Variant "BIN1:n.127894615A>G"
Search result: 1 record
Variant information
Gene:
Variant:
BIN1:n.127894615A>G 
Genomic location:
chr2:127894615(hg19) 
HGVS:
SO Term RefSeq
BIN1-CYP27C1:n.127894615A>G
dbSNP ID:
GWAS trait:
Modifier statisitcs
Record:
Disorder:
Reference:
Effect type:
Expressivity(1)  
Modifier effect:
Risk factor(1)  
Detail:
  • 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:
    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.