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Genomic loci influence patterns of structural covariance in the human brain. Proc Natl Acad Sci U S A 2023 Dec 26;120(52):e2300842120

Date

12/21/2023

Pubmed ID

38127979

Pubmed Central ID

PMC10756284

DOI

10.1073/pnas.2300842120

Scopus ID

2-s2.0-85181179290 (requires institutional sign-in at Scopus site)   3 Citations

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.

Author List

Wen J, Nasrallah IM, Abdulkadir A, Satterthwaite TD, Yang Z, Erus G, Robert-Fitzgerald T, Singh A, Sotiras A, Boquet-Pujadas A, Mamourian E, Doshi J, Cui Y, Srinivasan D, Skampardoni I, Chen J, Hwang G, Bergman M, Bao J, Veturi Y, Zhou Z, Yang S, Dazzan P, Kahn RS, Schnack HG, Zanetti MV, Meisenzahl E, Busatto GF, Crespo-Facorro B, Pantelis C, Wood SJ, Zhuo C, Shinohara RT, Gur RC, Gur RE, Koutsouleris N, Wolf DH, Saykin AJ, Ritchie MD, Shen L, Thompson PM, Colliot O, Wittfeld K, Grabe HJ, Tosun D, Bilgel M, An Y, Marcus DS, LaMontagne P, Heckbert SR, Austin TR, Launer LJ, Espeland M, Masters CL, Maruff P, Fripp J, Johnson SC, Morris JC, Albert MS, Bryan RN, Resnick SM, Fan Y, Habes M, Wolk D, Shou H, Davatzikos C

Author

Gyujoon Hwang PhD Assistant Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Brain
Brain Mapping
Brain Neoplasms
Genomics
Humans
Magnetic Resonance Imaging