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Age differences in periventricular and deep white matter lesions.

ABSTRACT: Deep white matter hyperintensity (DWMH) and periventricular (PV) white matter lesion volumes are associated with age and subsequent stroke. We studied age differences in these volumes accounting for collinearity and risk factors. Subjects were 563 healthy family members of early-onset coronary artery disease patients. Using 3T magnetic resonance imaging, lesions were classified as DWMH or PV. Age association with lesion classification was analyzed using random effects Tobit regression, adjusting for intracranial volume (ICV) and risk factors. Subjects were 60% women, 36% African-American, mean age 51 ± 11 years. In multivariable analysis adjusted for PV and ICV, DWMH was associated with age (p < 0.001) and female sex (p = 0.003). PV, adjusted for DWMH and ICV, was age associated (p < 0.001). For each age decade, DWMH showed 0.07 log units/decade greater volume (95% CI = 0.04-0.11); PV was 0.18 log units/decade greater (95% CI = 0.14-0.23); slope differences (p < 0.001). In people with a family history of coronary artery disease, PV and DWMH are independently and differentially associated with age controlling for traditional risk factors.

SUBMITTER: Nyquist PA

PROVIDER: S-EPMC4380525 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Age differences in periventricular and deep white matter lesions.

Nyquist Paul A PA Bilgel Murat M Gottesman Rebecca R Yanek Lisa R LR Moy Taryn F TF Becker Lewis C LC Cuzzocreo Jennifer L JL Prince Jerry J Wasserman Bruce A BA Yousem David M DM Becker Diane M DM Kral Brian G BG Vaidya Dhananjay D

Neurobiology of aging 20150107 4

Deep white matter hyperintensity (DWMH) and periventricular (PV) white matter lesion volumes are associated with age and subsequent stroke. We studied age differences in these volumes accounting for collinearity and risk factors. Subjects were 563 healthy family members of early-onset coronary artery disease patients. Using 3T magnetic resonance imaging, lesions were classified as DWMH or PV. Age association with lesion classification was analyzed using random effects Tobit regression, adjusting ...[more]

PMID: 25659858

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Project description:Background and purposePeriventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings.MethodsParticipants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC.ResultsIn the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 (NBEAL), 10q23.1 (TSPAN14/FAM231A), and 10q24.33 (SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 (NOS3) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype.ConclusionsOur study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.

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Age differences in periventricular and deep white matter lesions.

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Age differences in periventricular and deep white matter lesions.

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