对颅内和皮层下脑容量的基因组分析产生了多基因分数,说明了不同血统之间的差异

IF 31.7 1区 生物学 Q1 GENETICS & HEREDITY Nature genetics Pub Date : 2024-10-21 DOI:10.1038/s41588-024-01951-z
Luis M. García-Marín, Adrian I. Campos, Santiago Diaz-Torres, Jill A. Rabinowitz, Zuriel Ceja, Brittany L. Mitchell, Katrina L. Grasby, Jackson G. Thorp, Ingrid Agartz, Saud Alhusaini, David Ames, Philippe Amouyel, Ole A. Andreassen, Konstantinos Arfanakis, Alejandro Arias-Vasquez, Nicola J. Armstrong, Lavinia Athanasiu, Mark E. Bastin, Alexa S. Beiser, David A. Bennett, Joshua C. Bis, Marco P. M. Boks, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Jan K. Buitelaar, Ralph Burkhardt, Wiepke Cahn, Vince D. Calhoun, Owen T. Carmichael, Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Sven Cichon, Benedicto Crespo-Facorro, Fabrice Crivello, Anders M. Dale, George Davey Smith, Eco J. C. de Geus, Philip L. De Jager, Greig I. de Zubicaray, Stéphanie Debette, Charles DeCarli, Chantal Depondt, Sylvane Desrivières, Srdjan Djurovic, Stefan Ehrlich, Susanne Erk, Thomas Espeseth, Guillén Fernández, Irina Filippi, Simon E. Fisher, Debra A. Fleischman, Evan Fletcher, Myriam Fornage, Andreas J. Forstner, Clyde Francks, Barbara Franke, Tian Ge, Aaron L. Goldman, Hans J. Grabe, Robert C. Green, Oliver Grimm, Nynke A. Groenewold, Oliver Gruber, Vilmundur Gudnason, Asta K. Håberg, Unn K. Haukvik, Andreas Heinz, Derrek P. Hibar, Saima Hilal, Jayandra J. Himali, Beng-Choon Ho, David F. Hoehn, Pieter J. Hoekstra, Edith Hofer, Wolfgang Hoffmann, Avram J. Holmes, Georg Homuth, Norbert Hosten, M. Kamran Ikram, Jonathan C. Ipser, Clifford R. Jack Jr, Neda Jahanshad, Erik G. Jönsson, Rene S. Kahn, Ryota Kanai, Marieke Klein, Maria J. Knol, Lenore J. Launer, Stephen M. Lawrie, Stephanie Le Hellard, Phil H. Lee, Hervé Lemaître, Shuo Li, David C. M. Liewald, Honghuang Lin, W. T. Longstreth Jr, Oscar L. Lopez, Michelle Luciano, Pauline Maillard, Andre F. Marquand, Nicholas G. Martin, Jean-Luc Martinot, Karen A. Mather, Venkata S. Mattay, Katie L. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Nazanin Mirza-Schreiber, Yuri Milaneschi, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Susana Muñoz Maniega, Matthias Nauck, Kwangsik Nho, Wiro J. Niessen, Markus M. Nöthen, Paul A. Nyquist, Jaap Oosterlaan, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. Bruce Pike, Bruce M. Psaty, Benno Pütz, Simone Reppermund, Marcella D. Rietschel, Shannon L. Risacher, Nina Romanczuk-Seiferth, Rafael Romero-Garcia, Gennady V. Roshchupkin, Jerome I. Rotter, Perminder S. Sachdev, Philipp G. Sämann, Arvin Saremi, Muralidharan Sargurupremraj, Andrew J. Saykin, Lianne Schmaal, Helena Schmidt, Reinhold Schmidt, Peter R. Schofield, Markus Scholz, Gunter Schumann, Emanuel Schwarz, Li Shen, Jean Shin, Sanjay M. Sisodiya, Albert V. Smith, Jordan W. Smoller, Hilkka S. Soininen, Vidar M. Steen, Dan J. Stein, Jason L. Stein, Sophia I. Thomopoulos, Arthur W. Toga, Diana Tordesillas-Gutiérrez, Julian N. Trollor, Maria C. Valdes-Hernandez, Dennis van ′t Ent, Hans van Bokhoven, Dennis van der Meer, Nic J. A. van der Wee, Javier Vázquez-Bourgon, Dick J. Veltman, Meike W. Vernooij, Arno Villringer, Louis N. Vinke, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Daniel R. Weinberger, Michael W. Weiner, Wei Wen, Lars T. Westlye, Eric Westman, Tonya White, A. Veronica Witte, Christiane Wolf, Jingyun Yang, Marcel P. Zwiers, M. Arfan Ikram, Sudha Seshadri, Paul M. Thompson, Claudia L. Satizabal, Sarah E. Medland, Miguel E. Rentería
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Fisher, Debra A. Fleischman, Evan Fletcher, Myriam Fornage, Andreas J. Forstner, Clyde Francks, Barbara Franke, Tian Ge, Aaron L. Goldman, Hans J. Grabe, Robert C. Green, Oliver Grimm, Nynke A. Groenewold, Oliver Gruber, Vilmundur Gudnason, Asta K. Håberg, Unn K. Haukvik, Andreas Heinz, Derrek P. Hibar, Saima Hilal, Jayandra J. Himali, Beng-Choon Ho, David F. Hoehn, Pieter J. Hoekstra, Edith Hofer, Wolfgang Hoffmann, Avram J. Holmes, Georg Homuth, Norbert Hosten, M. Kamran Ikram, Jonathan C. Ipser, Clifford R. Jack Jr, Neda Jahanshad, Erik G. Jönsson, Rene S. Kahn, Ryota Kanai, Marieke Klein, Maria J. Knol, Lenore J. Launer, Stephen M. Lawrie, Stephanie Le Hellard, Phil H. Lee, Hervé Lemaître, Shuo Li, David C. M. Liewald, Honghuang Lin, W. T. Longstreth Jr, Oscar L. Lopez, Michelle Luciano, Pauline Maillard, Andre F. Marquand, Nicholas G. Martin, Jean-Luc Martinot, Karen A. Mather, Venkata S. Mattay, Katie L. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Nazanin Mirza-Schreiber, Yuri Milaneschi, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Susana Muñoz Maniega, Matthias Nauck, Kwangsik Nho, Wiro J. Niessen, Markus M. Nöthen, Paul A. Nyquist, Jaap Oosterlaan, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. Bruce Pike, Bruce M. Psaty, Benno Pütz, Simone Reppermund, Marcella D. Rietschel, Shannon L. Risacher, Nina Romanczuk-Seiferth, Rafael Romero-Garcia, Gennady V. Roshchupkin, Jerome I. Rotter, Perminder S. Sachdev, Philipp G. Sämann, Arvin Saremi, Muralidharan Sargurupremraj, Andrew J. Saykin, Lianne Schmaal, Helena Schmidt, Reinhold Schmidt, Peter R. Schofield, Markus Scholz, Gunter Schumann, Emanuel Schwarz, Li Shen, Jean Shin, Sanjay M. Sisodiya, Albert V. Smith, Jordan W. Smoller, Hilkka S. Soininen, Vidar M. Steen, Dan J. Stein, Jason L. Stein, Sophia I. Thomopoulos, Arthur W. Toga, Diana Tordesillas-Gutiérrez, Julian N. 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摘要

皮层下大脑结构与发育、精神和神经系统疾病有关。在这里,我们对 74,898 名欧洲血统参与者的颅内和九个皮层下脑容量(脑干、尾状核、普鲁门、海马、球状苍白球、丘脑、伏隔核、杏仁核和腹侧间脑)进行了全基因组关联研究荟萃分析。我们确定了与这些脑容量相关的 254 个独立基因位点,解释了高达 35% 的表型变异。我们观察了不同分化时间点特定神经细胞类型的基因表达,包括参与细胞内信号转导和大脑衰老相关过程的基因。当应用于不同血统的个体时,脑容量的多基因评分显示出预测能力。我们观察到脑容量对帕金森病和注意力缺陷/多动症的因果遗传效应。研究结果揭示了大脑发育过程中的特定基因表达模式以及合并神经精神疾病的基因变异,这可能会为与脑部疾病有关的风险基因指出大脑基质和作用区域。
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Genomic analysis of intracranial and subcortical brain volumes yields polygenic scores accounting for variation across ancestries
Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon) in 74,898 participants of European ancestry. We identified 254 independent loci associated with these brain volumes, explaining up to 35% of phenotypic variance. We observed gene expression in specific neural cell types across differentiation time points, including genes involved in intracellular signaling and brain aging-related processes. Polygenic scores for brain volumes showed predictive ability when applied to individuals of diverse ancestries. We observed causal genetic effects of brain volumes with Parkinson’s disease and attention-deficit/hyperactivity disorder. Findings implicate specific gene expression patterns in brain development and genetic variants in comorbid neuropsychiatric disorders, which could point to a brain substrate and region of action for risk genes implicated in brain diseases. Genome-wide association analyses of intracranial and nine subcortical brain volumes in 74,898 participants of European ancestry identify 254 independent loci and yield polygenic scores accounting for brain variation across ancestries.
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来源期刊
Nature genetics
Nature genetics 生物-遗传学
CiteScore
43.00
自引率
2.60%
发文量
241
审稿时长
3 months
期刊介绍: Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation. Integrative genetic topics comprise, but are not limited to: -Genes in the pathology of human disease -Molecular analysis of simple and complex genetic traits -Cancer genetics -Agricultural genomics -Developmental genetics -Regulatory variation in gene expression -Strategies and technologies for extracting function from genomic data -Pharmacological genomics -Genome evolution
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