期刊
NEUROBIOLOGY OF AGING
卷 36, 期 3, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2014.11.008
关键词
Magnetic resonance imaging; Type 2 diabetes; Genetics; Heritability
资金
- National Institutes of Health [R01 HL67348, R01 HL092301, R01 NS058700, R01 NS075107, F32 DK083214-01, F31 AG044879]
- General Clinical Research Centre of the Wake Forest School of Medicine [M01 RR07122, F32 HL085989]
Patients with type 2 diabetes are at increased risk of age-related cognitive decline and dementia. Neuroimaging measures such as white matter lesion volume, brain volume, and fractional anisotropy may reflect the pathogenesis of these cognitive declines, and genetic factors may contribute to variability in these measures. This study examined multiple neuroimaging measures in 465 participants from 238 families with extensive genotype data in the type 2 diabetes enriched Diabetes Heart Study-Mind cohort. Heritability of these phenotypes and their association with candidate single-nucleotide polymorphisms (SNPs), and SNP data from genome-and exome-wide arrays were explored. All neuroimaging measures analyzed were significantly heritable ((h) over cap (2) = 0.55-0.99 in unadjusted models). Seventeen candidate SNPs (from 16 genes/regions) associated with neuroimaging phenotypes in prior studies showed no significant evidence of association. A missense variant (rs150706952, A432V) in PLEKHG4B from the exome-wide array was significantly associated with white matter mean diffusivity (p = 3.66 x 10(-7)) and gray matter mean diffusivity (p = 2.14 x 10(-7)). This analysis suggests genetic factors contribute to variation in neuroimaging measures in a population enriched for metabolic disease and other associated comorbidities. (C) 2015 Elsevier Inc. All rights reserved.
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