American Journal of Epidemiology Advance Access published online on October 23, 2009
American Journal of Epidemiology, doi:10.1093/aje/kwp328
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Original Contribution |
Maternal Effects for Preterm Birth: A Genetic Epidemiologic Study of 630,000 Families
* Correspondence to Dr. Anna C. Svensson, Division of Public Health Epidemiology, Department of Public Health Sciences, Karolinska Institutet, Norrbacka, Fifth Floor, SE-171 76 Stockholm, Sweden (e-mail: anna.svensson{at}ki.se).
Received for publication September 4, 2008. Accepted for publication June 15, 2009.
This study was undertaken to disentangle the maternal genetic from the fetal genetic effects for preterm birth and to study the possibility of these effects being explained by known risk factors. By cross-linking of the population-based Swedish Multigeneration and Medical Birth registers, 989,027 births between 1992 and 2004 were identified. Alternating logistic regression was applied to model the familial clustering with pairwise odds ratios (PORs), and covariates were included to evaluate if the familial aggregation was explained by exposure to shared risk factors. Generalized linear mixed models were used to estimate the contribution of genetic and environmental effects. Sisters of women who had a preterm delivery had themselves an increased odds of having a preterm delivery (POR = 1.8, 95% confidence interval: 1.5, 2.1), while there was no corresponding increase in odds in families joined by brothers (POR = 1.1, 95% confidence interval: 0.9, 1.4). Twenty-five percent of the variation in preterm birth was explained by maternal genetic factors, whereas fetal genetic factors only marginally influenced the variation in liability. The increased odds ratio between offspring of sisters was independent of maternal risk factors for preterm birth, suggesting that the relative importance of maternal effects is not explained by these well-known risk factors.
components of variance; family; logistic regression; mixed linear model; premature birth; risk factors
Abbreviations: CI, confidence interval; POR, pairwise odds ratio
Editor's note: Related articles appear on pages 000 and 000, an invited commentary on the 3 articles is published on page 000, and a response by Svensson et al. to the commentary is on page 000. In accordance with Journal policy, the authors of the first and third articles were asked whether they wanted to respond to the commentary but chose not to do so.
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