Details

Autor(en) / Beteiligte

• Fu, Jack M
• Satterstrom, F Kyle
• Peng, Minshi
• Brand, Harrison
• Collins, Ryan L
• Dong, Shan
• Wamsley, Brie
• Klei, Lambertus
• Wang, Lily
• Hao, Stephanie P
• Stevens, Christine R
• Cusick, Caroline
• Babadi, Mehrtash
• Banks, Eric
• Collins, Brett
• Dodge, Sheila
• Gabriel, Stacey B
• Gauthier, Laura
• Lee, Samuel K
• Liang, Lindsay
• Ljungdahl, Alicia
• Mahjani, Behrang
• Sloofman, Laura
• Smirnov, Andrey N
• Barbosa, Mafalda
• Betancur, Catalina
• Brusco, Alfredo
• Chung, Brian H Y
• Cook, Edwin H
• Cuccaro, Michael L
• Domenici, Enrico
• Ferrero, Giovanni Battista
• Gargus, J Jay
• Herman, Gail E
• Hertz-Picciotto, Irva
• Maciel, Patricia
• Manoach, Dara S
• Passos-Bueno, Maria Rita
• Persico, Antonio M
• Renieri, Alessandra
• Sutcliffe, James S
• Tassone, Flora
• Trabetti, Elisabetta
• Campos, Gabriele
• Cardaropoli, Simona
• Carli, Diana
• Chan, Marcus C Y
• Fallerini, Chiara
• Giorgio, Elisa
• Girardi, Ana Cristina
• Hansen-Kiss, Emily
• Lee, So Lun
• Lintas, Carla
• Ludena, Yunin
• Nguyen, Rachel
• Pavinato, Lisa
• Pericak-Vance, Margaret
• Pessah, Isaac N
• Schmidt, Rebecca J
• Smith, Moyra
• Costa, Claudia I S
• Trajkova, Slavica
• Wang, Jaqueline Y T
• Yu, Mullin H C
• Cutler, David J
• De Rubeis, Silvia
• Buxbaum, Joseph D
• Daly, Mark J
• Devlin, Bernie
• Roeder, Kathryn
• Sanders, Stephan J
• Talkowski, Michael E

Titel

Rare coding variation provides insight into the genetic architecture and phenotypic context of autism

Ist Teil von

• Nature genetics, 2022-09, Vol.54 (9), p.1320-1331

Ort / Verlag

United States: Nature Publishing Group

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Some individuals with autism spectrum disorder (ASD) carry functional mutations rarely observed in the general population. We explored the genes disrupted by these variants from joint analysis of protein-truncating variants (PTVs), missense variants and copy number variants (CNVs) in a cohort of 63,237 individuals. We discovered 72 genes associated with ASD at false discovery rate (FDR) ≤ 0.001 (185 at FDR ≤ 0.05). De novo PTVs, damaging missense variants and CNVs represented 57.5%, 21.1% and 8.44% of association evidence, while CNVs conferred greatest relative risk. Meta-analysis with cohorts ascertained for developmental delay (DD) (n = 91,605) yielded 373 genes associated with ASD/DD at FDR ≤ 0.001 (664 at FDR ≤ 0.05), some of which differed in relative frequency of mutation between ASD and DD cohorts. The DD-associated genes were enriched in transcriptomes of progenitor and immature neuronal cells, whereas genes showing stronger evidence in ASD were more enriched in maturing neurons and overlapped with schizophrenia-associated genes, emphasizing that these neuropsychiatric disorders may share common pathways to risk.