Have questions? Visit https://www.reddit.com/r/SNPedia

rs10504861

From SNPedia

rs10504861 is a SNP located on Chromosome 8q21 that was found to be associated with elevated incidence of migraine without aura in genome-wide association studies (GWAS).
Orientationminus
Stabilizedminus
Geno Mag Summary
(A;A) 2 Reduced risk of migraine without aura
(A;G) 2 Reduced risk of migraine without aura
(G;G) 1 Major allele, normal risk of migraine
ReferenceGRCh38 38.1/141
Chromosome8
Position88535703
is asnp
is mentioned by
dbSNPrs10504861
ebirs10504861
HLIrs10504861
Exacrs10504861
Varsomers10504861
Maprs10504861
PheGenIrs10504861
hapmaprs10504861
1000 genomesrs10504861
hgdprs10504861
ensemblrs10504861
gopubmedrs10504861
geneviewrs10504861
scholarrs10504861
googlers10504861
pharmgkbrs10504861
gwascentralrs10504861
openSNPrs10504861
23andMers10504861
23andMe allrs10504861
SNP Nexus

SNPshotrs10504861
SNPdbers10504861
MSV3drs10504861
GWAS Ctlgrs10504861
GMAF0.1974
Max Magnitude2
GWAS snp
PMID [PMID 23793025OA-icon.png]
Trait Migraine without aura
Title Genome-wide meta-analysis identifies new susceptibility loci for migraine.
Risk Allele G
P-val 1E-8
Odds Ratio 1.16 [1.10-1.23]
? (A;A) (A;G) (G;G) 28

rs10504861 is a SNP located on Chromosome 8q21 that was found to be associated with elevated incidence of migraine without aura in genome-wide association studies (GWAS). Migraine is a common but often incapacitating disease that affects up to 20% of the population, and affects 3-4 times as many women as men [PMID 16426991OA-icon.png]. Migraine can be classified into two main types: migraine with auras and migraines without auras. Migraine with auras accounts for a third of cases, where individuals experience a transient neurological symptom such as a visual, sensory, language or motor disturbance prior to an impending migraine attack [PMID 14979299]. Migraines are thought to be caused by a mixture of genetic and environmental factors, with about two-thirds of patients reporting family history [PMID 20572569].

rs10504861’s association with migraine without aura was first identified in a meta-analysis GWAS published in 2013[PMID 23793025OA-icon.png], which pooled 23,285 cases and 95,425 controls. rs10504861 was shown to be significantly associated with migraine without aura, where the minor allele (T) is protective (p = 1.32 × 10−8, OR = 0.86; 95%CI: 0.81 – 0.91). However, this SNP did not pass genome-wide significance threshold when studying its association with all migraine cases (p-value not reported).

A smaller clinic-based replication study was conducted in Spain in 2014 [PMID 25388962], which recruited 512 migraine cases and 535 ethnically-matched controls; females made up three-quarters of both groups. 13 SNPs were genotyped in an attempt to replicate previous findings. Interestingly, this study reports a significant association between the rs10504861 SNP and migraine (with and without auras) under a recessive model (corrected p = 0.0288, OR = 0.26, 95%CI not reported). The minor allele is similarly shown to be protective.

A similar small-scale replication study was performed in Denmark in 2015 [PMID 25667298]. This study recruited 1806 cases and 6415 controls, and performed genotyping on 12 SNPs. In this study, rs10504861 was not found to be statistically associated with migraines without aura (p=0.95, OR = 0.99, 95%CI: 0.89-1.14) or migraines in general (p=0.5, OR=0.97, 95%CI: 0.88-1.07).

The inconclusive results above suggest that rs10504861 may only be associated with a specific sub-classification of migraine, where statistical significance is reached only in a very large cohort study. A hypothesis-driven study on a more detailed sub-classification of migraine in women suggests that rs10504861 is preferentially associated with active migraines [PMID 24852292OA-icon.png].

The SNP is located 200kb away from the matrix metalloproteinase MMP16. Metalloproteinases are a diverse family of protease enzymes involved in the breakdown of extracellular matrix in normal physiological processes. Notably, the protein encoded by MMP16, MT3-MMP, cleaves low-density lipoprotein receptor protein, LRP1 [PMID 14645246]. A SNP within LRP1 (rs11172113) has previously been reported to be associated with migraine in a genome-wide association study [PMID 21666692OA-icon.png]. In addition, MT3-MMP has recently been shown to be involved in basal NgR1 (Nogo-66 receptor) shedding in cortical neurons, thereby increasing axonal and synaptic plasticity [PMID 22311207]. Though no conclusive evidence exist for the mechanism mitigating association of MMP16 to migraines, these two implications offer plausible explanations for biological implication of rs10504861 in migraine pathology.

[PMID 23793025OA-icon.png] Genome-wide meta-analysis identifies new susceptibility loci for migraine.

[PMID 20572569] Migraine update. Diagnosis and treatment.

[PMID 22311207] The Nogo-66 receptor family in the intact and diseased CNS.

[PMID 21666692OA-icon.png] Genome-wide association study reveals three susceptibility loci for common migraine in the general population.

[PMID 24852292OA-icon.png] Selectivity in genetic association with sub-classified migraine in women.

[PMID 25667298] The association between candidate migraine susceptibility loci and severe migraine phenotype in a clinical sample.

[PMID 16426991OA-icon.png] Chronic disorders with episodic manifestations: focus on epilepsy and migraine.

[PMID 14979299] The International Classification of Headache Disorders: 2nd edition.

[PMID 14645246] The low density lipoprotein receptor–related protein LRP is regulated by membrane type-1 matrix metalloproteinase (MT1-MMP) proteolysis in malignant cells.

[PMID 25388962] Replication study of previous migraine genome-wide association study findings in a Spanish sample of migraine with aura.

[PMID 26231841OA-icon.png] Association of genetic loci for migraine susceptibility in the she people of China