Novel genomic loci influence patterns of structural covariance in the human brain

• DOI: 10.1101/2022.07.20.22277727
• Publication Date: 2022-07-22T16:35:55Z
• Authors: Junhao Wen; Ilya M. Nasrallah; Ahmed Abdulkadir; Theodore D. Satte...; Zhijian Yang; Guray Erus; Timothy Robert-Fi...; 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-...; Christos Pantelis; Stephen J. Wood; Chuanjun Zhuo; Russell T. Shinohara; Ruben C. Gur; Raquel E. Gur; Nikolaos Koutsoul...; 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
• Keywords: Human brain

Abstract Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across regions individuals during aging diseases. The genetic underpinnings these remain largely unknown. We apply a stochastic multivariate factorization method diverse population 50,699 (12 studies, 130 sites) derive data-driven, multi-scale PSCs regional size. were significantly correlated with 915 genomic loci the discovery set, 617 which are novel, 72% independently replicated. Key pathways influencing involve reelin signaling, apoptosis, neurogenesis, appendage development, while breast cancer indicate potential interplays between metastasis associated neurodegeneration dementia. Using support vector machines, effectively imaging signatures several Our results elucidate new biological human brain. Significance statement changes throughout life, driven by aging, diseases, unexplored regarding their underlying determinants. This study delineates 2003 (PSCs) identifies novel loci, mapped genes enriched implicated development. Overall, provide insights into understanding morphological demonstrate great predicting various neurologic conditions.