Risk Y-haplotypes and pathogenic variants of Arab-ancestry boys with autism by an exome-wide association study.
Autism is heterogeneous multifactorial neurodevelopmental and neuropsychiatric disorder with repetitive and limited behaviors as well as communication deficits. Prevalence of autism in males is predominant than females, but their genetic association is unclear. The study was performed to investigate Y-chromosome haplotypes, significant risk variants and susceptibility genes associated with autistic Saudi young males with autism. Exome genotyping microarray analysis was performed in Saudi young boys with autism (cases, n = 47) and without autism and other genetic or neurodevelopmental disorders (control, n = 43) to identify the functional exonic risk variations among 243,345 exonic variations. The most significant single nucleotide polymorphisms (SNPs) of protein coding associated with autism in Saudi young boys were studied for functional enrichment. Y-chromosome haplotyping analysis of 6 SNPs such as rs1865680, rs2032624, rs2032658, rs2032631, rs9786153 and rs13447352 uncovered the most significant protective (ACGACA p = 2.94 × 10-9) among the controls and the high risk Y-haplotype (GAAGTC p = 6.85 × 10-6) among autistic boys. Exome association study revealed 6 susceptible genes, MCC, AUTS2, VSX1, SETBP1, CNTN3, and PCDH11Y that were known for autistic disorder. The significant predisposed genes with functional variants of Y-chromomere are strongly connected with spermatogenic failure (p = 8.02 × 10-8), azoospermia (p = 6.32 × 10-7), partial chromosome Y deletion (p = 7.66 × 10-6), HDMs demethylate histones pathway (p = 3.55 × 10-4) and immune system diseases (p = 4.11 × 10-3). Y-haplotypes and highly significant pathogenic exonic variants in MCC, AUTS2, VSX1, SETBP1, CNTN3 and PCDH11Y genes are more influential genetic factors for developing autism in boys of Arab origin.
['Alsubaie|Laila M|LM|', 'Alsuwat|Hind Saleh|HS|', 'Almandil|Noor B|NB|', 'AlSulaiman|Abdulla|A|', 'AbdulAzeez|Sayed|S|', 'Borgio|J Francis|JF|http://orcid.org/0000-0001-7199-1540']
D018912:Arabs D001321:Autistic Disorder D002648:Child D002675:Child, Preschool D041322:Chromosomes, Human, Y D020022:Genetic Predisposition to Disease D055106:Genome-Wide Association Study D006239:Haplotypes D006801:Humans D008297:Male D010865:Pilot Projects D020641:Polymorphism, Single Nucleotide D012307:Risk Factors D000073359:Whole Exome Sequencing
Boy Y-chromosome Haplotype Polymorphism SNPs Autism spectrum disorder