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rs12608932

From SNPedia

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Make rs12608932(A;A)
Make rs12608932(A;C)
Make rs12608932(C;C)
ReferenceGRCh38 38.1/141
Chromosome19
Position17641880
GeneUNC13A
is asnp
is mentioned by
dbSNPrs12608932
dbSNP (old)rs12608932
ClinGenrs12608932
ebirs12608932
HLIrs12608932
Exacrs12608932
Varsomers12608932
Maprs12608932
PheGenIrs12608932
Biobankrs12608932
1000 genomesrs12608932
hgdprs12608932
ensemblrs12608932
gopubmedrs12608932
geneviewrs12608932
scholarrs12608932
googlers12608932
pharmgkbrs12608932
gwascentralrs12608932
openSNPrs12608932
23andMers12608932
23andMe allrs12608932
SNP Nexus

SNPshotrs12608932
SNPdbers12608932
MSV3drs12608932
GWAS Ctlgrs12608932
GMAF0.4325
Max Magnitude
? (A;A) (A;C) (C;C) 28
GWAS snp
PMID [PMID 19734901]
Trait Amyotrophic lateral sclerosis
Title Genome-wide association study identifies 19p13.3 (UNC13A) and 9p21.2 as susceptibility loci for sporadic amyotrophic lateral sclerosis
Risk Allele
P-val 3E-14
Odds Ratio 1.25 [NR]
OMIM105400
Desc
Variant
Relatedalso

rs12608932 is a SNP located in an intron of the UNC13A gene which encodes UNC13A, a protein involved with regulation of neurotransmitters like glutamate at central and neuromuscular synpases.

rs12608932(C, reference allele: A) was identified as a risk allele associated with sporadic amyotrophic lateral sclerosis (sALS) or Lou Gehrig’s disease in a two-stage association study with individuals of European ancestry. An initial genome-wide study (2,323 case and 9,013 control subjects) identified SNPs that exhibited P-values less than 1.0x10-4, including rs12608932 (P =1.30x10-9, OR=1.25). These SNPs were further evaluated in a second, independent cohort of individuals (2,532 affected individuals and 5,940 controls). This SNP exhibited significant association in the replication round (P=1.86x10-6, OR=1.20 replication round) with an overall combined P=2.50x10-14. [PMID 19734901]

Two replication studies examining the association of including rs12608932 did not identify any significant association with sALS. The first of these studies was performed with patients from France (285 cases and 285 controls) were genotyped for rs12608932 exhibited P=0.85. [PMID 20385924] The second examined two separate populations of Japanese (1179 cases/1645 controls) and Chinese (684 cases/830 controls) ancestry and found no significant association of rs12608932 with sALS (P=0.67 OR=1.02 for Japanese and P=0.73 OR=1.02 for Chinese). [PMID 21295378] Additionally, the allele frequencies differ between the Eastern Asian population (MAF in Japanese controls: 0.741, cases: 0.746; in Chinese controls: 0.675, cases: 0.681) and the European ancestry population in the initial GWA study that identified rs12608932 as associated with sALS. The minor allele frequency in this study was 0.395 in patients and 0.342 in controls in the first GWAS stage and 0.369 in patients and 0.337 in controls in the second-stage of the study. [PMID 19734901] In both the French and East Asian replication studies, the sample sizes may have been too small to exclude rs12608932(C) as a risk allele for sALS. For example, the power of the Chinese population study was only 63%.

A more recent smaller-scale replication study did identify an association of rs12608932 with sALS in patients of Dutch ancestry (P=0.001). Additionally, the authors collected data on the survivability of patients with sALS and control individuals (of Dutch, Swedish, and Belgian descent) from the previous GWAS which initially associated rs12608932 with ALS [PMID 19734901]. This study showed a weak association with survivability and rs12608932 (P<0.001) when fit to a recessive model. Patients homozygous for the minor allele of rs12608932 (CC) exhibited shorter survival after ALS onset than patients AC or AA by 5 and 10 months in the Dutch population and GWAS cohort, respectively. [PMID 22118904]


[PMID 22118904] UNC13A is a modifier of survival in amyotrophic lateral sclerosis


[PMID 22509407OA-icon.png] Mapping of Gene Expression Reveals CYP27A1 as a Susceptibility Gene for Sporadic ALS


GET Evidence
rs12608932
aa_change
aa_change_short
impact pathogenic
qualified_impact Insufficiently evaluated pathogenic
overall_frequency 0.34375
summary



GWAS snp
PMID [PMID 22959728OA-icon.png]
Trait Amyotrophic lateral sclerosis
Title Age of onset of amyotrophic lateral sclerosis is modulated by a locus on 1p34.1.
Risk Allele C
P-val 5E-8
Odds Ratio 1.37 [1.21-1.56]


[PMID 22921269OA-icon.png] UNC13A influences survival in Italian amyotrophic lateral sclerosis patients: a population-based study.

GWAS snp
PMID [PMID 24256812OA-icon.png]
Trait Amyotrophic lateral sclerosis (sporadic)
Title A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis.
Risk Allele
P-val 6E-6
Odds Ratio NR NR