Developmental effects of maternal smoking during pregnancy on the human frontal cortex transcriptome

Stephen A. Semick, Leonardo Collado-Torres, Christina A. Markunas, Joo Heon Shin, Amy Deep-Soboslay, Ran Tao, Laura J. Bierut, Brion S. Maher, Eric O. Johnson, Thomas M. Hyde, Daniel R. Weinberger, Dana B. Hancock, Joel E. Kleinman, Andrew E. Jaffe

Research output: Contribution to journalArticlepeer-review

Abstract

Cigarette smoking during pregnancy is a major public health concern. While there are well-described consequences in early child development, there is very little known about the effects of maternal smoking on human cortical biology during prenatal life. We therefore performed a genome-wide differential gene expression analysis using RNA sequencing (RNA-seq) on prenatal (N=33; 16 smoking-exposed) as well as adult (N=207; 57 active smokers) human post-mortem prefrontal cortices. Smoking exposure during the prenatal period was directly associated with differential expression of 14 genes; in contrast, during adulthood, despite a much larger sample size, only 2 genes showed significant differential expression (FDR<10%). Moreover, 1,315 genes showed significantly different exposure effects between maternal smoking during pregnancy and direct exposure in adulthood (FDR<10%) – these differences were largely driven by prenatal differences that were enriched for pathways previously implicated in addiction and synaptic function. Furthermore, prenatal and age-dependent differentially expressed genes were enriched for genes implicated in non-syndromic autism spectrum disorder (ASD) and were differentially expressed as a set between patients with ASD and controls in post-mortem cortical regions. These results underscore the enhanced sensitivity to the biological effect of smoking exposure in the developing brain and offer novel insight into the effects of maternal smoking during pregnancy on the prenatal human brain. They also begin to address the relationship between in utero exposure to smoking and the heightened risks for the subsequent development of neuropsychiatric disorders. One Sentence Summary Maternal smoking during pregnancy alters the expression of genes within the developing human cortex and these changes are enriched for genes implicated in neuropsychiatric disorders.

Original languageEnglish (US)
JournalUnknown Journal
DOIs
StatePublished - Dec 20 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

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