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NPJ Genom Med. 2019 Aug 23;4:19. doi: 10.1038/s41525-019-0093-8. eCollection 2019.

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

Collaborators (206)

Abbeduto L, Acampado J, Ace AJ, Albright C, Alessandri M, Amaral DG, Amatya A, Annett RD, Arriaga I, Bahl E, Balasubramanian A, Bardett N, Bashar A, Beaudet A, Beeson L, Bernier RA, Berry-Kravis E, Booker S, Brewster SJ, Brooks E, Butler ME, Butter EM, Callahan K, Camba A, Carpenter S, Carriero N, Cartner LA, Chatha AS, Chin W, Clark RD, Cohen C, Courchesne E, Cubells JF, Currin MH, Daniels AM, DeMarco L, Dennis MY, Dichter GS, Ding Y, Dinh H, Doan R, Doddapaneni H, Eldred S, Eng C, Erickson CA, Esler A, Fatemi A, J Fischer G, Fisk I, Fombonne EJ, Fox EA, Francis S, Friedman SL, Ganesan S, Garrett M, Gazestani V, Geisheker MR, Gerdts JA, Geschwind DH, Goin-Kochel RP, Griswold AJ, Grosvenor LP, Gruber AJ, Gulsrud AC, Gunderson J, Gutierrez A, Hale MN, Haley M, Hall JB, Hamer KE, Han B, Hanna N, Harkins C, Harris N, Hauf B, Hayes C, Hepburn SL, Herbert LM, Heyman M, Phillips BA, Horner S, Hu J, Huang-Storms LY, Hutter H, Istephanous D, Jacob S, Jensen W, Jones M, Jordy M, Juarez AP, Kanne S, Kaplan HE, Kent M, Kitaygorodsky A, Koomar T, Korchina V, Krentz AD, Schneider HL, Lamarche E, Landa RJ, Lash AE, Law JK, Lawson N, Layman K, Lechniak H, Lee S, Lee SJ, Coury DL, Martin CL, Li D, Li H, Lillie N, Liu X, Lord C, Mallardi MD, Manning P, Manoharan J, Marini R, Marzano G, Mason A, Matthews ET, McCracken JT, McKenzie AP, Momin Z, Morrier MJ, Murali S, Myers VJ, Neely J, Nessner C, Nicholson A, O'Brien K, O'Connor E, Ochoa-Lubinoff C, Orobio J, Ousley OY, Pacheco LD, Pandey J, Paolicelli AM, Pawlowski KG, Pierce KL, Piven J, Plate S, Popp M, Pramparo T, Prock LM, Qi H, Qiu S, Rachubinski AL, Rajbhandari K, Rana R, Remington R, Rice CE, Rigby C, Robertson BE, Roeder K, Rosenberg CR, Russo-Ponsaran N, Ruzzo E, Sahin M, Salomatov A, Sandhu S, Santangelo S, Sarver DE, Scherr J, Schultz RT, Schweers KA, Shah S, Shaikh T, Shocklee AD, Simon L, Simon AR, Singh V, Skinner S, Smith K, Smith CJ, Soorya LV, Soucy A, Stephens AN, Stock CM, Sutcliffe JS, Swanson A, Tafolla M, Takahashi N, Thomas T, Thomas C, Thompson S, Tjernagel J, Van Metre B, Veenstra-Vanderweele J, Vernoia BM, Wallace J, Walston CH, Wang J, Warren Z, Wasserburg L, White LC, White S, Wodka EL, Xu S, Yang WS, Yinger M, Yu T, Zang L, Zaydens H, Zhang H, Zhao H.

Author information

1Simons Foundation, New York, NY 10010 USA.
2Department of Systems Biology, Columbia University, New York, NY 10032 USA.
3Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195 USA.
4Department of Psychiatry, University of Iowa Carver College of Medicine, Iowa City, IA 52242 USA.
5Department of Molecular and Medical Genetics, Oregon Health & Science University, Portland, OR 97239 USA.
6Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX 77030 USA.
7Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195 USA.
8Department of Pediatrics, Columbia University Medical Center, New York, NY 10032 USA.
Contributed equally


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 ( 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

Conflict of interest statement

Competing interestsM.S. has received research funding from Roche, Novartis, Pfizer, Aucta, Navitor, Rugen, Ibsen, Neuren, LAM Therapeutics, Quadrant Biosciences and has served on the Scientific Advisory Board of Sage Therapeutics, Roche and Takeda. D.H.G. receives research funding from Takeda Pharmaceuticals, and consulting fees or equity participation for scientific advisory board work from Ovid Therapeutics, Axial Bio-therapeutics, Acurastem, and Falcon Computing. E.E.E. is on the scientific advisory board (SAB) of DNAnexus, Inc. All other authors declare no competing interests.

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