Show simple item record

dc.contributor.authorWang, T
dc.contributor.authorHoekzema, K
dc.contributor.authorVecchio, D
dc.contributor.authorWu, H
dc.contributor.authorSulovari, A
dc.contributor.authorCoe, BP
dc.contributor.authorGillentine, MA
dc.contributor.authorWilfert, AB
dc.contributor.authorPerez-Jurado, LA
dc.contributor.authorKvarnung, M
dc.contributor.authorSleyp, Y
dc.contributor.authorEarl, RK
dc.contributor.authorRosenfeld, JA
dc.contributor.authorGeisheker, MR
dc.contributor.authorHan, L
dc.contributor.authorDu, B
dc.contributor.authorBarnett, C
dc.contributor.authorThompson, E
dc.contributor.authorShaw, M
dc.contributor.authorCarroll, R
dc.contributor.authorFriend, K
dc.contributor.authorCatford, R
dc.contributor.authorPalmer, EE
dc.contributor.authorZou, X
dc.contributor.authorOu, J
dc.contributor.authorLi, H
dc.contributor.authorGuo, H
dc.contributor.authorGerdts, J
dc.contributor.authorAvola, E
dc.contributor.authorCalabrese, G
dc.contributor.authorElia, M
dc.contributor.authorGreco, D
dc.contributor.authorLindstrand, A
dc.contributor.authorNordgren, A
dc.contributor.authorAnderlid, B-M
dc.contributor.authorVandeweyer, G
dc.contributor.authorVan Dijck, A
dc.contributor.authorVan der Aa, N
dc.contributor.authorMcKenna, B
dc.contributor.authorHancarova, M
dc.contributor.authorBendova, S
dc.contributor.authorHavlovicova, M
dc.contributor.authorMalerba, G
dc.contributor.authorDalla Bernardina, B
dc.contributor.authorMuglia, P
dc.contributor.authorvan Haeringen, A
dc.contributor.authorHoffer, MJV
dc.contributor.authorFranke, B
dc.contributor.authorCappuccio, G
dc.contributor.authorDelatycki, M
dc.contributor.authorLockhart, PJ
dc.contributor.authorManning, MA
dc.contributor.authorLiu, P
dc.contributor.authorScheffer, IE
dc.contributor.authorBrunetti-Pierri, N
dc.contributor.authorRommelse, N
dc.contributor.authorAmaral, DG
dc.contributor.authorSanten, GWE
dc.contributor.authorTrabetti, E
dc.contributor.authorSedlacek, Z
dc.contributor.authorMichaelson, JJ
dc.contributor.authorPierce, K
dc.contributor.authorCourchesne, E
dc.contributor.authorKooy, RF
dc.contributor.authorNordenskjold, M
dc.contributor.authorRomano, C
dc.contributor.authorPeeters, H
dc.contributor.authorBernier, RA
dc.contributor.authorGecz, J
dc.contributor.authorXia, K
dc.contributor.authorEichler, EE
dc.date.accessioned2020-11-17T04:00:21Z
dc.date.available2020-11-17T04:00:21Z
dc.date.issued2020-10-01
dc.identifierpii: 10.1038/s41467-020-18723-y
dc.identifier.citationWang, T., Hoekzema, K., Vecchio, D., Wu, H., Sulovari, A., Coe, B. P., Gillentine, M. A., Wilfert, A. B., Perez-Jurado, L. A., Kvarnung, M., Sleyp, Y., Earl, R. K., Rosenfeld, J. A., Geisheker, M. R., Han, L., Du, B., Barnett, C., Thompson, E., Shaw, M. ,... Eichler, E. E. (2020). Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders. NATURE COMMUNICATIONS, 11 (1), https://doi.org/10.1038/s41467-020-18723-y.
dc.identifier.issn2041-1723
dc.identifier.urihttp://hdl.handle.net/11343/251667
dc.description.abstractMost genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.
dc.languageEnglish
dc.publisherNATURE RESEARCH
dc.titleLarge-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
dc.typeJournal Article
dc.identifier.doi10.1038/s41467-020-18723-y
melbourne.affiliation.departmentPaediatrics (RCH)
melbourne.affiliation.departmentMelbourne School of Population and Global Health
melbourne.affiliation.departmentMedicine and Radiology
melbourne.source.titleNature Communications
melbourne.source.volume11
melbourne.source.issue1
dc.rights.licenseCC BY
melbourne.elementsid1467935
melbourne.contributor.authorLockhart, Paul
melbourne.contributor.authorDelatycki, Martin
melbourne.contributor.authorScheffer, Ingrid
dc.identifier.eissn2041-1723
pubs.acceptance.date2020-09-04
melbourne.accessrightsOpen Access


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record