Gene "BIN1"
Found 2 records
Gene information
Gene symbol:
BIN1
See related:
Ensembl: ENSG00000136717, Gene ID: 274
Additive variants :
Undetected
Genetic interaction partners
No data
Modifier statisitcs
Record:
2 
Disorder:
1 
Vriant:
2 
Reference:
2 
Effect type:
Expressivity(2)  
Modifier effect:
Altered onset time(1) ,Risk factor(1)  
Details：
  • Variant 1:
    BIN1:n.127894615A>G
    Gene:
    BIN1
    Genomic location:
    chr2:127894615
    dbSNP ID:
    rs744373
    Target disease:
    Alzheimer's Disease(DOID_10652)
    Effect type:
    Expressivity 
    Modifier effect:
    Risk factor 
    Evidence:
    P=3.8×10(-20) 
    Effect:
    The variant near BIN1 (rs744373) as a LOAD risk modifier
    Reference:
    PMID21321396
    Title:
    Replication of BIN1 association with Alzheimer's disease and evaluation of genetic interactions.
    Species studied:
    Human
    Abstract:
    The most recent late-onset Alzheimer's disease (LOAD) genome-wide association study revealed genome-wide significant association of two new loci: rs744373 near BIN1 (p = 1.6 × 10-11) and rs597668 near EXOC3L2/BLOC1S3/MARK4 (p = 6.5 × 10-9). We have genotyped these variants in a large (3,287 LOAD, 4,396 controls), independent dataset comprising eleven case-control series from the USA and Europe. We performed meta-analyses of the association of these variants with LOAD and also tested for association using logistic regression adjusted by age-at-diagnosis, gender, and APOE ε4 status. Meta-analysis results showed no evidence of series heterogeneity and logistic regression analysis successfully replicated the association of BIN1 (rs744373) with LOAD with an odds ratio (OR = 1.17, p = 1.1 × 10-4) comparable to that previously reported (OR = 1.15). The variant near EXOC3L2 (rs597668) showed only suggestive association with LOAD (p = 0.09) after correcting for the presence of the APOE ε4 allele. Addition of our follow-up data to the results previously reported increased the strength of evidence for association with BIN1 (11,825 LOAD, 32,570 controls, rs744373 Fisher combined p = 3.8 × 10-20). We also tested for epistatic interaction between these variants and APOE ε4 as well as with the previously replicated LOAD GWAS genes (CLU: rs11136000, CR1: rs3818361, and PICALM: rs3851179). No significant interactions between these genes were detected. In summary, we provide additional evidence for the variant near BIN1 (rs744373) as a LOAD risk modifier, but our results indicate that the effect of EXOC3L2 independent of APOE ε4 should be studied further.
  • Variant 2:
    BIN1:n.127618436G>A
    Gene:
    BIN1
    Genomic location:
    chr2:127618436
    dbSNP ID:
    rs13403026
    Target disease:
    Alzheimer's Disease(DOID_10652)
    Effect type:
    Expressivity 
    Modifier effect:
    Altered onset time 
    Evidence:
    P=0.0001 
    Effect:
    The BIN1 locus may modify the AAO of GBA-associated PD.
    Reference:
    PMID26233692
    Title:
    The Alzheimer disease BIN1 locus as a modifier of GBA-associated Parkinson disease.
    Species studied:
    Human
    Abstract:
    GBA mutations are among the most common genetic risk factors for Parkinson disease (PD) worldwide. We aimed to identify genetic modifiers of the age at onset (AAO) in GBA-associated PD. The study included a genome-wide discovery phase, including a cohort of 79 patients with the GBA p.N370S mutation, and candidate validation and replication analyses of 8 SNPs in patients with mild (n = 113) and severe (n = 41) GBA mutations. Genotyping was performed using the Affymetrix human SNP 6.0 array and TaqMan assays. In the genome-wide phase, none of the SNPs passed the genome-wide significance threshold. Eight SNPs were selected for further analysis from the top hits. In all GBA-associated PD patients (n = 153), the BIN1 rs13403026 minor allele was associated with an older AAO (12.4 ± 5.9 years later, p = 0.0001), compared to patients homozygous for the major allele. Furthermore, the AAO was 10.7 ± 6.8 years later in patients with mild GBA mutations, (p = 0.005, validation group), and 17.1 ± 2.5 years later in patients with severe GBA mutations (p = 0.01, replication). Our results suggest that alterations in the BIN1 locus, previously associated with Alzheimer disease, may modify the AAO of GBA-associated PD. More studies in other populations are required to examine the role of BIN1-related variants in GBA-associated PD.