rs744373

badMag 5.5

This is a intron variant variant in the BIN1 gene.

Key Literature Trait Associations

Alzheimer's Disease

The C allele of rs744373 in BIN1 is robustly associated with late-onset Alzheimer's disease, with a per-allele odds ratio of approximately 1.17–1.19 across multiple large GWAS and meta-analyses. This association has been replicated in European and, to a lesser extent, East Asian populations, and is among the most consistently validated non-APOE AD risk loci. A 2017 updated meta-analysis of 22 studies (11,832 cases, 18,133 controls) confirmed significance in both Caucasian and Asian cohorts. A 2024 multi-ancestry meta-analysis (n > 523,000) extended the association to an all-cause dementia endpoint at p = 2×10⁻¹⁷.

Hollingworth P et al. “Common variants at ABCA7, MS4A6A/MS4A4E, EPHA1, CD33 and CD2AP are associated with Alzheimer's disease.” Nature Genetics (2011)

Allele C

OR 1.17

p 3.0e-14

N 59,715

Large GWAS

European

“A genome-wide association meta-analysis of all-cause and vascular dementia.” Alzheimer's & Dementia : the Journal of the Alzheimer's Association 20(9):5973-5995 (2024)

Allele C

OR —

β -0.139

p 2.0e-17

N 523,452

Meta-analysisLarge GWAS

multi-ancestry

Zhu R et al. “The Bridging Integrator 1 Gene Polymorphism rs744373 and the Risk of Alzheimer's Disease in Caucasian and Asian Populations: An Updated Meta-Analysis.” Molecular Neurobiology (2017)

Allele C

OR 1.10

p 1.0e-2

N 29,965

Meta-analysis

multi-ancestry

Hu X et al. “Meta-analysis for genome-wide association study identifies multiple variants at the BIN1 locus associated with late-onset Alzheimer's disease.” Plos One (2011)

Allele C

OR 1.19

p 1.0e-10

N 16,881

Meta-analysisLarge GWAS

European

Abdul Aziz M et al. “Link of BIN1, CLU, and IDE Gene Polymorphisms with the Susceptibility of Alzheimer's Disease: Evidence from a Meta-analysis.” Current Alzheimer Research (2022)

Allele C

OR —

p —

Meta-analysis

multi-ancestry

Cerebrospinal fluid phosphorylated tau levels

The G allele of rs744373 is associated with higher cerebrospinal fluid phosphorylated tau (p-tau), an established biomarker of Alzheimer's disease-related neurodegeneration. A 2022 genome-wide meta-analysis of CSF AD biomarkers across multiple European cohorts (7,798 discovery plus 4,755 replication individuals) identified this association at p=8×10⁻¹⁰ (beta z-score = 6.15). This finding provides a plausible biological pathway linking the BIN1 locus to tau pathology, complementing the epidemiological AD risk association.

Jansen IE et al. “Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.” Acta Neuropathologica 144(5):821-842 (2022)

Allele G

OR —

β 6.150

p 8.0e-10

N 12,553

Meta-analysisLarge GWAS

European

▶

GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

dementia

“A genome-wide association meta-analysis of all-cause and vascular dementia.” Alzheimer's & Dementia : the Journal of the Alzheimer's Association 20(9):5973-5995 (2024)

Allele A

OR 0.14

p 2.0e-17

N 524,852

Meta-analysisLarge GWAS

multi-ancestry

p-tau measurement

Jansen IE et al. “Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.” Acta Neuropathologica 144(5):821-842 (2022)

Allele G

OR 6.15

p 8.0e-10

N 7,798

Meta-analysis

European

▶

Research that mentions this SNP (2)

▶

A Comprehensive Genetic Association Study of Alzheimer Disease in African Americans

AssociationN=1,009Logue MW et al.(2011)· Archives of Neurology

This comprehensive genome-wide association study examined genetic variants contributing to late-onset Alzheimer's disease (AD) in 513 African American cases and 496 controls, plus replication in 5 white cohorts. The APOE ε4 allele showed strong association (P=9.69×10⁻²³), and after adjusting for APOE, rs6859 in PVRL2 remained significantly associated (P=0.0087). The study found associations with variants in CLU, PICALM, BIN1, EPHA1, MS4A, ABCA7, and CD33, though effect directions sometimes differed from white populations. Novel associations with suggestive evidence were identified in PROX1, CNTNAP2, STK24, and other genes, though not replicated in whites.

Traits studied:Alzheimer diseaseLate-onset Alzheimer disease (LOAD)

PubMed DOI Metascience Observatory

▶

Genome-wide Analysis of Genetic Loci Associated With Alzheimer Disease

AssociationN=35,000Seshadri S. et al.(2010)· JAMA

This 3-stage genome-wide association meta-analysis study identified 5 novel and confirmed loci associated with late-onset Alzheimer's disease across over 35,000 individuals. The study discovered two new genome-wide significant loci: rs744373 in BIN1 (OR 1.13, p=1.59×10⁻¹¹) and rs597668 near EXOC3L2 (OR 1.18, p=6.45×10⁻⁹), and confirmed three previously reported loci in APOE (OR 2.53, p=1.04×10⁻²⁹⁵), CLU (OR 0.85, p=1.62×10⁻¹⁶), and PICALM (OR 0.89, p=3.16×10⁻¹²). These findings were validated in an independent Spanish replication sample of 2,349 individuals.

rs744373

Key Literature Trait Associations

Alzheimer's Disease

Cerebrospinal fluid phosphorylated tau levels

GWAS Catalog Trait Associations (2)

dementia

p-tau measurement

Research that mentions this SNP (2)

Community Wiki

Comments