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Genetic Associations in Preterm Birth: A Primer of Marker Selection, Study Design, and Data Analysis

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Abstract

Spontaneous preterm birth (PTB; delivery before 37 weeks gestation) is a primary risk factor for infant morbidity and mortality. The etiology is unclear, but there is evidence that there is a genetic predisposition to PTB. Armed with the suggestion of genetic risk factors and the failure to identify useful biomarkers, investigators are starting to actively pursue the role of genetic predisposition in PTB. Several studies have been done to date assessing the role of single gene variants. However, positive findings have failed to replicate. We argue that heterogeneity in study designs, definition of phenotype, single-nucleotide polymorphism (SNP) selection, population selection, and sample size makes data interpretation difficult in complex phenotypes such as PTB. In this review, we introduce general concepts of study designs in genetic epidemiology, selection of candidate genes and markers for analysis, and analytical methodologies. We also introduce how the concept of gene-gene interactions (biologic epistatis) and gene-environment interactions may affect the predisposition to PTB.

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Authors and Affiliations

  1. The Perinatal Research Center, 2300 Patterson St., Nashville, TN, 37203, USA

    Ramkumar Menon MS, Stephen J. Fortunato MD, Poul Thorsen MD, PhD & Scott Williams PhD

  2. North Atlantic Neuro-epidemiology Alliances (NANEA), Institute for Public Health, University of Aarhus, Aarhus, Denmark

    Ramkumar Menon MS, Stephen J. Fortunato MD, Poul Thorsen MD, PhD & Scott Williams PhD

  3. Department of Medicine, Vanderbilt University, Nashville, TN, USA

    Ramkumar Menon MS, Stephen J. Fortunato MD, Poul Thorsen MD, PhD & Scott Williams PhD

  4. Center for Human Genetic Research, Vanderbilt University, Nashville, TN, USA

    Ramkumar Menon MS, Stephen J. Fortunato MD, Poul Thorsen MD, PhD & Scott Williams PhD

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  1. Ramkumar Menon MS
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  2. Stephen J. Fortunato MD
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Correspondence to Ramkumar Menon MS.

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The authors would like to thank Jake McCauley for his cntical reading of the manuscript and his constructive comments. We also thank Thrasher Research Funds, UT.

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Menon, R., Fortunato, S.J., Thorsen, P. et al. Genetic Associations in Preterm Birth: A Primer of Marker Selection, Study Design, and Data Analysis. Reprod. Sci. 13, 531–541 (2006). https://doi.org/10.1016/j.jsgi.2006.09.006

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