Genomic loci influence patterns of structural covariance in the human brain

Junhao Wen; Ilya M. Nasrallah; Ahmed Abdulkadir; Theodore D. Satterthwaite; Zhijian Yang; Guray Erus; Robert Fitzgerald Timothy; Ashish Singh; Aristeidis Sotiras; Aleix Boquet-Pujada; 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-Facorr; 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

doi:10.1073/pnas.2300842120

Genomic loci influence patterns of structural covariance in the human brain

Junhao Wen, Ilya M. Nasrallah, Ahmed Abdulkadir, Theodore D. Satterthwaite, Zhijian Yang, Guray Erus, Robert Fitzgerald Timothy, Ashish Singh, Aristeidis Sotiras, Aleix Boquet-Pujada, Elizabeth Mamourian, Jimit Doshi, Yuhan Cui, Dhivya Srinivasan, Ioanna Skampardoni, Jiong Chen, Gyujoon Hwang, Mark Bergman, Jingxuan Bao, Yogasudha VeturiZhen Zhou, Shu Yang, Paola Dazzan, Rene S. Kahn, Hugo G. Schnack, Marcus V. Zanetti, Eva Meisenzahl, Geraldo F. Busatto, Benedicto Crespo-Facorr, 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

Research output: Contribution to journal › Article › peer-review

6 Scopus 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.

Original language	English
Article number	e2300842120
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	120
Issue number	52
DOIs	https://doi.org/10.1073/pnas.2300842120
State	Published - 2023

Keywords

imaging genetics
matrix factorization
structural covariance

Access to Document

10.1073/pnas.2300842120

Cite this

Wen, J., Nasrallah, I. M., Abdulkadir, A., Satterthwaite, T. D., Yang, Z., Erus, G., Timothy, R. F., Singh, A., Sotiras, A., Boquet-Pujada, A., Mamourian, E., Doshi, J., Cui, Y., Srinivasan, D., Skampardoni, I., Chen, J., Hwang, G., Bergman, M., Bao, J., ... Davatzikos, C. (2023). Genomic loci influence patterns of structural covariance in the human brain. Proceedings of the National Academy of Sciences of the United States of America, 120(52), Article e2300842120. https://doi.org/10.1073/pnas.2300842120

@article{85d6609f53c442eb821d42a12ad31e58,

title = "Genomic loci influence patterns of structural covariance in the human brain",

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.",

keywords = "imaging genetics, matrix factorization, structural covariance",

author = "Junhao Wen and Nasrallah, {Ilya M.} and Ahmed Abdulkadir and Satterthwaite, {Theodore D.} and Zhijian Yang and Guray Erus and Timothy, {Robert Fitzgerald} and Ashish Singh and Aristeidis Sotiras and Aleix Boquet-Pujada and Elizabeth Mamourian and Jimit Doshi and Yuhan Cui and Dhivya Srinivasan and Ioanna Skampardoni and Jiong Chen and Gyujoon Hwang and Mark Bergman and Jingxuan Bao and Yogasudha Veturi and Zhen Zhou and Shu Yang and Paola Dazzan and Kahn, {Rene S.} and Schnack, {Hugo G.} and Zanetti, {Marcus V.} and Eva Meisenzahl and Busatto, {Geraldo F.} and Benedicto Crespo-Facorr and Christos Pantelis and Wood, {Stephen J.} and Chuanjun Zhuo and Shinohara, {Russell T.} and Gur, {Ruben C.} and Gur, {Raquel E.} and Nikolaos Koutsouleris and Wolf, {Daniel H.} and Saykin, {Andrew J.} and Ritchie, {Marylyn D.} and Li Shen and Thompson, {Paul M.} and Olivier Colliot and Katharina Wittfeld and Grabe, {Hans J.} and Duygu Tosun and Murat Bilgel and Yang An and Marcus, {Daniel S.} and Pamela LaMontagne and Heckbert, {Susan R.} and Austin, {Thomas R.} and Launer, {Lenore J.} and Mark Espeland and Masters, {Colin L.} and Paul Maruff and Jurgen Fripp and Johnson, {Sterling C.} and Morris, {John C.} and Albert, {Marilyn S.} and Bryan, {R. Nick} and Resnick, {Susan M.} and Yong Fan and Mohamad Habes and David Wolk and Haochang Shou and Christos Davatzikos",

note = "Publisher Copyright: Copyright {\textcopyright} 2023 the Author(s).",

year = "2023",

doi = "10.1073/pnas.2300842120",

language = "English",

volume = "120",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

issn = "0027-8424",

number = "52",

}

Wen, J, Nasrallah, IM, Abdulkadir, A, Satterthwaite, TD, Yang, Z, Erus, G, Timothy, RF, Singh, A, Sotiras, A, Boquet-Pujada, 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-Facorr, 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 2023, 'Genomic loci influence patterns of structural covariance in the human brain', Proceedings of the National Academy of Sciences of the United States of America, vol. 120, no. 52, e2300842120. https://doi.org/10.1073/pnas.2300842120

TY - JOUR

T1 - Genomic loci influence patterns of structural covariance in the human brain

AU - Wen, Junhao

AU - Nasrallah, Ilya M.

AU - Abdulkadir, Ahmed

AU - Satterthwaite, Theodore D.

AU - Yang, Zhijian

AU - Erus, Guray

AU - Timothy, Robert Fitzgerald

AU - Singh, Ashish

AU - Sotiras, Aristeidis

AU - Boquet-Pujada, Aleix

AU - Mamourian, Elizabeth

AU - Doshi, Jimit

AU - Cui, Yuhan

AU - Srinivasan, Dhivya

AU - Skampardoni, Ioanna

AU - Chen, Jiong

AU - Hwang, Gyujoon

AU - Bergman, Mark

AU - Bao, Jingxuan

AU - Veturi, Yogasudha

AU - Zhou, Zhen

AU - Yang, Shu

AU - Dazzan, Paola

AU - Kahn, Rene S.

AU - Schnack, Hugo G.

AU - Zanetti, Marcus V.

AU - Meisenzahl, Eva

AU - Busatto, Geraldo F.

AU - Crespo-Facorr, Benedicto

AU - Pantelis, Christos

AU - Wood, Stephen J.

AU - Zhuo, Chuanjun

AU - Shinohara, Russell T.

AU - Gur, Ruben C.

AU - Gur, Raquel E.

AU - Koutsouleris, Nikolaos

AU - Wolf, Daniel H.

AU - Saykin, Andrew J.

AU - Ritchie, Marylyn D.

AU - Shen, Li

AU - Thompson, Paul M.

AU - Colliot, Olivier

AU - Wittfeld, Katharina

AU - Grabe, Hans J.

AU - Tosun, Duygu

AU - Bilgel, Murat

AU - An, Yang

AU - Marcus, Daniel S.

AU - LaMontagne, Pamela

AU - Heckbert, Susan R.

AU - Austin, Thomas R.

AU - Launer, Lenore J.

AU - Espeland, Mark

AU - Masters, Colin L.

AU - Maruff, Paul

AU - Fripp, Jurgen

AU - Johnson, Sterling C.

AU - Morris, John C.

AU - Albert, Marilyn S.

AU - Bryan, R. Nick

AU - Resnick, Susan M.

AU - Fan, Yong

AU - Habes, Mohamad

AU - Wolk, David

AU - Shou, Haochang

AU - Davatzikos, Christos

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - imaging genetics

KW - matrix factorization

KW - structural covariance

UR - http://www.scopus.com/inward/record.url?scp=85181179290&partnerID=8YFLogxK

U2 - 10.1073/pnas.2300842120

DO - 10.1073/pnas.2300842120

M3 - Article

C2 - 38127979

AN - SCOPUS:85181179290

SN - 0027-8424

VL - 120

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 52

M1 - e2300842120

ER -

Genomic loci influence patterns of structural covariance in the human brain

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this