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

doi:10.1007/s10803-014-2197-4

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

Biology

Research output: Contribution to journal › Article › peer-review

75 Scopus citations

Abstract

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 language	English
Pages (from-to)	100-110
Number of pages	11
Journal	Journal of Autism and Developmental Disorders
Volume	45
Issue number	1
DOIs	https://doi.org/10.1007/s10803-014-2197-4
State	Published - Jan 2014

Bibliographical note

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

Funding

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).

Funders	Funder number
NIH National Institute of Child Health and Human Development National Center for Medical Rehabilitation Research	1R01HD059253
National Institute of Mental Health	1R21MH082258-01A2
Vanderbilt Institute for Clinical and Translational Research	RR024975
National Heart, Lung, and Blood Institute (NHLBI)	T32HL007713

Keywords

Biomarkers
Comorbidities
Endophenotypes
Genetic analyses
Phenotypic subgroups
Phenotyping

ASJC Scopus subject areas

Developmental and Educational Psychology

Access to Document

10.1007/s10803-014-2197-4

Cite this

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

abstract = "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.",

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AU - Allen, Melissa J.

AU - Leu, Roberta M.

AU - Johnson, Carl Hirschie

AU - Elsea, Sarah H.

AU - Malow, Beth A.

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AB - 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.

KW - Biomarkers

KW - Comorbidities

KW - Endophenotypes

KW - Genetic analyses

KW - Phenotypic subgroups

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

Access to Document

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