Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes

Pamela Feliciano; Xueya Zhou; Irina Astrovskaya; Tychele N Turner; Tianyun Wang; Leo Brueggeman; Rebecca Barnard; Alexander Hsieh; LeeAnne Green Snyder; Donna M Muzny; Aniko Sabo; Richard A Gibbs; Evan E Eichler; Brian J O’Roak; Jacob J Michaelson; Natalia Volfovsky; Yufeng Shen; Wendy K Chung

doi:10.1038/s41525-019-0093-8

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Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes

Journal article

Open access

Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes

Pamela Feliciano, Xueya Zhou, Irina Astrovskaya, Tychele N Turner, Tianyun Wang, Leo Brueggeman, Rebecca Barnard, Alexander Hsieh, LeeAnne Green Snyder, Donna M Muzny, …

Npj genomic medicine, Vol.4(1), pp.19-14

12/01/2019

DOI: 10.1038/s41525-019-0093-8

PMCID: PMC6707204

PMID: 31452935

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Abstract

Autism spectrum disorder (ASD) is a genetically heterogeneous condition, caused by a combination of rare de novo and inherited variants as well as common variants in at least several hundred genes. However, significantly larger sample sizes are needed to identify the complete set of genetic risk factors. We conducted a pilot study for SPARK (SPARKForAutism.org) of 457 families with ASD, all consented online. Whole exome sequencing (WES) and genotyping data were generated for each family using DNA from saliva. We identified variants in genes and loci that are clinically recognized causes or significant contributors to ASD in 10.4% of families without previous genetic findings. In addition, we identified variants that are possibly associated with ASD in an additional 3.4% of families. A meta-analysis using the TADA framework at a false discovery rate (FDR) of 0.1 provides statistical support for 26 ASD risk genes. While most of these genes are already known ASD risk genes, BRSK2 has the strongest statistical support and reaches genome-wide significance as a risk gene for ASD ( p -value = 2.3e−06). Future studies leveraging the thousands of individuals with ASD who have enrolled in SPARK are likely to further clarify the genetic risk factors associated with ASD as well as allow accelerate ASD research that incorporates genetic etiology.

Autism spectrum disorders

Behavioural genetics

Medical genomics

Details

Title: Subtitle: Exome sequencing of 457 autism families recruited online provides evidence for autism risk genes
Creators: Pamela Feliciano - New York, NY 10010 USA
Xueya Zhou - New York, NY 10032 USA
Irina Astrovskaya - New York, NY 10010 USA
Tychele N Turner - Seattle, WA 98195 USA
Tianyun Wang - Seattle, WA 98195 USA
Leo Brueggeman - Iowa City, IA 52242 USA
Rebecca Barnard - Portland, OR 97239 USA
Alexander Hsieh - New York, NY 10032 USA
LeeAnne Green Snyder - New York, NY 10010 USA
Donna M Muzny - Houston, TX 77030 USA
Aniko Sabo - Houston, TX 77030 USA
Richard A Gibbs - Houston, TX 77030 USA
Evan E Eichler - Seattle, WA 98195 USA
Brian J O’Roak - Portland, OR 97239 USA
Jacob J Michaelson - Iowa City, IA 52242 USA
Natalia Volfovsky - New York, NY 10010 USA
Yufeng Shen - New York, NY 10032 USA
Wendy K Chung - New York, NY 10010 USA
Resource Type: Journal article
Publication Details: Npj genomic medicine, Vol.4(1), pp.19-14
DOI: 10.1038/s41525-019-0093-8
PMID: 31452935
PMCID: PMC6707204
NLM abbreviation: NPJ Genom Med
ISSN: 2056-7944
eISSN: 2056-7944
Publisher: Nature Publishing Group UK; London
Grant note: ; MH105527; DC014489 / ; SFARI #608045; SFARI #608045; SFARI #608045 / ; R01MH101221; 1K99MH117165; R01MH101221; R01MH101221 / ; 1K99MH117165; MH105527; DC014489 / ;
Language: English
Date published: 12/01/2019
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Communication Sciences and Disorders; Psychiatry; Iowa Neuroscience Institute
Record Identifier: 9984070347702771

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