TY - JOUR
T1 - Family-based genome-wide association study of autism spectrum disorder in middle eastern families
AU - Al-Sarraj, Yasser
AU - Al-Dous, Eman
AU - Taha, Rowaida Z.
AU - Ahram, Dina
AU - Alshaban, Fouad
AU - Tolfat, Mohammed
AU - El-Shanti, Hatem
AU - Albagha, Omar M.E.
N1 - Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/5
Y1 - 2021/5
N2 - Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by ab-normalities in language and social communication with substantial clinical heterogeneity. Genetic factors play an important role in ASD with heritability estimated between 70% to 80%. Genome-wide association studies (GWAS) have identified multiple loci associated with ASD. However, most studies were performed on European populations and little is known about the genetic architecture of ASD in Middle Eastern populations. Here, we report the first GWAS of ASD in the Middle eastern population of Qatar. We analyzed 171 families with ASD, using linear mixed models adjusting for relatedness and other confounders. Results showed that common single nucleotide polymorphisms (SNP) in seven loci are associated with ASD (p < 1 × 10−5 ). Although the identified loci did not reach genome-wide significance, many of the top associated SNPs are located within or near genes that have been implicated in ASD or related neurodevelopmental disorders. These include GORASP2, GABBR2, ANKS6, THSD4, ERCC6L, ARHGEF6, and HDAC8. Additionally, three of the top associated SNPs were significantly associated with gene expression. We also found evidence of association signals in two previously reported ASD-susceptibility loci (rs10099100 and rs4299400). Our results warrant further functional studies and replication to provide further insights into the genetic architecture of ASD.
AB - Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by ab-normalities in language and social communication with substantial clinical heterogeneity. Genetic factors play an important role in ASD with heritability estimated between 70% to 80%. Genome-wide association studies (GWAS) have identified multiple loci associated with ASD. However, most studies were performed on European populations and little is known about the genetic architecture of ASD in Middle Eastern populations. Here, we report the first GWAS of ASD in the Middle eastern population of Qatar. We analyzed 171 families with ASD, using linear mixed models adjusting for relatedness and other confounders. Results showed that common single nucleotide polymorphisms (SNP) in seven loci are associated with ASD (p < 1 × 10−5 ). Although the identified loci did not reach genome-wide significance, many of the top associated SNPs are located within or near genes that have been implicated in ASD or related neurodevelopmental disorders. These include GORASP2, GABBR2, ANKS6, THSD4, ERCC6L, ARHGEF6, and HDAC8. Additionally, three of the top associated SNPs were significantly associated with gene expression. We also found evidence of association signals in two previously reported ASD-susceptibility loci (rs10099100 and rs4299400). Our results warrant further functional studies and replication to provide further insights into the genetic architecture of ASD.
KW - Autism spectrum disorder
KW - Family
KW - Genetic
KW - Genome-wide association
KW - Neuropsychiatric disorders
UR - http://www.scopus.com/inward/record.url?scp=85107230752&partnerID=8YFLogxK
U2 - 10.3390/genes12050761
DO - 10.3390/genes12050761
M3 - Article
C2 - 34069769
AN - SCOPUS:85107230752
SN - 2073-4425
VL - 12
JO - Genes
JF - Genes
IS - 5
M1 - 761
ER -