title: White matter disease in midlife is heritable, related to hypertension, and shares some genetic influence with systolic blood pressure.
abstract: White matter disease in the brain increases with age and cardiovascular disease, emerging in midlife, and these associations may be influenced by both genetic and environmental factors. We examined the frequency, distribution, and heritability of abnormal white matter and its association with hypertension in 395 middle-aged male twins (61.9 ± 2.6 years) from the Vietnam Era Twin Study of Aging, 67% of whom were hypertensive. A multi-channel segmentation approach estimated abnormal regions within the white matter. Using multivariable regression models, we characterized the frequency distribution of abnormal white matter in midlife and investigated associations with hypertension andApolipoprotein E-ε4 status and the impact of duration and control of hypertension. Then, using the classical twin design, we estimated abnormal white matter heritability and the extent of shared genetic overlap with blood pressure. Abnormal white matter was predominantly located in periventricular and deep parietal and frontal regions; associated with age (t= 1.9,p= 0.05) and hypertension (t= 2.9,p= 0.004), but notApolipoproteinε4 status; and was greater in those with uncontrolled hypertension relative to controlled (t= 3.0,p= 0.003) and normotensive (t= 4.0,p= 0.0001) groups, suggesting that abnormal white matter may reflect currently active cerebrovascular effects. Abnormal white matter was highly heritable (a2= 0.81) and shared some genetic influences with systolic blood pressure (rA= 0.26), although there was evidence for distinct genetic contributions and unique environmental influences. Future longitudinal research will shed light on factors impacting white matter disease presentation, progression, and potential recovery.
authors: Department of Psychiatry at the University of California, San Diego, La Jolla, CA, USA; Department of Radiology at the University of California, San Diego, La Jolla, CA, USA.
authors: Christine
authors: C
authors: Fennema-Notestine
authors: Department of Radiology at the University of California, San Diego, La Jolla, CA, USA.
authors: Linda K
authors: LK
authors: McEvoy
authors: Department of Psychiatry at the University of California, San Diego, La Jolla, CA, USA.
authors: Randy
authors: R
authors: Notestine
authors: Department of Psychiatry at the University of California, San Diego, La Jolla, CA, USA.
authors: Matthew S
authors: MS
authors: Panizzon
authors: School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.
authors: Wai-Ying Wendy
authors: WW
authors: Yau
authors: Department of Psychiatry at the University of California, San Diego, La Jolla, CA, USA.
authors: Carol E
authors: CE
authors: Franz
authors: Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
authors: Michael J
authors: MJ
authors: Lyons
authors: Department of Psychiatry at the University of California, San Diego, La Jolla, CA, USA.
authors: Lisa T
authors: LT
authors: Eyler
authors: Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
authors: Michael C
authors: MC
authors: Neale
authors: Department of Biostatistics, St. Louis University and St. Louis Veterans Affairs Medical Center, St. Louis, MO, USA.
authors: Hong
authors: H
authors: Xian
authors: Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
authors: Ruth E
authors: RE
authors: McKenzie
authors: Department of Psychiatry at the University of California, San Diego, La Jolla, CA, USA; Center of Excellence for Stress and Mental Health, VA San Diego Healthcare System, San Diego, CA, USA.
authors: William S
authors: WS
authors: Kremen
mesh_terms: D000368:Aged; D001794:Blood Pressure / Q000235:genetics*; D015897:Comorbidity; D006801:Humans; D006973:Hypertension / Q000453:epidemiology*; D056784:Leukoencephalopathies / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged
keywords: AWM, abnormal white matter; ApoE, apolipoprotein E; BMI, body mass index; Blood pressure; Brain; CRP, C-Reactive protein; DBP, diastolic blood pressure; HDL, high-density lipoprotein; HTN, hypertension; Heritability; Hypertension; ICV, intracranial vault; LDL, Low; MRI; SBP, systolic blood pressure; White matter