Identification of TYW3/CRYZ and FGD4 as susceptibility genes for amyotrophic lateral sclerosis
Open Access
- 1 December 2019
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Neurology Genetics
- Vol. 5 (6), e375
- https://doi.org/10.1212/nxg.0000000000000375
Abstract
Objective A 2-stage genome-wide association was conducted to explore the genetic etiology of amyotrophic lateral sclerosis (ALS) in the Chinese Han population. Methods Totally, 700 cases and 4,027 controls were genotyped in the discovery stage using Illumina Human660W-Quad BeadChips. Top associated single nucleotide polymorphisms from the discovery stage were then genotyped in an independent cohort with 884 cases and 5,329 controls. Combined analysis was conducted by combining all samples from the 2 stages. Results Two novel loci, 1p31 and 12p11, showed strong associations with ALS. These novel loci explained 2.2% of overall variance in disease risk. Expression quantitative trait loci searches identified TYW/CRYZ and FGD4 as risk genes at 1p13 and 12p11, respectively. Conclusions This study identifies novel susceptibility genes for ALS. Identification of TYW3/CRYZ in the current study supports the notion that insulin resistance may be involved in ALS pathogenesis, whereas FGD4 suggests an association with Charcot-Marie-Tooth disease.Keywords
This publication has 45 references indexed in Scilit:
- A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosisHuman Molecular Genetics, 2013
- MG53-induced IRS-1 ubiquitination negatively regulates skeletal myogenesis and insulin signallingNature Communications, 2013
- Credibility Analysis of Putative Disease-Causing Genes Using BioinformaticsPLOS ONE, 2013
- Genome-wide association analyses in Han Chinese identify two new susceptibility loci for amyotrophic lateral sclerosisNature Genetics, 2013
- A Hexanucleotide Repeat Expansion in C9ORF72 Is the Cause of Chromosome 9p21-Linked ALS-FTDNeuron, 2011
- Mutations in UBQLN2 cause dominant X-linked juvenile and adult-onset ALS and ALS/dementiaNature, 2011
- Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughsNature Medicine, 2004
- The impact of comorbid disease and injuries on resource use and expenditures in parkinsonismNeurology, 2003
- Quantifying heterogeneity in a meta-analysisStatistics in Medicine, 2002
- Longitudinal association of vascular and Alzheimer’s dementias, diabetes, and glucose toleranceNeurology, 1999