UNC13A confers risk for sporadic ALS and influences survival in a Spanish cohort

Abstract

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Common polymorphisms of chemokine (C‐X3‐C motif) receptor 1 gene modify amyotrophic lateral sclerosis outcome: A population‐based study

“…In the past few years, several studies of genetic modifiers of ALS phenotype or prognosis have been conducted. The rs12608932 CC genotype of the UNC13A gene has been demonstrated in several populations to be related to a shorter survival than the A/C and A/A genotypes . More recently, a large international meta‐analysis of GWAS found 2 loci (at 10q23, SNP rs139550538 and at 1p36, rs2412208) in which the presence of the minor alleles in the homozygous state were significantly associated with a reduction of survival of 7 and 4 months, respectively .…”

“…The rs12608932 CC genotype of the UNC13A gene has been demonstrated in several populations to be related to a shorter survival than the A/C and A/A genotypes. [24][25][26][27] More recently, a large international meta-analysis of GWAS found 2 loci (at 10q23, SNP rs139550538 and at 1p36, rs2412208) in which the presence of the minor alleles in the homozygous state were significantly associated with a reduction of survival of 7 and 4 months, respectively. 28 Also, the presence of at least 1 minor allele of the rs3011225 SNP located on chromosome 1p34.1 was associated with earlier age of onset in a meta-analysis of 13 GWAS cohorts.…”

Neuron-Microglia Interactions in Motor Neuron Degeneration. The Inflammatory Hypothesis in Amyotrophic Lateral Sclerosis Revisited

“…Of these, defects in six genes have been found to be main causes of the disease [33], and a growing number of genes have been associated with ALS susceptibility, progression or prevalence. [34][35][36][37][38] ( Table 1) Multiple mutations of a sole gene also lead to graded phenotypic affectations.…”

Rare genetic variation in UNC13A may modify survival in amyotrophic lateral sclerosis

“…The association is independent from that of common variation at rs12608932, which is associated with ALS risk and survival (4,6,18). We have not found rare SNVs modifying ALS risk in the EPHA4 or KIFAP3 genes.…”

“…The common rs12608932 SNV in UNC13A has been identified as both an ALS risk (19,20) and survival (6,18) variant. This study adds to the body of evidence supporting UNC13A variants as important in modifying ALS survival and suggests that the pathological effect may not be confined to a function of rs12608932 or an associated variant.…”