Abstract 154: Heritability of Ischemic White Matter Lesions in a Family Population with Increased Susceptibility of Vascular Disease
Introduction: Ischemic strokes are more likely to occur in the subcortical region of the brain, and also cluster strongly in families. However, the extent to which ischemic white matter lesions (WML) are heritable in a high risk healthy population remains unknown. We thus examined the heritability of ischemic WML volumes in both the periventricular (PV) and subcortical (SC) brain regions in apparently healthy European American (EA) and African American (AA) families with increased susceptibility for vascular disease .
Methods: We measured traditional risk factors, and imaged the brains of 579 healthy first degree relatives of probands with early onset CAD prior to 60 years of age. PV and SC WML volumes were directly measured using 3T cranial MRI. The location and volume of lesions were characterized using standard automated software. Maximum-likelihood estimates of polygenic heritability were performed on the unadjusted and adjusted transformed WML traits with the use of variance components models in the ASSOC subroutine of SAGE.
Results: Heritability was analyzed in 359 EA from 122 pedigrees as well as in 220 AA from 75 pedigrees. Participants were 58% women, 37% AA; mean age 51.5±11 (range of 29-74 years). Adjusting for age, sex, systolic blood pressure, and intracranial volume we determined the heritability for total WML volumes in EA’s (h2=0.62, SE 0.135, p<0.00001), and AA (h2=0.16, SE 0.24, p=0.25); for PV WML in EA’s (h2=0.31, SE 0.145, p=0.00167) in AA’s (h2=0.037, SE 0.165, p=0.4118); and for SC WML in EA’s (h2=0.581, SE 0.166, p=0.0002) and AA’s (h2=0.582, SE 0.182, p=0.0007).
Conclusions: Total WML volumes were highly heritable in EA, as were both PV, and SC WML volumes. In AA, only SC WML volumes were significantly heritable. In general, heritability estimates where greater for the SC than for the PV WML volumes. These findings suggest a heritable precursor state of stroke-related small vessel cerebrovascular disease in EA, generally greater for the subcortical region where subsequent strokes are more likely to occur, and a similar state only in the SC region in AA high risk healthy family members with susceptibility to vascular disease.
- Risk factors
- Magnetic resonance imaging
- Cerebrovascular disorders
- Vascular cognitive impairment
- Subclinical atherosclerosis
Author Disclosures: P.A. Nyquist: None. L.R. Yanek: None. L.C. Becker: None. B.G. Kral: None. D. Vaidya: None. D.M. Becker: None.
- © 2015 by American Heart Association, Inc.