Initial evidence that polymorphisms in neurotransmitter-regulating genes contribute to being born small for gestational age

Angharad R Morgan; John M D Thompson; Karen E Waldie; Christine M Cornforth; Darko Turic; Edmund J S Sonuga-Barke; Wen-Jiun Lam; Lynnette R Ferguson; Edwin A Mitchell

doi:10.3233/PGE-2012-018

Initial evidence that polymorphisms in neurotransmitter-regulating genes contribute to being born small for gestational age

J Pediatr Genet. 2012 Jun;1(2):103-13. doi: 10.3233/PGE-2012-018.

Authors

Angharad R Morgan¹, John M D Thompson², Karen E Waldie³, Christine M Cornforth⁴, Darko Turic⁴, Edmund J S Sonuga-Barke⁵, Wen-Jiun Lam¹, Lynnette R Ferguson¹, Edwin A Mitchell²

Affiliations

¹ Discipline of Nutrition, FMHS, University of Auckland, Auckland, New Zealand; Nutrigenomics New Zealand, New Zealand.
² Department of Pediatrics, FMHS, University of Auckland, Auckland, New Zealand.
³ Department of Psychology, University of Auckland, Auckland, New Zealand.
⁴ Institute for Disorders of Impulsivity and Attention, School of Psychology, University of Southampton, Southampton, UK.
⁵ Institute for Disorders of Impulsivity and Attention, School of Psychology, University of Southampton, Southampton, UK; Department of Experimental Clinical and Health Psychology, Ghent University, Ghent, Belgium.

Abstract

Being born small for gestational age (SGA) is a putative risk factor for the development of later cognitive and psychiatric health problems. While the inter-uterine environment has been shown to play an important role in predicting birth weight, little is known about the genetic factors that might be important. Here we test the hypothesis that neurotransmitter-regulating genes implicated in psychiatric disorders previously shown to be associated with SGA (such as attention-deficit hyperactivity disorder) are themselves predictive of SGA. DNA was collected from 227 SGA and 319 appropriate for gestational age children taking part in the Auckland Birthweight Collaborative Study. Candidate single nucleotide polymorphisms in genes regulating activity within dopamine, serotonin, glutamate and gamma-aminobutyric acid pathways were genotyped. Multiple regression analysis, controlling for potentially confounding factors, supported nominally significant associations between SGA and single nucleotide polymorphisms in COMT, HTR2A, SLC1A1 and SLC6A1. This is the first evidence that genes implicated in psychiatric disorders previously linked to SGA status themselves predict SGA. This highlights the possibility that the link between SGA and psychiatric disorders such as attention-deficit hyperactivity disorder may in part be genetically determined - that SGA marks pre-existing genetic risk for later problems.

Keywords: ADHD; SGA; SNP; genetic association.