Results of a multiethnic, genomewide association study meta-analysis suggest that that high blood pressure (BP) may be a predictive modifiable causal risk factor for magnetic resonance imaging (MRI)-defined brain infarcts (BIs). In addition, the study found genetic risk loci for BI. The findings from this study were published in Neurology.
The genomewide association study meta-analysis was performed using 18 prospective population-based cohorts (N=20,949) of 5 ethnicities from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Associations between MRI-defined BIs (n=3726) and small subcortical brain infarcts (SSBIs; n=2021) with vascular risk factors and their genetic risk scores were assessed. Top loci from a total of 7 population-based cohorts (n=6862) including 1483 individuals with BIs and 630 individuals with SBBIs were followed, and associations between related phenotypes (ie, ischemic stroke and pathologically defined BIs) were tested.
The mean prevalence for BIs (17.7%) and SSBIs (10.5%) rose sharply after patients reached age 65 years. The 2 loci that showed genomewide significant association with BIs included FBN2 (P =1.77×10−8) and LINC00539/ZDHHC20 (P =5.82×10−9), both of which demonstrated associations with BP-related phenotypes. Both FBN2 and LINC00539/ZDHHC20, however, did not show an association with BP-related phenotypes in a smaller follow-up sample.
In adjusted analyses, associations between BIs and SSBIs were found for BP traits (BI, P =9.38×10−25; SSBI, P =5.23×10−14), smoking (BI, P =4.4×10−10; SSBI, P =1.2×10−4), diabetes (BI, P =1.7×10−8; SSBI, P =2.8×10−3), previous cardiovascular disease (BI, P =1.0×10−18; SSBI, P =2.3×10−7), stroke (BI, P =3.9×10−69; SSBI, P =3.2×10−24), and MRI-defined white matter hyperintensity burden (BI, P =1.43×10−157; SSBI, P =3.16×10−106).
According to the investigators, the heterogeneity in BI and SSBI etiology limited their ability to discover robust genetic risk variants.
“Our findings provide definitive evidence for a major and predominant association of increasing BP levels with increased risk of BI and SSBI,” the researchers wrote. “The observational evidence is overwhelming for a strong causal relation between high BP and risk of BI and SSBI.”
Chauhan G, Adams HHH, Satizabal CL, et al; Stroke Genetics Network (SiGN), the International Stroke Genetics Consortium (ISGC), METASTROKE, Alzheimer’s Disease Genetics Consortium (ADGC), and the Neurology Working Group of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Genetic and lifestyle risk factors for MRI-defined brain infarcts in a population-based setting [published online January 16, 2019]. Neurology. doi: 10.1212/WNL.0000000000006851