| Title: | Genomic loci influence patterns of structural covariance in the human brain |
| Journal: | Proceedings of the National Academy of Sciences of the United States of America |
| Published: | 21 Dec 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38127979/ |
| DOI: | https://doi.org/10.1073/pnas.2300842120 |
| URL: | https://pub.dzne.de/record/266752/files/DZNE-2024-00015.pdf |
| Citations: | 8 (8 in last 2 years) as of 8 Aug 2024 |
Publication 9135
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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.</p>
66 Authors
- Junhao Wen
- Ilya M. Nasrallah
- Ahmed Abdulkadir
- Theodore D. Satterthwaite
- Zhijian Yang
- Guray Erus
- Timothy Robert-Fitzgerald
- Ashish Singh
- Aristeidis Sotiras
- Aleix Boquet-Pujadas
- Elizabeth Mamourian
- Jimit Doshi
- Yuhan Cui
- Dhivya Srinivasan
- Ioanna Skampardoni
- Jiong Chen
- Gyujoon Hwang
- Mark Bergman
- Jingxuan Bao
- Yogasudha Veturi
- Zhen Zhou
- Shu Yang
- Paola Dazzan
- Rene S. Kahn
- Hugo G. Schnack
- Marcus V. Zanetti
- Eva Meisenzahl
- Geraldo F. Busatto
- Benedicto Crespo-Facorro
- Christos Pantelis
- Stephen J. Wood
- Chuanjun Zhuo
- Russell T. Shinohara
- Ruben C. Gur
- Raquel E. Gur
- Nikolaos Koutsouleris
- Daniel H. Wolf
- Andrew J. Saykin
- Marylyn D. Ritchie
- Li Shen
- Paul M. Thompson
- Olivier Colliot
- Katharina Wittfeld
- Hans J. Grabe
- Duygu Tosun
- Murat Bilgel
- Yang An
- Daniel S. Marcus
- Pamela LaMontagne
- Susan R. Heckbert
- Thomas R. Austin
- Lenore J. Launer
- Mark Espeland
- Colin L. Masters
- Paul Maruff
- Jurgen Fripp
- Sterling C. Johnson
- John C. Morris
- Marilyn S. Albert
- R. Nick Bryan
- Susan M. Resnick
- Yong Fan
- Mohamad Habes
- David Wolk
- Haochang Shou
- Christos Davatzikos
1 Application
| Application ID | Title |
|---|---|
| 35148 | iSTAGING (Imaging-based coordinate SysTem for AGing and NeurodeGenerative diseases) |
Enabling scientific discoveries that improve human health