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Mother’s Genome or Maternally-Inherited Genes Acting in the Fetus Influence Gestational Age in Familial Preterm BirthPlunkett J.a, e, f · Feitosa M.F.c · Trusgnich M.d · Wangler M.F.a, e · Palomar L.a, e · Kistka Z.A.-F.a, e · DeFranco E.A.b, e · Shen T.T.a, e · Stormo A.E.D.a, e · Puttonen H.g · Hallman M.k · Haataja R.k · Luukkonen A.k · Fellman V.h, l · Peltonen L.i, m, n, o, p · Palotie A.i, j, k, o, p · Daw E.W.c · An P.c · Teramo K.g · Borecki I.c, e, f · Muglia L.J.a, b, e, f
Departments of aPediatrics and bObstetrics and Gynecology, Divisions of cStatistical Genomics and dBiostatistics, eCenter for Preterm Birth Research, and fHuman and Statistical Genetics Program, Washington University School of Medicine, St. Louis, Miss., USA; Departments of gObstetrics and Gynecology and hPediatrics, iBiomedicum Helsinki Research Program in Molecular Medicine, jThe Finnish Genome Center, University of Helsinki, Helsinki, kDepartment of Pediatrics, University of Oulu, Oulu, Finland; lDepartment of Pediatrics, Lund University, Lund, Sweden; mDepartment of Clinical Chemistry, Helsinki University Central Hospital, and nDepartment of Molecular Medicine, National Public Health Institute, Helsinki, Finland; oThe Broad Institute of MIT and Harvard, Cambridge, Mass., USA, and pWellcome Trust Sanger Institute, Cambridge, UK Corresponding Author
Louis J. Muglia, MD, PhD
Vanderbilt University Medical Center
2215 Garland Avenue
Nashville, TN 37232-0007 (USA)
Tel. +1 615 322 5893, Fax +1 615 936 6852, E-Mail Louis.Muglia@Vanderbilt.Edu
Objective: While multiple lines of evidence suggest the importance of genetic contributors to risk of preterm birth, the nature of the genetic component has not been identified. We perform segregation analyses to identify the best fitting genetic model for gestational age, a quantitative proxy for preterm birth. Methods: Because either mother or infant can be considered the proband from a preterm delivery and there is evidence to suggest that genetic factors in either one or both may influence the trait, we performed segregation analysis for gestational age either attributed to the infant (infant’s gestational age), or the mother (by averaging the gestational ages at which her children were delivered), using 96 multiplex preterm families. Results: These data lend further support to a genetic component contributing to birth timing since sporadic (i.e. no familial resemblance) and nontransmission (i.e. environmental factors alone contribute to gestational age) models are strongly rejected. Analyses of gestational age attributed to the infant support a model in which mother’s genome and/or maternally-inherited genes acting in the fetus are largely responsible for birth timing, with a smaller contribution from the paternally-inherited alleles in the fetal genome. Conclusion: Our findings suggest that genetic influences on birth timing are important and likely complex.
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