title: White Matter Hyperintensities Are Under Strong Genetic Influence.
abstract: The genetic basis of white matter hyperintensities (WMH) is still unknown. This study examines the heritability of WMH in both sexes and in different brain regions, and the influence of age.
  
  
  
  Participants from the Older Australian Twins Study were recruited (n=320; 92 monozygotic and 68 dizygotic pairs) who volunteered for magnetic resonance imaging scans and medical assessments. Heritability, that is, the ratio of the additive genetic variance to the total phenotypic variance, was estimated using the twin design.
  
  
  
  Heritability was high for total WMH volume (0.76), and for periventricular WMH (0.64) and deep WMH (0.77), and varied from 0.18 for the cerebellum to 0.76 for the occipital lobe. The genetic correlation between deep and periventricular WMH regions was 0.85, with one additive genetics factor accounting for most of the shared variance. Heritability was consistently higher in women in the cerebral regions. Heritability in deep but not periventricular WMH declined with age, in particular after the age of 75.
  
  
  
  WMH have a strong genetic influence but this is not uniform through the brain, being higher for deep than periventricular WMH and in the cerebral regions. The genetic influence is higher in women, and there is an age-related decline, most markedly for deep WMH. The data suggest some heterogeneity in the pathogenesis of WMH for different brain regions and for men and women.
authors.affiliation: From the Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, The University of New South Wales, Australia (P.S.S., A.T., K.A.M., W.W.); Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia (P.S.S., W.W.); National Ageing Research Institute, University of Melbourne, Parkville, Victoria, Australia (D.A.); NeuroImaging Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia (M.J.W.); and Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia (M.J.W.).New South WalesNew South WalesNew South WalesNew South WalesNew South WalesNew South WalesQueenslandQueenslandVictoria p.sachdev@unsw.edu.au.
authors.forename: Perminder S
authors.initials: PS
authors.lastname: Sachdev
authors.affiliation: From the Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, The University of New South Wales, Australia (P.S.S., A.T., K.A.M., W.W.); Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia (P.S.S., W.W.); National Ageing Research Institute, University of Melbourne, Parkville, Victoria, Australia (D.A.); NeuroImaging Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia (M.J.W.); and Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia (M.J.W.).New South WalesNew South WalesNew South WalesNew South WalesNew South WalesNew South WalesQueenslandQueenslandVictoria.
authors.forename: Anbupalam
authors.initials: A
authors.lastname: Thalamuthu
authors.affiliation: From the Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, The University of New South Wales, Australia (P.S.S., A.T., K.A.M., W.W.); Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia (P.S.S., W.W.); National Ageing Research Institute, University of Melbourne, Parkville, Victoria, Australia (D.A.); NeuroImaging Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia (M.J.W.); and Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia (M.J.W.).New South WalesNew South WalesNew South WalesNew South WalesNew South WalesNew South WalesQueenslandQueenslandVictoria.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Mather
authors.affiliation: From the Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, The University of New South Wales, Australia (P.S.S., A.T., K.A.M., W.W.); Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia (P.S.S., W.W.); National Ageing Research Institute, University of Melbourne, Parkville, Victoria, Australia (D.A.); NeuroImaging Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia (M.J.W.); and Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia (M.J.W.).New South WalesNew South WalesNew South WalesNew South WalesNew South WalesNew South WalesQueenslandQueenslandVictoria.
authors.forename: David
authors.initials: D
authors.lastname: Ames
authors.affiliation: From the Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, The University of New South Wales, Australia (P.S.S., A.T., K.A.M., W.W.); Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia (P.S.S., W.W.); National Ageing Research Institute, University of Melbourne, Parkville, Victoria, Australia (D.A.); NeuroImaging Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia (M.J.W.); and Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia (M.J.W.).New South WalesNew South WalesNew South WalesNew South WalesNew South WalesNew South WalesQueenslandQueenslandVictoria.
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Wright
authors.affiliation: From the Centre for Healthy Brain Ageing (CHeBA), School of Psychiatry, UNSW Medicine, The University of New South Wales, Australia (P.S.S., A.T., K.A.M., W.W.); Neuropsychiatric Institute, Prince of Wales Hospital, Randwick, New South Wales, Australia (P.S.S., W.W.); National Ageing Research Institute, University of Melbourne, Parkville, Victoria, Australia (D.A.); NeuroImaging Genetics Laboratory, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia (M.J.W.); and Queensland Brain Institute, The University of Queensland, Brisbane, QLD, Australia (M.J.W.).New South WalesNew South WalesNew South WalesNew South WalesNew South WalesNew South WalesQueenslandQueenslandVictoria.
authors.forename: Wei
authors.initials: W
authors.lastname: Wen
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology; D001315:Australia / Q000453:epidemiology; D001927:Brain Diseases / Q000000981:diagnostic imaging* / Q000453:epidemiology*; D002531:Cerebellum / Q000000981:diagnostic imaging; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009778:Occipital Lobe / Q000000981:diagnostic imaging; D012727:Sex Characteristics; D066127:White Matter / Q000000981:diagnostic imaging*
keywords: aging; epidemiology; heritable quantitative trait; magnetic resonance imaging; white matter