Toward localizing genes underlying cerebral asymmetry and mental health.
Genome investigations of autism, attention deficit hyperactivity disorder (ADHD), and dyslexia suggest possible genetic overlap. Atypical cerebral asymmetry (ACA), the absence of the left hemisphere dominance for language, may be a shared phenotype due to genes located in regions of overlap. A binomal test is used to evaluate whether linked regions overlap more than expected by chance for 15 genome-wide scans in autism, ADHD, and dyslexia. Significant evidence of linkage overlap (P = 10(-7)) is seen for autism, ADHD, and dyslexia for seven chromosomal regions (2p11-12, 5p13, 7q22-33, 9q33-34, 13q22, 16p13, and 17p11-q11). Linkage analysis of ACA and molecular markers for 270 sibling pairs with ADHD is conducted using the Haseman-Elston statistic. Linkage analysis supports ACA as a shared phenotype with risk genes located on 9q33-34 or 16p13 (P < 0.004). Further support stems from the overlap of these regions in schizophrenia, bipolar illness, specific language impairment (SLI), and handedness, all traits associated with ACA. Autism, ADHD, and dyslexia share regions of linkage overlap and ACA may be a shared phenotype for such genes similar to HLA in autoimmune disease. Because ACA is associated with certain aspects of creativity, such risk genes may also be enhancer genes for creativity.
Smalley
Susan L
SL
Center for Neurobehavioral Genetics, UCLA Neuropsychiatric Institute, David Geffen School of Medicine at UCLA, Los Angeles, California 90024, USA. ssmalley@mednet.ucla.edu
Loo
Sandra K
SK
Yang
May H
MH
Cantor
Rita M
RM
D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D002874:Chromosome Mapping; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D004410:Dyslexia / Q000235:genetics; D007839:Functional Laterality / Q000502:physiology; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D006801:Humans; D008603:Mental Health; D035781:Siblings