Discovery of EQTL Alleles Associated with Autism Spectrum Disorder: A Case-Control Study

Overview

Journal J Autism Dev Disord

Publisher Springer

Date 2022 Jun 23

PMID 35739433

Authors

Allison R Hickman

Bradley Selee

Rini Pauly

Benafsh Husain

Yuqing Hang

Frank Alex Feltus

Affiliations

Soon will be listed here.

Abstract

Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder characterized by challenges in social communication as well as repetitive or restrictive behaviors. Many genetic associations with ASD have been identified, but most associations occur in a fraction of the ASD population. Here, we searched for eQTL-associated DNA variants with significantly different allele distributions between ASD-affected and control. Thirty significant DNA variants associated with 174 tissue-specific eQTLs from ASD individuals in the SPARK project were identified. Several significant variants fell within brain-specific regulatory regions or had been associated with a significant change in gene expression in the brain. These eQTLs are a new class of biomarkers that could control the myriad of brain and non-brain phenotypic traits seen in ASD-affected individuals.

Citing Articles

Unveiling promising drug targets for autism spectrum disorder: insights from genetics, transcriptomics, and proteomics.

Jiang R, Huang W, Qiu X, Chen J, Luo R, Zeng R Brief Bioinform. 2024; 25(4).

PMID: 39038939 PMC: 11262832. DOI: 10.1093/bib/bbae353.

eQTL colocalization analysis highlights novel susceptibility genes in Autism Spectrum Disorders (ASD).

Dominguez-Alonso S, Carracedo A, Rodriguez-Fontenla C Transl Psychiatry. 2023; 13(1):336.

PMID: 37907504 PMC: 10618232. DOI: 10.1038/s41398-023-02621-0.

References

Abrahams B, Arking D, Campbell D, Mefford H, Morrow E, Weiss L . SFARI Gene 2.0: a community-driven knowledgebase for the autism spectrum disorders (ASDs). Mol Autism. 2013; 4(1):36. PMC: 3851189. DOI: 10.1186/2040-2392-4-36. View

Abrahams B, Geschwind D . Advances in autism genetics: on the threshold of a new neurobiology. Nat Rev Genet. 2008; 9(5):341-55. PMC: 2756414. DOI: 10.1038/nrg2346. View

Albert F, Kruglyak L . The role of regulatory variation in complex traits and disease. Nat Rev Genet. 2015; 16(4):197-212. DOI: 10.1038/nrg3891. View

An Y, Zhang L, Liu W, Jiang Y, Chen X, Lan X . De novo variants in the Helicase-C domain of CHD8 are associated with severe phenotypes including autism, language disability and overgrowth. Hum Genet. 2020; 139(4):499-512. DOI: 10.1007/s00439-020-02115-9. View

Auton A, Brooks L, Durbin R, Garrison E, Kang H, Korbel J . A global reference for human genetic variation. Nature. 2015; 526(7571):68-74. PMC: 4750478. DOI: 10.1038/nature15393. View

Berkel S, Marshall C, Weiss B, Howe J, Roeth R, Moog U . Mutations in the SHANK2 synaptic scaffolding gene in autism spectrum disorder and mental retardation. Nat Genet. 2010; 42(6):489-91. DOI: 10.1038/ng.589. View

Betancur C . Etiological heterogeneity in autism spectrum disorders: more than 100 genetic and genomic disorders and still counting. Brain Res. 2010; 1380:42-77. DOI: 10.1016/j.brainres.2010.11.078. View

Bhat A . Motor Impairment Increases in Children With Autism Spectrum Disorder as a Function of Social Communication, Cognitive and Functional Impairment, Repetitive Behavior Severity, and Comorbid Diagnoses: A SPARK Study Report. Autism Res. 2020; 14(1):202-219. PMC: 8176850. DOI: 10.1002/aur.2453. View

Bi X, Liu Y, Jiang Q, Shu Q, Sun Q, Dai J . The Diagnosis of Autism Spectrum Disorder Based on the Random Neural Network Cluster. Front Hum Neurosci. 2018; 12:257. PMC: 6028564. DOI: 10.3389/fnhum.2018.00257. View

10.

Bolton P, Macdonald H, Pickles A, Rios P, Goode S, Crowson M . A case-control family history study of autism. J Child Psychol Psychiatry. 1994; 35(5):877-900. DOI: 10.1111/j.1469-7610.1994.tb02300.x. View

11.

Boyle E, Li Y, Pritchard J . An Expanded View of Complex Traits: From Polygenic to Omnigenic. Cell. 2017; 169(7):1177-1186. PMC: 5536862. DOI: 10.1016/j.cell.2017.05.038. View

12.

Caceres A, Esko T, Pappa I, Gutierrez A, Lopez-Espinosa M, Llop S . Ancient Haplotypes at the 15q24.2 Microdeletion Region Are Linked to Brain Expression of MAN2C1 and Children's Intelligence. PLoS One. 2016; 11(6):e0157739. PMC: 4927142. DOI: 10.1371/journal.pone.0157739. View

13.

Chang J, Kochel R . Vaccine Hesitancy and Attributions for Autism among Racially and Ethnically Diverse Groups of Parents of Children with Autism Spectrum Disorder: A Pilot Study. Autism Res. 2020; 13(10):1790-1796. DOI: 10.1002/aur.2339. View

14.

Chau K, Zhang P, Urresti J, Amar M, Pramod A, Chen J . Full-length isoform transcriptome of the developing human brain provides further insights into autism. Cell Rep. 2021; 36(9):109631. PMC: 8437376. DOI: 10.1016/j.celrep.2021.109631. View

15.

Cortese S, Vincenzi B . Obesity and ADHD: clinical and neurobiological implications. Curr Top Behav Neurosci. 2011; 9:199-218. DOI: 10.1007/7854_2011_154. View

16.

Croen L, Zerbo O, Qian Y, Massolo M, Rich S, Sidney S . The health status of adults on the autism spectrum. Autism. 2015; 19(7):814-23. DOI: 10.1177/1362361315577517. View

17.

Di Martino A, OConnor D, Chen B, Alaerts K, Anderson J, Assaf M . Enhancing studies of the connectome in autism using the autism brain imaging data exchange II. Sci Data. 2017; 4:170010. PMC: 5349246. DOI: 10.1038/sdata.2017.10. View

18.

Dimas A, Deutsch S, Stranger B, Montgomery S, Borel C, Attar-Cohen H . Common regulatory variation impacts gene expression in a cell type-dependent manner. Science. 2009; 325(5945):1246-50. PMC: 2867218. DOI: 10.1126/science.1174148. View

19.

Doshi-Velez F, Ge Y, Kohane I . Comorbidity clusters in autism spectrum disorders: an electronic health record time-series analysis. Pediatrics. 2013; 133(1):e54-63. PMC: 3876178. DOI: 10.1542/peds.2013-0819. View

20.

M Durand C, Betancur C, Boeckers T, Bockmann J, Chaste P, Fauchereau F . Mutations in the gene encoding the synaptic scaffolding protein SHANK3 are associated with autism spectrum disorders. Nat Genet. 2006; 39(1):25-7. PMC: 2082049. DOI: 10.1038/ng1933. View