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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Current genomewide association studies account for only a small fraction of the estimated heritabilities of genetically complex neuropsychiatric disorders, indicating they are likely to result from the small effects of numerous predisposing variants, many of which have gone undetected. The statistical power to detect associations of common variants with small effects is increased by conducting joint association tests of a single nucleotide polymorphism (SNP), an additional risk factor (F), and their interaction. F can represent an environmental exposure, another genotype or any source of genetic heterogeneity. In case and control studies, logistic regression makes joint tests straightforward. This analytic method cannot be employed directly when SNP transmission tests are used to detect associations in parent/affected child trios and multiplex families. However, the method can be implemented using the case/pseudocontrol approach. We applied this approach to analyze data from a genomewide association study of multiplex families ascertained for Autism Spectrum Disorder, where sex was used to define the F. Joint analyses revealed two associations exceeding genomewide significance. One novel gene, Ryandine Receptor 2, implicated in calcium channel defects, was identified with a joint P-value of 3.9E-11. Calcium channel defects have been connected to Autism spectrum disorder (ASD) by Timothy Syndrome, which is Mendelian, and a previous targeted sex-specific association analysis of idiopathic Autism. A second gene, uridine phosphorylase 2, with a joint P-value of 2.3E-9, has been previously linked and associated with Autism in independent samples. These findings highlight two Autism candidate genes for follow-up studies.
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PMID:Allowing for sex differences increases power in a GWAS of multiplex Autism families. 2115 Nov 89

Examining sex differences in the brain has been historically contentious but is nonetheless important for advancing mental health for both girls and boys. Unfortunately, females in biomedical research remain underrepresented in most mental health conditions including autism spectrum disorders (ASD), even though equal inclusion of females would improve treatment for girls and yield benefits to boys. This review examines sex differences in the relationship between neuroanatomy and neurogenetics of ASD. Recent findings reveal that girls diagnosed with ASD exhibit more intellectual and behavioral problems compared to their male counterparts, suggesting that girls may be less likely diagnosed in the absence of such problems or that they require a higher mutational load to meet the diagnostic criteria. Thus far, the female biased effect of chromosome 4, 5p15.33, 8p, 9p24.1, 11p12-13, 15q, and Xp22.3 and the male biased effect of 1p31.3, 5q12.3, 7q, 9q33.3, 11q13.4, 13q33.3, 16p11.2, 17q11-21, Xp22.33/Yp11.31, DRD1, NLGN3, MAOA, and SHANK1 deletion have been discovered in ASD. The SNPs of genes such as RYR2, UPP2, and the androgen receptor gene have been shown to have sex-biasing factors in both girls and boys diagnosed with ASD. These sex-related genetic factors may drive sex differences in the neuroanatomy of these girls and boys, including abnormal enlargement in temporal gray and white matter volumes, and atypical reduction in cerebellar gray matter volumes and corpus callosum fibers projecting to the anterior frontal cortex in ASD girls relative to boys. Such factors may also be responsible for the attenuation of brain sexual differentiation in adult men and women with ASD; however, much remains to be uncovered or replicated. Future research should leverage further the association between neuroanatomy and genetics in girls for an integrated and interdisciplinary understanding of ASD.
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PMID:Developmental neurogenetics and multimodal neuroimaging of sex differences in autism. 2678 67