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Allelic Variation Within the Putative Autism Spectrum Disorder Risk Gene H omeobox A 1 and Cerebellar Maturation in Typically Developing Children and Adolescents
Author(s) -
Raznahan Armin,
Lee Yohan,
Vaituzis Catherine,
Tran Lan,
Mackie Susan,
Tiemeier Henning,
Clasen Liv,
Lalonde Francois,
Greenstein Dede,
Pierson Ron,
Giedd Jay N
Publication year - 2012
Publication title -
autism research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.656
H-Index - 66
eISSN - 1939-3806
pISSN - 1939-3792
DOI - 10.1002/aur.238
Subject(s) - cerebellum , autism spectrum disorder , autism , biology , homeobox , genotype , brain size , neuroscience , allele , neurodevelopmental disorder , magnetic resonance imaging , genetics , psychology , gene , medicine , developmental psychology , gene expression , radiology
Homeobox A1 ( HOXA 1 ) has been proposed as a candidate gene for autism spectrum disorder ( ASD ) as it regulates embryological patterning of hind‐brain structures implicated in autism neurobiology. In line with this notion, a nonsynonymous single nucleotide polymorphism within a highly conserved domain of HOXA 1 — A218G (rs10951154)—has been linked to both ASD risk, and cross‐sectional differences in superior posterior lobar cerebellar anatomy in late adulthood. Despite evidence for early onset and developmentally dynamic cerebellar involvement in ASD , little is known of the relationship between A218G genotype and maturation of the cerebellum over early development. We addressed this issue using 296 longitudinally acquired structural magnetic resonance imaging brain scans from 116 healthy individuals between 5 and 23 years of age. Mixed models were used to compare the relationship between age and semi‐automated measures of cerebellar volume in A ‐homozygotes ( AA ) and carriers of the G allele ( Gcar ). Total cerebellar volume increased between ages of 5 and 23 years in both groups. However, this was accelerated in the Gcar relative to the AA group ( G enotype‐by‐age interaction term, P = 0.03), and driven by genotype‐dependent differences in the rate of bilateral superior posterior lobar volume change with age ( P = 0.002). Resultantly, although superior posterior lobar volume did not differ significantly between genotype groups at age 5 ( P = 0.9), by age 23 it was 12% greater in G car than AA ( P = 0.002). Our results suggest that common genetic variation within this putative ASD risk gene has the capacity to modify the development of cerebellar systems implicated in ASD neurobiology.