Genetic Variation in Melatonin Pathway Enzymes in Children with Autism Spectrum Disorder and Comorbid Sleep Onset Delay

Olivia J. Veatch, Julie S. Pendergast, Melissa J. Allen, Roberta M. Leu, Carl Hirschie Johnson, Sarah H. Elsea, Beth A. Malow

Research output: Contribution to journalArticlepeer-review

52 Scopus citations


Sleep disruption is common in individuals with autism spectrum disorder (ASD). Genes whose products regulate endogenous melatonin modify sleep patterns and have been implicated in ASD. Genetic factors likely contribute to comorbid expression of sleep disorders in ASD. We studied a clinically unique ASD subgroup, consisting solely of children with comorbid expression of sleep onset delay. We evaluated variation in two melatonin pathway genes, acetylserotonin O-methyltransferase (ASMT) and cytochrome P450 1A2 (CYP1A2). We observed higher frequencies than currently reported (p < 0.04) for variants evidenced to decrease ASMT expression and related to decreased CYP1A2 enzyme activity (p ≤ 0.0007). We detected a relationship between genotypes in ASMT and CYP1A2 (r2 = 0.63). Our results indicate that expression of sleep onset delay relates to melatonin pathway genes.

Original languageEnglish
Pages (from-to)100-110
Number of pages11
JournalJournal of Autism and Developmental Disorders
Issue number1
StatePublished - Jan 2014

Bibliographical note

Funding Information:
Special thanks to the families and individuals who participated in the studies from which this work was made possible. We also gratefully acknowledge Ms. Karen Adkins, CCRC for help with sample collection, and the laboratory of Dr. Jonathan L. Haines for providing access to equipment to accomplish the genotyping and sequencing. Grant support was also provided to Dr. Malow from the National Institute of Child Health and Human Development (1R01HD059253), and Vanderbilt Institute for Clinical and Translational Research (RR024975). Dr. Johnson received grant support from the National Institute of Mental Health (1R21MH082258-01A2).

Publisher Copyright:
© 2014, Springer Science+Business Media New York.


  • Biomarkers
  • Comorbidities
  • Endophenotypes
  • Genetic analyses
  • Phenotypic subgroups
  • Phenotyping

ASJC Scopus subject areas

  • Developmental and Educational Psychology


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