy substantially reduces the potential for confounding. This provides a major advantage over population studies of unrelated individuals. The approach also offers a major advantage over the twin design. Twins are, by definition, products of the same pregnancy, and, while their in utero experience can be very different, we resort to proxies such as birth outcomes to gauge this difference. The elegant paper by Obel et al.7 in this issue of the IJE offers an example of a study examining a prenatal exposure that compared results from a full population to results from discordant siblings within that population. It was a registry study of a national cohort in Finland. The authors first found a strong association between maternal smoking during pregnancy and offspring ICD-10 (International Classification of Diseases, 10th Revision) Hyperkinetic Disorder in the full cohort. Next, they identified mothers who smoked during one pregnancy, but not during another, and compared hyperkinetic disorder outcomes in the relevant siblings. This second analysis found only a minimal association. They concluded that the first result was confounded by family factors (genes and/or family context) and that there was little or no causal relationship between prenatal smoking and hyperkinetic disorder. The authors noted, however, that the validity of their conclusion rested upon a crucial assumption that family factors relevant to hyperkinetic disorder were stable and therefore similar across siblings. Notwithstanding this caveat, the most plausible interpretation is that the sibling analysis revealed that the population result was confounded. Numerous other sibling discordance studies8–10 (as well as other approaches11) have also suggested that associations between prenatal smoking and offspring outcome

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  1. Sutcliffe AG, Ludwig M. Outcome of assisted reproduc- tion. Lancet 2007;370:351-59.

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Authors
Donovan, S. J., & Susser, E.
Affiliations
New York State Psychiatric Institute (US)
Corresponding author
Susser, E.
ORCID
Susser, E.
Venue
International Journal of Epidemiology
Publisher
Oxford University Press (OUP)
Published
2011-03-29
Volume
40
Issue
2
Pages
345-349
ISSN
  • 0300-5771 (ISSN-L)
  • 1464-3685
DOI
10.1093/ije/dyr057
PMC
PMC3066430
OpenAlex
W2144367795
Cited by
161
References
30
Citations by year
2026: 3 · 2025: 2 · 2024: 4 · 2023: 12 · 2022: 8 · 2021: 11 · 2020: 6 · 2019: 12 · 2018: 11 · 2017: 16 · 2016: 6 · 2015: 10 · 2014: 19 · 2013: 18 · 2012: 14
Type
journal article
Language
en
Open access
Locations
  • International Journal of Epidemiology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • HighWire Press Open Archive (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging (P01 AG 02302)
Topics
  • Physical Sciences › Mathematics › Statistics and Probability › Advanced Causal Inference Techniques
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Social Sciences › Demography › Family Dynamics and Relationships
Keywords
sibling discordance, birth order, familial confounding, birth weight, prenatal exposure, maternal alcohol consumption, maternal depression, maternal employment
MeSH terms
Epidemiologic Methods, Family, Humans, Research Design, Siblings

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