Perminder S Sachdev1, Anbupalam Thalamuthu2, Karen A Mather2, David Ames2, Margaret J Wright2, Wei Wen2. 1. 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. 2. 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.
Abstract
BACKGROUND AND PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND AND PURPOSE: 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. METHODS: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. RESULTS: 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. CONCLUSIONS: 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.
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Authors: Nicola J Armstrong; Karen A Mather; Muralidharan Sargurupremraj; Maria J Knol; Rainer Malik; Claudia L Satizabal; Lisa R Yanek; Wei Wen; Vilmundur G Gudnason; Nicole D Dueker; Lloyd T Elliott; Edith Hofer; Joshua Bis; Neda Jahanshad; Shuo Li; Mark A Logue; Michelle Luciano; Markus Scholz; Albert V Smith; Stella Trompet; Dina Vojinovic; Rui Xia; Fidel Alfaro-Almagro; David Ames; Najaf Amin; Philippe Amouyel; Alexa S Beiser; Henry Brodaty; Ian J Deary; Christine Fennema-Notestine; Piyush G Gampawar; Rebecca Gottesman; Ludovica Griffanti; Clifford R Jack; Mark Jenkinson; Jiyang Jiang; Brian G Kral; John B Kwok; Leonie Lampe; David C M Liewald; Pauline Maillard; Jonathan Marchini; Mark E Bastin; Bernard Mazoyer; Lukas Pirpamer; José Rafael Romero; Gennady V Roshchupkin; Peter R Schofield; Matthias L Schroeter; David J Stott; Anbupalam Thalamuthu; Julian Trollor; Christophe Tzourio; Jeroen van der Grond; Meike W Vernooij; Veronica A Witte; Margaret J Wright; Qiong Yang; Zoe Morris; Siggi Siggurdsson; Bruce Psaty; Arno Villringer; Helena Schmidt; Asta K Haberg; Cornelia M van Duijn; J Wouter Jukema; Martin Dichgans; Ralph L Sacco; Clinton B Wright; William S Kremen; Lewis C Becker; Paul M Thompson; Thomas H Mosley; Joanna M Wardlaw; M Arfan Ikram; Hieab H H Adams; Sudha Seshadri; Perminder S Sachdev; Stephen M Smith; Lenore Launer; William Longstreth; Charles DeCarli; Reinhold Schmidt; Myriam Fornage; Stephanie Debette; Paul A Nyquist Journal: Stroke Date: 2020-06-10 Impact factor: 7.914
Authors: Farah Ammous; Wei Zhao; Scott M Ratliff; Minjung Kho; Lulu Shang; Alana C Jones; Ninad S Chaudhary; Hemant K Tiwari; Marguerite R Irvin; Donna K Arnett; Thomas H Mosley; Lawrence F Bielak; Sharon L R Kardia; Xiang Zhou; Jennifer Smith Journal: Epigenetics Date: 2020-10-26 Impact factor: 4.528