Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD.

Détails

Ressource 1Demande d'une copie Sous embargo indéterminé.
Accès restreint UNIL
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_2A866AC1AFC8
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD.
Périodique
Nature communications
Auteur⸱e⸱s
Wang S., Wang B., Drury V., Drake S., Sun N., Alkhairo H., Arbelaez J., Duhn C., Bal V.H., Langley K., Martin J., Hoekstra P.J., Dietrich A., Xing J., Heiman G.A., Tischfield J.A., Fernandez T.V., Owen M.J., O'Donovan M.C., Thapar A., State M.W., Willsey A.J.
Collaborateur⸱rice⸱s
Tourette International Collaborative Genetics (TIC Genetics)
Contributeur⸱rice⸱s
Bromberg Y., Brown L.W., Cao X., Cheon K.A., Cheong K., Choi H., Coffey B.J., Deng L., Fremer C., Garcia-Delgar B., Gilbert D.L., Glover D., Grice D.E., Hagstrøm J., Hedderly T., Heyman I., Hong H.J., Huyser C., Kim H., Kim Y.K., Kim E., Kim Y.S., King R.A., Koh Y.J., Kook S., Kuperman S., Lee J., Leventhal B.L., Madruga-Garrido M., Mingbunjerdsuk D., Mir P., Morer A., Murphy T.L., Müller-Vahl K., Münchau A., Nasello C., Oh D.H., Plessen K.J., Roessner V., Shin E.Y., Song D.H., Song J., Thackray J.K., Visscher F., Zinner S.H.
ISSN
2041-1723 (Electronic)
ISSN-L
2041-1723
Statut éditorial
Publié
Date de publication
06/12/2023
Peer-reviewed
Oui
Volume
14
Numéro
1
Pages
8077
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
Autism spectrum disorder (ASD), Tourette syndrome (TS), and attention-deficit/hyperactivity disorder (ADHD) display strong male sex bias, due to a combination of genetic and biological factors, as well as selective ascertainment. While the hemizygous nature of chromosome X (Chr X) in males has long been postulated as a key point of "male vulnerability", rare genetic variation on this chromosome has not been systematically characterized in large-scale whole exome sequencing studies of "idiopathic" ASD, TS, and ADHD. Here, we take advantage of informative recombinations in simplex ASD families to pinpoint risk-enriched regions on Chr X, within which rare maternally-inherited damaging variants carry substantial risk in males with ASD. We then apply a modified transmission disequilibrium test to 13,052 ASD probands and identify a novel high confidence ASD risk gene at exome-wide significance (MAGEC3). Finally, we observe that rare damaging variants within these risk regions carry similar effect sizes in males with TS or ADHD, further clarifying genetic mechanisms underlying male vulnerability in multiple neurodevelopmental disorders that can be exploited for systematic gene discovery.
Mots-clé
Humans, Male, Female, Attention Deficit Disorder with Hyperactivity/genetics, Tourette Syndrome/genetics, Autistic Disorder/genetics, Autism Spectrum Disorder/genetics, Neurodevelopmental Disorders
Pubmed
Web of science
Open Access
Oui
Création de la notice
13/03/2024 11:15
Dernière modification de la notice
09/08/2024 14:53
Données d'usage