Passive rGE or Developmental Gene-Environment Cascade? An Investigation of the Role of Xenobiotic Metabolism Genes in the Association Between Smoke Exposure During Pregnancy and Child Birth Weight

• Type of Material: Article
• Authors: Kristine Marceau, Rhode Island Hospital; Rohan H. Palmer, Emory University; Jenae M. Neiderhiser, Pennsylvania State University; Taylor F. Smith, California Polytechnic State University; John E. McGeary, Rhode Island Hospital; Valerie S. Knopik, Rhode Island Hospital
• Language: English
• Date: 2016-05-01
• Publisher: Springer (part of Springer Nature): Springer Open Choice Hybrid Journals
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016, Springer Science+Business Media New York.
• Final Published Version (URL): http://dx.doi.org/10.1007/s10519-016-9778-2
• Title of Journal or Parent Work: Behavior Genetics
• ISSN: 0001-8244
• Volume: 46
• Issue: 3
• Start Page: 365
• End Page: 377
• Grant/Funding Information: The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2); and the University of Bristol provide core support for ALSPAC.; Authors were supported by the following sources: T32MH019927 and T32DA016184 (Marceau); K01AA021113 (Palmer); MH092118 (Neiderhiser); T32MH19927 (Smith);DA023134 (Knopik).
• Keywords: Regression Analysis; Gene-Environment Interaction; Child; Maternal Exposure; Pregnancy; Birth weight; Smoking; Polygenic; ALSPAC; Humans; Female; Smoking during pregnancy; Passive gene-environment correlation; Xenobiotics; Birth Weight
• Research Categories: Health Sciences, Human Development; Psychology, Behavioral; Biology, Genetics

Abstract

There is considerable evidence that smoke exposure during pregnancy (SDP) environmentally influences birth weight after controlling for genetic influences and maternal characteristics. However, maternal smoking during pregnancy—the behavior that leads to smoke exposure during pregnancy—is also genetically-influenced, indicating the potential role of passive gene-environment correlation. An alternative to passive gene-SDP correlation is a cascading effect whereby maternal and child genetic influences are causally linked to prenatal exposures, which then have an ‘environmental’ effect on the development of the child’s biology and behavior. We describe and demonstrate a conceptual framework for disentangling passive rGE from this cascading GE effect using a systems-based polygenic scoring approach comprised of genes shown to be important in the xenobiotic (substances foreign to the body) metabolism pathway. Data were drawn from 5044 families from the Avon Longitudinal Study of Parents and Children with information on maternal SDP, birth weight, and genetic polymorphisms in the xenobiotic pathway. Within a k-fold cross-validation approach (k = 5), we created weighted maternal and child polygenic scores using 18 polymorphisms from 10 genes that have been implicated in the xenobiotic metabolism pathway. Mothers and children shared variation in xenobiotic metabolism genes. Amongst mothers who smoked during pregnancy, neither maternal nor child xenobiotic metabolism polygenic scores were associated with a higher likelihood of smoke exposure during pregnancy, or the severity of smoke exposure during pregnancy (and therefore, neither proposed mechanism was supported), or with child birth weight. SDP was consistently associated with lower child birth weight controlling for the polygenic scores, maternal educational attainment, social class, psychiatric problems, and age. Limitations of the study design and the potential of the framework using other designs are discussed.