TY - JOUR
T1 - Genetic Variation in Melatonin Pathway Enzymes in Children with Autism Spectrum Disorder and Comorbid Sleep Onset Delay
AU - Veatch, Olivia J.
AU - Pendergast, Julie S.
AU - Allen, Melissa J.
AU - Leu, Roberta M.
AU - Johnson, Carl Hirschie
AU - Elsea, Sarah H.
AU - Malow, Beth A.
N1 - Publisher Copyright:
© 2014, Springer Science+Business Media New York.
PY - 2014/1
Y1 - 2014/1
N2 - 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.
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
KW - Phenotyping
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U2 - 10.1007/s10803-014-2197-4
DO - 10.1007/s10803-014-2197-4
M3 - Article
C2 - 25059483
AN - SCOPUS:84939877132
SN - 0162-3257
VL - 45
SP - 100
EP - 110
JO - Journal of Autism and Developmental Disorders
JF - Journal of Autism and Developmental Disorders
IS - 1
ER -