Genomic loci influence patterns of structural covariance in the human brain-Reference-Cited by-同舟云学术

Genomic loci influence patterns of structural covariance in the human brain

Published:2023-12-21 Issue:52 Volume:120 Page:
ISSN:0027-8424
Container-title:Proceedings of the National Academy of Sciences
language:en
Short-container-title:Proc. Natl. Acad. Sci. U.S.A.

Author:

Wen Junhao¹²^ORCID,Nasrallah Ilya M.²³^ORCID,Abdulkadir Ahmed²^ORCID,Satterthwaite Theodore D.²⁴^ORCID,Yang Zhijian²,Erus Guray²,Robert-Fitzgerald Timothy⁵^ORCID,Singh Ashish²,Sotiras Aristeidis⁶^ORCID,Boquet-Pujadas Aleix⁷,Mamourian Elizabeth²,Doshi Jimit²,Cui Yuhan²,Srinivasan Dhivya²,Skampardoni Ioanna²,Chen Jiong²,Hwang Gyujoon²,Bergman Mark²,Bao Jingxuan⁸,Veturi Yogasudha⁹^ORCID,Zhou Zhen²,Yang Shu⁸,Dazzan Paola¹⁰,Kahn Rene S.¹¹,Schnack Hugo G.¹²,Zanetti Marcus V.¹³,Meisenzahl Eva¹⁴,Busatto Geraldo F.¹³^ORCID,Crespo-Facorro Benedicto¹⁵,Pantelis Christos¹⁶^ORCID,Wood Stephen J.¹⁷,Zhuo Chuanjun¹⁸,Shinohara Russell T.²⁵^ORCID,Gur Ruben C.⁴^ORCID,Gur Raquel E.⁴^ORCID,Koutsouleris Nikolaos¹⁹,Wolf Daniel H.²⁴,Saykin Andrew J.²⁰^ORCID,Ritchie Marylyn D.⁹,Shen Li⁸^ORCID,Thompson Paul M.²¹,Colliot Olivier²²,Wittfeld Katharina²³^ORCID,Grabe Hans J.²³,Tosun Duygu²⁴,Bilgel Murat²⁵^ORCID,An Yang²⁵,Marcus Daniel S.⁶,LaMontagne Pamela⁶,Heckbert Susan R.²⁶^ORCID,Austin Thomas R.²⁶,Launer Lenore J.²⁷^ORCID,Espeland Mark²⁸^ORCID,Masters Colin L.²⁹^ORCID,Maruff Paul²⁹^ORCID,Fripp Jurgen³⁰,Johnson Sterling C.³¹,Morris John C.³²,Albert Marilyn S.³³,Bryan R. Nick³^ORCID,Resnick Susan M.²⁵,Fan Yong²^ORCID,Habes Mohamad³⁴^ORCID,Wolk David²³⁵,Shou Haochang²⁵,Davatzikos Christos²

Affiliation:

1. Laboratory of AI and Biomedical Science, Department of Neurology, Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033

2. AI in Biomedical Imaging Laboratory, Department of Radiology, Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104

3. Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104

4. Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104

5. Penn Statistics in Imaging and Visualization Center, Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104

6. Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110

7. Biomedical Imaging Group, Department of Biomedical Engineering, École Polytechnique Fédérale de Lausanne, Lausanne 1015, Switzerland

8. Department of Biostatistics, Epidemiology and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA 19104

9. Department of Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104

10. Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London WC2R 2LS, United Kingdom

11. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY 10029

12. Department of Psychiatry, University Medical Center Utrecht, Utrecht 3584 CX Ut, Netherlands

13. Institute of Psychiatry, Department of Psychiatry, Faculty of Medicine, University of São Paulo, São Paulo 05508-070, Brazil

14. Department of Psychiatry and Psychotherapy, Heinrich Heine University, Düsseldorf 40204, Germany

15. Hospital Universitario Virgen del Rocio, School of Medicine, University of Sevilla, Sevilla 41004, Spain

16. Melbourne Neuropsychiatry Centre, Department of Psychiatry, University of Melbourne, Melbourne, VIC 3052, Australia

17. Orygen and the Centre for Youth Mental Health, Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, VIC 3052, Australia

18. Key Laboratory of Real Tine Tracing of Brain Circuits in Psychiatry and Neurology, Department of Psychiatry, Tianjin Medical University, Tianjin 300070, China

19. Department of Psychiatry and Psychotherapy, Ludwig-Maximilian University, Munich 80539, Germany

20. Indiana Alzheimer’s Disease Research Center, Department of Radiology, Indiana University School of Medicine, Indianapolis, IN 46202-3082

21. Imaging Genetics Center, Department of Neurology, Mark and Mary Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033

22. Institut du Cerveau, Sorbonne Université, Paris 75013, France

23. Department of Psychiatry and Psychotherapy, German Center for Neurodegenerative Diseases, University Medicine Greifswald, Greifswald 17475, Germany

24. Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA 94143

25. Laboratory of Behavioral Neuroscience, National Institute on Aging, NIH, Baltimore 21224, MD

26. Department of Epidemiology, University of Washington, Seattle, WA 98195

27. Neuroepidemiology Section, Intramural Research Program, National Institute on Aging, Washington, MD 20817

28. Sticht Center for Healthy Aging and Alzheimer’s Prevention, Divisions of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC 27101

29. Florey Institute of Neuroscience and Mental Health, Medicine, Dentistry and Health Sciences, The University of Melbourne, Parkville, VIC 3010, Australia

30. Health and Biosecurity, Australian e-Health Research Centre, Commonwealth Scientific and Industrial Research Organisation, Brisbane, QLD 4029, Australia

31. Wisconsin Alzheimer's Institute, Department of Medicine, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792

32. Knight Alzheimer Disease Research Center, Department of Neurology, Washington University in St. Louis, St. Louis, MO 63110

33. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD 21205

34. Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases, Department of Radiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229

35. Department of Neurology, University of Pennsylvania, Philadelphia, PA 19104

Abstract

Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size. PSCs were significantly correlated with 915 genomic loci in the discovery set, 617 of which are newly identified, and 72% were independently replicated. Key pathways influencing PSCs involve reelin signaling, apoptosis, neurogenesis, and appendage development, while pathways of breast cancer indicate potential interplays between brain metastasis and PSCs associated with neurodegeneration and dementia. Using support vector machines, multi-scale PSCs effectively derive imaging signatures of several brain diseases. Our results elucidate genetic and biological underpinnings that influence structural covariance patterns in the human brain.

Funder

National Institutes of Health

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

Link

https://pnas.org/doi/pdf/10.1073/pnas.2300842120

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