Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.,Nature Communications

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Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults.
Nature Communications ( IF 14.7 ) Pub Date : 2020-09-22 , DOI: 10.1038/s41467-020-18367-y
Edith Hofer _{1,

2} , Gennady V Roshchupkin _{3,

4,

5} , Hieab H H Adams _{3,

5} , Maria J Knol ₅ , Honghuang Lin ₆ , Shuo Li ₇ , Habil Zare _{8,

9} , Shahzad Ahmad ₅ , Nicola J Armstrong ₁₀ , Claudia L Satizabal _{8,

11} , Manon Bernard ₁₂ , Joshua C Bis ₁₃ , Nathan A Gillespie _{14,

15} , Michelle Luciano _{16,

17} , Aniket Mishra ₁₈ , Markus Scholz _{19,

20} , Alexander Teumer ₂₁ , Rui Xia ₂₂ , Xueqiu Jian ₂₂ , Thomas H Mosley ₂₃ , Yasaman Saba ₂₄ , Lukas Pirpamer ₁ , Stephan Seiler _{25,

26} , James T Becker ₂₇ , Owen Carmichael ₂₈ , Jerome I Rotter ₂₉ , Bruce M Psaty ₁₃ , Oscar L Lopez ₂₇ , Najaf Amin ₅ , Sven J van der Lee ₅ , Qiong Yang ₇ , Jayandra J Himali ₇ , Pauline Maillard _{25,

26} , Alexa S Beiser _{7,

11} , Charles DeCarli _{25,

26} , Sherif Karama ₃₀ , Lindsay Lewis ₃₀ , Mat Harris _{16,

31,

32,

33} , Mark E Bastin _{16,

31,

32,

33} , Ian J Deary _{16,

17} , A Veronica Witte _{34,

35} , Frauke Beyer _{34,

35} , Markus Loeffler _{19,

20} , Karen A Mather _{36,

37} , Peter R Schofield _{37,

38} , Anbupalam Thalamuthu ₃₆ , John B Kwok _{38,

39} , Margaret J Wright _{40,

41} , David Ames _{42,

43} , Julian Trollor _{36,

44} , Jiyang Jiang ₃₆ , Henry Brodaty _{36,

45} , Wei Wen ₃₆ , Meike W Vernooij _{3,

5} , Albert Hofman _{5,

46} , André G Uitterlinden ₅ , Wiro J Niessen _{3,

47} , Katharina Wittfeld _{48,

49} , Robin Bülow ₅₀ , Uwe Völker ₅₁ , Zdenka Pausova _{12,

52} , G Bruce Pike ₅₃ , Sophie Maingault ₅₄ , Fabrice Crivello ₅₄ , Christophe Tzourio _{18,

55} , Philippe Amouyel _{56,

57,

58} , Bernard Mazoyer ₅₄ , Michael C Neale ₁₄ , Carol E Franz ₅₉ , Michael J Lyons ₆₀ , Matthew S Panizzon ₅₉ , Ole A Andreassen ₆₁ , Anders M Dale ₆₂ , Mark Logue _{7,

63,

64} , Katrina L Grasby ₆₅ , Neda Jahanshad ₆₆ , Jodie N Painter ₆₅ , Lucía Colodro-Conde ₆₅ , Janita Bralten _{67,

68} , Derrek P Hibar _{66,

69} , Penelope A Lind ₆₅ , Fabrizio Pizzagalli ₆₆ , Jason L Stein ₇₀ , Paul M Thompson ₆₆ , Sarah E Medland ₆₅ , , Perminder S Sachdev _{36,

71} , William S Kremen ₅₉ , Joanna M Wardlaw _{16,

31,

32,

33} , Arno Villringer _{34,

72} , Cornelia M van Duijn _{5,

73} , Hans J Grabe _{48,

49} , William T Longstreth ₇₄ , Myriam Fornage ₂₂ , Tomas Paus _{75,

76} , Stephanie Debette _{11,

18,

77} , M Arfan Ikram _{3,

5,

78} , Helena Schmidt ₂₄ , Reinhold Schmidt ₁ , Sudha Seshadri _{8,

11}

Affiliation

Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Graz, Austria.
Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Graz, Austria.
Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, The Netherlands.
Department of Medical Informatics, Erasmus MC, Rotterdam, The Netherlands.
Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
Section of Computational Biomedicine, Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, UT Health San Antonio, San Antonio, USA.
Department of Cell Systems & Anatomy, The University of Texas Health Science Center, San Antonio, TX, USA.
Mathematics and Statistics, Murdoch University, Perth, Australia.
Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
Hospital for Sick Children, Toronto, ON, Canada.
Cardiovascular Health Research Unit, Department of Medicine, Epidemiology and Health Services, University of Washington, Seattle, WA, USA.
Virginia Institute for Psychiatric and Behavior Genetics, Virginia Commonwealth University, Richmond, VA, USA.
QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Centre for Cognitive Epidemiology and Cognitive Ageing, University of Edinburgh, Edinburgh, UK.
Department of Psychology, University of Edinburgh, Edinburgh, UK.
University of Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219, Bordeaux, France.
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
LIFE Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany.
Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany.
Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Graz, Austria.
Imaging of Dementia and Aging (IDeA) Laboratory, Department of Neurology, University of California-Davis, Davis, CA, USA.
Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento, CA, USA.
Departments of Psychiatry, Neurology, and Psychology, University of Pittsburgh, Pittsburgh, PA, USA.
Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute and Pediatrics at Harbor-UCLA Medical Center, Torrance, CA, USA.
McGill University, Montreal Neurological Institute, Montreal, QC, Canada.
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK.
Brain Research Imaging Centre, University of Edinburgh, Edinburgh, UK.
Scottish Imaging Network, A Platform for Scientific Excellence (SINAPSE) Collaboration, Department of Neuroimaging Sciences, The University of Edinburgh, Edinburgh, UK.
Department of Neurology, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Faculty of Medicine, CRC 1052 Obesity Mechanisms, University of Leipzig, Leipzig, Germany.
Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Sydney, Australia.
Neuroscience Research Australia, Sydney, Australia.
School of Medical Sciences, University of New South Wales, Sydney, Australia.
Brain and Mind Centre - The University of Sydney, Camperdown, NSW, Australia.
Queensland Brain Institute, The University of Queensland, St Lucia, QLD, Australia.
Centre for Advanced Imaging, The University of Queensland, St Lucia, QLD, Australia.
National Ageing Research Institute, Royal Melbourne Hospital, Parkvill, VIC, Australia.
Academic Unit for Psychiatry of Old Age, University of Melbourne, St George's Hospital, Kew, VIC, Australia.
Department of Developmental Disability Neuropsychiatry, School of Psychiatry, University of New South Wales, Sydney, NSW, Australia.
Dementia Centre for Research Collaboration, University of New South Wales, Sydney, NSW, Australia.
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
Imaging Physics, Faculty of Applied Sciences, Delft University of Technology, Delft, The Netherlands.
German Center for Neurodegenerative Diseases (DZNE), Site Rostock/Greifswald, Greifswald, Germany.
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Greifswald, Germany.
Institute for Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany.
Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
Departments of Physiology and Nutritional Sciences, University of Toronto, Toronto, ON, Canada.
Departments of Radiology and Clinial Neurosciences, University of Calgary, Calgary, AB, Canada.
Institut des Maladies Neurodégénratives UMR5293, CEA, CNRS, University of Bordeaux, Bordeaux, France.
Pole de santé publique, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.
Centre Hospitalier Universitaire de Bordeaux, France; Inserm U1167, Lille, France.
Department of Epidemiology and Public Health, Pasteur Institute of Lille, Lille, France.
Department of Public Health, Lille University Hospital, Lille, France.
Department of Psychiatry, University of California San Diego, San Diego, CA, USA.
Department of Psychological and Brain Sciences, Boston University, Boston, MA, USA.
NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo and Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
Departments of Radiology and Neurosciences, University of California, San Diego, La Jolla, CA, USA.
National Center for PTSD at Boston VA Healthcare System, Boston, MA, USA.
Department of Psychiatry and Department of Medicine-Biomedical Genetics Section, Boston University School of Medicine, Boston, MA, USA.
Psychiatric Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Imaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Department of Human Genetics, Radboud university medical center, Nijmegen, The Netherlands.
Donders Institute for Brain, Cognition and Behaviour, Radboud University, Nijmegen, The Netherlands.
Neuroscience Biomarkers, Janssen Research and Development, LLC, San Diego, CA, USA.
Department of Genetics & UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Neuropsychiatric Institute, Prince of Wales Hospital, Sydney, NSW, Australia.
Day Clinic for Cognitive Neurology, University Hospital Leipzig, Leipzig, Germany.
Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Departments of Neurology and Epidemiology, University of Washington, Seattle, WA, USA.
Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada.
Departments of Psychology and Psychiatry, University of Toronto, Toronto, ON, Canada.
CHU de Bordeaux, Department of Neurology, F-33000, Bordeaux, France.
Department of Neurology, Erasmus MC, Rotterdam, The Netherlands.

Cortical thickness, surface area and volumes vary with age and cognitive function, and in neurological and psychiatric diseases. Here we report heritability, genetic correlations and genome-wide associations of these cortical measures across the whole cortex, and in 34 anatomically predefined regions. Our discovery sample comprises 22,824 individuals from 20 cohorts within the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. We identify genetic heterogeneity between cortical measures and brain regions, and 160 genome-wide significant associations pointing to wnt/β-catenin, TGF-β and sonic hedgehog pathways. There is enrichment for genes involved in anthropometric traits, hindbrain development, vascular and neurodegenerative disease and psychiatric conditions. These data are a rich resource for studies of the biological mechanisms behind cortical development and aging.

中文翻译：

22,824 名成年人的一般人群样本中皮质结构的遗传相关性和全基因组关联。

皮质厚度、表面积和体积随年龄和认知功能以及神经和精神疾病而变化。在这里，我们报告了整个皮质和 34 个解剖学预定义区域中这些皮质测量值的遗传力、遗传相关性和全基因组关联。我们的发现样本包括来自基因组流行病学心脏和衰老研究队列 (CHARGE) 联盟和英国生物银行 20 个队列的 22,824 名个体。我们确定了皮质测量值和大脑区域之间的遗传异质性，以及 160 个全基因组范围内的显着关联，这些关联指向 wnt/β-连环蛋白、TGF-β 和音刺猬通路。涉及人体测量特征、后脑发育、血管和神经退行性疾病以及精神疾病的基因有所丰富。这些数据是研究皮质发育和衰老背后的生物机制的丰富资源。

更新日期：2020-09-22

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