Neurological

Genetic variants associated with lacunar stroke and white matter hyperintensity

According to study results published in The Lancet Neurology, a dozen loci have been linked to lacunar stroke during a pooled genome-wide association study (GWAS).

The study researchers performed a meta-analysis of GWAS using data from magnetic resonance imaging (MRI) -confirmed lacunar stroke (cases: n = 2987; control group participants: n = 29,540) and TOAST-phenotyped lacunar stroke (cases: n = 4351; control) Group participants: n = 225,258. GWAS data of white matter hyperintensity volumes (n = 42,310) were used to perform multitrait analysis. The data were obtained from European, North American and Australian populations.

When the linkage imbalance was corrected, the heritability for MRI-confirmed and non-MRI-confirmed lacunar stroke was 0.065 (standard error [SE], 0.017) and 0.0081 (SE, 0.0025), respectively. The genetic correlation between MRI and non-MRI confirmed stroke was 0.61 (SE, 0.21; P = 0.0033).

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A total of 5 loci were associated with lacunar stroke, 4 of which were new (ULK4, ZCCHC14, ZBTB14-EPB41L3, SPI1-SLC39A13-PSMC3-RAPSN) and one previously associated with intracerebral hemorrhage and lacunar stroke ( ICA1L-WDR12-CARF – NBEAL1).

The genetic correlation with lacunar strokes and white matter hyperintensities, which are responsible for the linkage imbalance, was 0.46 (SE, 0.10; P = 4.6´10-6) and 0 between the MRI-confirmed and pooled cohorts .37 (SE, 0.09; P = 4.0 ‘.). 10-5) or

The joint analysis identified 3 new loci (COL4A2, SH3PXD2A, LOX-ZNF474I-LOC100505841, SLC25A44-PMF1-BGLAP) and 4 loci previously associated with white matter hyperintensities (FOXF2-FOXQ1, VTA1-G GPR126, HTRA1-ARMS2 ).

These 12 loci accounted for 1.4% of the total heritability of lacunar stroke.

A pathway analysis of these loci identified the phosphatidyl-inositol-5-phosphate bond (P = 2.2´10-6), the structural component of the extracellular matrix (P = 6.2´10-6), the extracellular matrix component, the Lends elasticity (P = 8.9´10-6), middle ear morphogenesis (P = 2.3´10-5) and carousel binding (P = 2.7´10-5).

Eleven of the 12 loci were categorized as potential treatment goals.

Lacunar stroke was positively associated with systolic blood pressure (odds ratio [OR], 1.04; P = 3.1’10-6), diastolic blood pressure (OR, 1.06; P = 3.1’10-5), type 2 diabetes (OR, 1.10; P =, 00019) and pulse pressure (OR, 1.04; P = 0.0025).

These results may not be generalizable because the genetic samples are from a non-diverse population.

In this pooled GWAS, 12 loci were associated with lacunar stroke. Additional studies are needed to validate these relationships and assess whether they may represent therapeutic goals.

Disclosure: Some authors stated links with pharmaceutical, biotech, and / or device manufacturers. For a full list of the details, see the original article.

reference

Traylor M., Persyn E., Tomppo L, et al. Genetic basis of lacunar stroke: a pooled analysis of individual patient data and genome-wide association studies. Lancet Neurol. 2021; 20 (5): 351-361. doi: 10.1016 / S1474-4422 (21) 00031-4

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