rs4888378

mixedMag 4.0

This is a intron variant variant in the CFDP1 gene.

Key Literature Trait Associations

Coronary artery disease

The A allele at rs4888378 is associated with reduced risk of coronary artery disease (CAD) in one of the largest CAD GWAS meta-analyses to date. Van der Harst and Verweij (2018) combined CARDIoGRAMplusC4D (88,192 cases / 162,544 controls) with UK Biobank (34,541 cases / 261,984 controls), totalling over 586,000 participants, and identified rs4888378 as one of 64 novel CAD loci (beta=−0.044 per A allele, p=6×10⁻¹⁵). This builds on the original IMPROVE study (Gertow et al., 2012) which reported OR=0.83 for the A allele versus G allele in CAD case-control analyses. The CFDP1/BCAR1 locus thus shows concordant cardioprotective effects across both subclinical (cIMT) and clinical (CAD) endpoints.

van der Harst P et al. “Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease.” Circulation Research 122(3):433-443 (2018)

Allele A

OR —

β -0.044 ±0.006

p 6.0e-15

N 586,261

Large GWAS

European

Gertow K et al. “Identification of the BCAR1-CFDP1-TMEM170A locus as a determinant of carotid intima-media thickness and coronary artery disease risk.” Circulation. Cardiovascular Genetics 5(6):656-665 (2012)

Allele A

OR 0.83

p 6.5e-6

N 95,888

Small GWAS

European

Carotid Intima-Media Thickness

The A allele at rs4888378, intronic in CFDP1 at the BCAR1-CFDP1-TMEM170A locus, is associated with reduced carotid intima-media thickness (cIMT), a subclinical measure of atherosclerosis. Discovered in the IMPROVE study (N=3,430) and replicated across 5 European cohorts (N=11,590). Functional assays show the A allele reduces enhancer activity by 35-92%, with eQTL analyses implicating lower BCAR1 expression in vascular tissue.

Allele G

OR —

β -0.005

p 6.7e-7

Preliminary work

Boardman-Pretty F et al. “Functional Analysis of a Carotid Intima-Media Thickness Locus Implicates BCAR1 and Suggests a Causal Variant.” Circulation. Cardiovascular Genetics (2015)

Allele G

OR —

β -0.005

p 1.6e-4

N 8,000

Preliminary work

European

Hemerich D et al. “Impact of carotid atherosclerosis loci on cardiovascular events.” Atherosclerosis (2015)

Allele G

OR —

p —

Candidate gene study

European

Migraine

The G allele of rs4888378 is associated with increased migraine risk in a large multiethnic GWAS meta-analysis. Choquet et al. (2021) combined the GERA cohort and UK Biobank (85,726 cases / 803,292 controls) and identified rs4888378 among 79 migraine-associated loci, including 45 novel ones (p=4×10⁻¹³, OR≈1.04 per G allele). The biological link between the CFDP1/BCAR1 locus and migraine susceptibility is not yet established but the variant's chromosome 16q23.1 location and its gene regulatory effects may implicate vascular or neurological mechanisms shared across vascular and migraine phenotypes.

Choquet H et al. “New and sex-specific migraine susceptibility loci identified from a multiethnic genome-wide meta-analysis.” Communications Biology 4(1):864 (2021)

Allele G

OR 0.96

p 4.0e-13

N 889,018

Meta-analysisLarge GWAS

multi-ancestry

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