Genomic Loci Influence Patterns of Structural Covariance in the Human Brain
J. Wen, I.M. Nasrallah, A. Abdulkadir, T.D. Satterthwaite, Z. Yang, G. Erus, T. Robert-Fitzgerald, A. Singh, A. Sotiras, A. Boquet-Pujadas, E. Mamourian, J. Doshi, Y. Cui, D. Srinivasan, I. Skampardoni, J. Chen, G. Hwang, M. Bergman, J. Bao, Y. Veturi, Z. Zhou, S. Yang, P. Dazzan, R.S. Kahn, H.G. Schnack, M.V. Zanetti, E. Meisenzahl, G.F. Busatto, B. Crespo-Facorro, C. Pantelis, S.J. Wood, C. Zhuo, R.T. Shinohara, R.C. Gur, R.E. Gur, N. Koutsouleris, D.H. Wolf, A.J. Saykin, M.D. Ritchie, L. Shen, P.M. Thompson, O. Colliot, K. Wittfeld, H.J. Grabe, D. Tosun, M. Bilgel, Y. An, D.S. Marcus, P. LaMontagne, S.R. Heckbert, T.R. Austin, L.J. Launer, M. Espeland, C.L. Masters, P. Maruff, J. Fripp, S.C. Johnson, J.C. Morris, M.S. Albert, R.N. Bryan, S.M. Resnick, Y. Fan, M. Habes, D. Wolk, H. Shou, C. Davatzikos
Proceedings of the National Academy of Sciences of the United States of America, vol. 120, no. 52, paper no. e2300842120, December 26, 2023.
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 neuro-degeneration 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.
@ARTICLE(http://bigwww.epfl.ch/publications/wen2301.html, AUTHOR="Wen, J. and Nasrallah, I.M. and Abdulkadir, A. and Satterthwaite, T.D. and Yang, Z. and Erus, G. and Robert-Fitzgerald, T. and Singh, A. and Sotiras, A. and Boquet-Pujadas, A. and Mamourian, E. and Doshi, J. and Cui, Y. and Srinivasan, D. and Skampardoni, I. and Chen, J. and Hwang, G. and Bergman, M. and Bao, J. and Veturi, Y. and Zhou, Z. and Yang, S. and Dazzan, P. and Kahn, R.S. and Schnack, H.G. and Zanetti, M.V. and Meisenzahl, E. and Busatto, G.F. and Crespo-Facorro, B. and Pantelis, C. and Wood, S.J. and Zhuo, C. and Shinohara, R.T. and Gur, R.C. and Gur, R.E. and Koutsouleris, N. and Wolf, D.H. and Saykin, A.J. and Ritchie, M.D. and Shen, L. and Thompson, P.M. and Colliot, O. and Wittfeld, K. and Grabe, H.J. and Tosun, D. and Bilgel, M. and An, Y. and Marcus, D.S. and LaMontagne, P. and Heckbert, S.R. and Austin, T.R. and Launer, L.J. and Espeland, M. and Masters, C.L. and Maruff, P. and Fripp, J. and Johnson, S.C. and Morris, J.C. and Albert, M.S. and Bryan, R.N. and Resnick, S.M. and Fan, Y. and Habes, M. and Wolk, D. and Shou, H. and Davatzikos, C.", 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", YEAR="2023", volume="120", number="52", pages="", month="December 26,", note="paper no.\ e2300842120")