Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders
- Wang, T
- Hoekzema, K
- Vecchio, D
- Wu, H
- Sulovari, A
- Coe, BP
- Gillentine, MA
- Wilfert, AB
- Perez-Jurado, LA
- Kvarnung, M
- Sleyp, Y
- Earl, RK
- Rosenfeld, JA
- Geisheker, MR
- Han, L
- Du, B
- Barnett, C
- Thompson, E
- Shaw, M
- Carroll, R
- Friend, K
- Catford, R
- Palmer, EE
- Zou, X
- Ou, J
- Li, H
- Guo, H
- Gerdts, J
- Avola, E
- Calabrese, G
- Elia, M
- Greco, D
- Lindstrand, A
- Nordgren, A
- Anderlid, B-M
- Vandeweyer, G
- Van Dijck, A
- Van der Aa, N
- McKenna, B
- Hancarova, M
- Bendova, S
- Havlovicova, M
- Malerba, G
- Dalla Bernardina, B
- Muglia, P
- van Haeringen, A
- Hoffer, MJV
- Franke, B
- Cappuccio, G
- Delatycki, M
- Lockhart, PJ
- Manning, MA
- Liu, P
- Scheffer, IE
- Brunetti-Pierri, N
- Rommelse, N
- Amaral, DG
- Santen, GWE
- Trabetti, E
- Sedlacek, Z
- Michaelson, JJ
- Pierce, K
- Courchesne, E
- Kooy, RF
- Nordenskjold, M
- Romano, C
- Peeters, H
- Bernier, RA
- Gecz, J
- Xia, K
- Eichler, EE
DOIAbstract
Most 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 tr...
Add to ORKG