Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families

<div><p>Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by abnormalities 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 as...

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محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Yasser Al-Sarraj (11721425) (author)
مؤلفون آخرون: Eman Al-Dous (124700) (author), Rowaida Z. Taha (8854754) (author), Dina Ahram (18508161) (author), Fouad Alshaban (6176771) (author), Mohammed Tolfat (18508164) (author), Hatem El-Shanti (492142) (author), Omar M.E. Albagha (18508167) (author)
منشور في: 2021
الموضوعات:
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author Yasser Al-Sarraj (11721425)
author2 Eman Al-Dous (124700)
Rowaida Z. Taha (8854754)
Dina Ahram (18508161)
Fouad Alshaban (6176771)
Mohammed Tolfat (18508164)
Hatem El-Shanti (492142)
Omar M.E. Albagha (18508167)
author2_role author
author
author
author
author
author
author
author_facet Yasser Al-Sarraj (11721425)
Eman Al-Dous (124700)
Rowaida Z. Taha (8854754)
Dina Ahram (18508161)
Fouad Alshaban (6176771)
Mohammed Tolfat (18508164)
Hatem El-Shanti (492142)
Omar M.E. Albagha (18508167)
author_role author
dc.creator.none.fl_str_mv Yasser Al-Sarraj (11721425)
Eman Al-Dous (124700)
Rowaida Z. Taha (8854754)
Dina Ahram (18508161)
Fouad Alshaban (6176771)
Mohammed Tolfat (18508164)
Hatem El-Shanti (492142)
Omar M.E. Albagha (18508167)
dc.date.none.fl_str_mv 2021-05-18T03:00:00Z
dc.identifier.none.fl_str_mv 10.3390/genes12050761
dc.relation.none.fl_str_mv https://figshare.com/articles/journal_contribution/Family-Based_Genome-Wide_Association_Study_of_Autism_Spectrum_Disorder_in_Middle_Eastern_Families/25756245
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Biological sciences
Genetics
autism spectrum disorder
neuropsychiatric disorders
genetic
genome-wide association
family
dc.title.none.fl_str_mv Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families
dc.type.none.fl_str_mv Text
Journal contribution
info:eu-repo/semantics/publishedVersion
text
contribution to journal
description <div><p>Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by abnormalities 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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Genes<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/genes12050761" target="_blank">https://dx.doi.org/10.3390/genes12050761</a></p>
eu_rights_str_mv openAccess
id Manara2_a6e055d9e96d062d097639deacf23ef7
identifier_str_mv 10.3390/genes12050761
network_acronym_str Manara2
network_name_str Manara2
oai_identifier_str oai:figshare.com:article/25756245
publishDate 2021
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rights_invalid_str_mv CC BY 4.0
spelling Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern FamiliesYasser Al-Sarraj (11721425)Eman Al-Dous (124700)Rowaida Z. Taha (8854754)Dina Ahram (18508161)Fouad Alshaban (6176771)Mohammed Tolfat (18508164)Hatem El-Shanti (492142)Omar M.E. Albagha (18508167)Biological sciencesGeneticsautism spectrum disorderneuropsychiatric disordersgeneticgenome-wide associationfamily<div><p>Autism spectrum disorder (ASD) is a neurodevelopmental disease characterized by abnormalities 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.</p><p> </p></div><h2>Other Information</h2> <p> Published in: Genes<br> License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.3390/genes12050761" target="_blank">https://dx.doi.org/10.3390/genes12050761</a></p>2021-05-18T03:00:00ZTextJournal contributioninfo:eu-repo/semantics/publishedVersiontextcontribution to journal10.3390/genes12050761https://figshare.com/articles/journal_contribution/Family-Based_Genome-Wide_Association_Study_of_Autism_Spectrum_Disorder_in_Middle_Eastern_Families/25756245CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/257562452021-05-18T03:00:00Z
spellingShingle Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families
Yasser Al-Sarraj (11721425)
Biological sciences
Genetics
autism spectrum disorder
neuropsychiatric disorders
genetic
genome-wide association
family
status_str publishedVersion
title Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families
title_full Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families
title_fullStr Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families
title_full_unstemmed Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families
title_short Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families
title_sort Family-Based Genome-Wide Association Study of Autism Spectrum Disorder in Middle Eastern Families
topic Biological sciences
Genetics
autism spectrum disorder
neuropsychiatric disorders
genetic
genome-wide association
family