Accès ouvert déclaré
2022
article
Integrated gene analyses of de novo variants from 46,612 trios with autism and developmental disorders
Tianyun Wang, Chang N. Kim, Trygve E. Bakken, Madelyn A. Gillentine, Barbara Henning, Yafei Mao, Christian Gilissen, Tomasz J. Nowakowski, Evan E. Eichler, John Acampado, Alpha Amatya, Irina Astrovskaya, Asif Bashar, Elizabeth Brooks, Martin E. Butler, Lindsey A. Cartner, Wubin Chin, Wendy K. Chung, Amy M. Daniels, Pamela Feliciano, Chris Fleisch, Swami Ganesan, William B. Jensen, Alex Lash, Richard P. Marini, Vincent J. Myers, Eirene O'Connor, Chris Rigby, B. E. Robertson, Neelay Shah, Swapnil Shah, Emily Singer, LeeAnne Green Snyder, Alexandra N. Stephens, Jennifer Tjernagel, Brianna M. Vernoia, Natalia Volfovsky, L. Casey White, Alexander Hsieh, Yufeng Shen, Xueya Zhou, Tychele N. Turner, Ethan Bahl, Taylor Thomas, Leo Brueggeman, Tanner Koomar, Jacob J. Michaelson, Brian J. O’Roak, Rebecca Barnard, Richard A. Gibbs, Donna M. Muzny, Aniko Sabo, Kelli L. Baalman Ahmed, Matthew Siegel, Leonard Abbeduto, David G. Amaral, Brittani A. Hilscher, Deana Li, Kaitlin N. Smith, Samantha Thompson, Charles F. Albright, Eric Butter, Sara Eldred, Nathan Hanna, Mark Jones, Daniel L. Coury, Jessica Scherr, Taylor Pifher, Erin Roby, Brandy Dennis, Lorrin Higgins, Melissa A. Brown, Michael Alessandri, Anibal Gutierrez, Melissa N. Hale, Lynette M. Herbert, Hoa Lam Schneider, Giancarla David, Robert D. Annett, Dustin E. Sarver, Ivette Arriaga, Alexies Camba, Amanda C. Gulsrud, Monica Haley, James T. McCracken, Sophia Sandhu, Maira Tafolla, Wha S. Yang, Laura A. Carpenter, Catherine C. Bradley, Frampton Gwynette, Patricia Manning, Rebecca C. Shaffer, Carrie Thomas, Raphael Bernier, Emily A. Fox, Jennifer Gerdts, Micah Pepper, Theodore Ho, Daniel Cho, Joseph Piven, Holly Lechniak, Latha Soorya, Rachel Gordon, Allison Wainer, Lisa C. Yeh, Cesar Ochoa-Lubinoff, Nicole M. Russo‐Ponsaran, Elizabeth Berry‐Kravis, Stephanie Booker, Craig A. Erickson, Lisa M. Prock, Katherine G. Pawlowski, Emily T. Matthews, Stephanie Brewster, Margaret A. Hojlo, Evi Abada, Elena Lamarche, Shwetha C. Murali, William T. Harvey, Hannah E. Kaplan, Karen Pierce, Lindsey DeMarco, Susannah Horner, Juhi Pandey, Samantha Plate, Mustafa Şahin, Katherine D. Riley, Erin Carmody, Julia Constantini, Amy Esler, Ali Fatemi, Hanna Hutter, Rebecca Landa, Alexander P. McKenzie, Jason Neely, Vini Singh, Bonnie Van Metre, Ericka L. Wodka, Éric Fombonne, Lark Y. Huang-Storms, Lillian D. Pacheco, Sarah Mastel, Leigh A. Coppola, Sunday M. Francis, Andrea Jarrett, Suma Jacob, Natasha Lillie, Jaclyn Gunderson, Dalia Istephanous, Laura Simon, Ori Wasserberg, Angela L. Rachubinski, Cordelia Robinson Rosenberg, Stephen M. Kanne, Amanda D. Shocklee, Nicole Takahashi, Shelby L. Bridwell, Rebecca L. Klimczac, Melissa A. Mahurin, Hannah E. Cotrell, Cortaiga A. Grant, Samantha G. Hunter, Cora Taylor, Lauren K. Walsh, Katherine A. Dent, Andrew L. Mason, Anthony Sziklay, Christopher J. Smith
74Citations signalées, ce qui n’est pas une note de qualité
12Institutions déclarées
3Pays d’affiliation déclarés
Rattachement africain : us, cn, nl.
Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Most genetic studies consider autism spectrum disorder (ASD) and developmental disorder (DD) separately despite overwhelming comorbidity and shared genetic etiology. Here, we analyzed de novo variants (DNVs) from 15,560 ASD (6,557 from SPARK) and 31,052 DD trios independently and also combined as broader neurodevelopmental disorders (NDDs) using three models. We identify 615 NDD candidate genes (false discovery rate [FDR] < 0.05) supported by ≥1 models, including 138 reaching Bonferroni exome-wide significance ( P < 3.64e–7) in all models. The genes group into five functional networks associating with different brain developmental lineages based on single-cell nuclei transcriptomic data. We find no evidence for ASD-specific genes in contrast to 18 genes significantly enriched for DD. There are 53 genes that show mutational bias, including enrichments for missense ( n = 41) or truncating ( n = 12) DNVs. We also find 10 genes with evidence of male- or female-bias enrichment, including 4 X chromosome genes with significant female burden ( DDX3X , MECP2 , WDR45 , and HDAC8) . This large-scale integrative analysis identifies candidates and functional subsets of NDD genes.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Integrated gene analyses of de novo variants from 46,612 trios with autism and developmental disorders
- Date Crossref
- 11/11/2022
- Éditeur
- National Academy of Sciences
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Les institutions déclarées
Une affiliation ne permet pas de déduire la nationalité d’un auteur.
Les sujets associés
Autism Spectrum Disorder ResearchGenetics and Neurodevelopmental DisordersGenomic variations and chromosomal abnormalities