A case-control collapsing analysis identifies epilepsy genes implicated in trio sequencing studies focused on de novo mutations

Xiaolin Zhu, Raghavendra Padmanabhan, Brett Copeland, Joshua Bridgers, Zhong Ren, Sitharthan Kamalakaran, Ailbhe O'Driscoll-Collins, Samuel F Berkovic, Ingrid E Scheffer, Annapurna Poduri, Davide Mei, Renzo Guerrini, Daniel H Lowenstein, Andrew S Allen, Erin L Heinzen and David B Goldstein

PLOS Genetics, 2017, vol. 13, issue 11, 1-12

Abstract: Trio exome sequencing has been successful in identifying genes with de novo mutations (DNMs) causing epileptic encephalopathy (EE) and other neurodevelopmental disorders. Here, we evaluate how well a case-control collapsing analysis recovers genes causing dominant forms of EE originally implicated by DNM analysis. We performed a genome-wide search for an enrichment of "qualifying variants" in protein-coding genes in 488 unrelated cases compared to 12,151 unrelated controls. These "qualifying variants" were selected to be extremely rare variants predicted to functionally impact the protein to enrich for likely pathogenic variants. Despite modest sample size, three known EE genes (KCNT1, SCN2A, and STXBP1) achieved genome-wide significance (p

Date: 2017
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007104 (text/html)
https://journals.plos.org/plosgenetics/article/fil ... 07104&type=printable (application/pdf)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:plo:pgen00:1007104

DOI: 10.1371/journal.pgen.1007104

Access Statistics for this article

More articles in PLOS Genetics from Public Library of Science
Bibliographic data for series maintained by plosgenetics ().