학술논문
Genome-wide association study of frontotemporal dementia identifies a C9ORF72 haplotype with a median of 12-G4C2 repeats that predisposes to pathological repeat expansions
Document Type
article
Author
Lianne M. Reus; Iris E. Jansen; Merel O. Mol; Fred van Ruissen; Jeroen van Rooij; Natasja M. van Schoor; Niccolò Tesi; Marcel J. T. Reinders; Martijn A. Huisman; Henne Holstege; Pieter Jelle Visser; Sterre C. M. de Boer; Marc Hulsman; Shahzad Ahmad; Najaf Amin; Andre G. Uitterlinden; Arfan Ikram; Cornelia M. van Duijn; Harro Seelaar; Inez H. G. B. Ramakers; Frans R. J. Verhey; Aad van der Lugt; Jurgen A. H. R. Claassen; Geert Jan Biessels; Peter Paul De Deyn; Philip Scheltens; Wiesje M. van der Flier; John C. van Swieten; Yolande A. L. Pijnenburg; Sven J. van der Lee
Source
Translational Psychiatry, Vol 11, Iss 1, Pp 1-8 (2021)
Subject
Language
English
ISSN
2158-3188
Abstract
Abstract Genetic factors play a major role in frontotemporal dementia (FTD). The majority of FTD cannot be genetically explained yet and it is likely that there are still FTD risk loci to be discovered. Common variants have been identified with genome-wide association studies (GWAS), but these studies have not systematically searched for rare variants. To identify rare and new common variant FTD risk loci and provide more insight into the heritability of C9ORF72-related FTD, we performed a GWAS consisting of 354 FTD patients (including and excluding N = 28 pathological repeat carriers) and 4209 control subjects. The Haplotype Reference Consortium was used as reference panel, allowing for the imputation of rare genetic variants. Two rare genetic variants nearby C9ORF72 were strongly associated with FTD in the discovery (rs147211831: OR = 4.8, P = 9.2 × 10−9, rs117204439: OR = 4.9, P = 6.0 × 10−9) and replication analysis (P