Genetic architecture of brain age and its causal relations with brain and mental disorders.
Genetic architecture of brain age and its causal relations with brain and mental disorders.
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脑时代的遗传结构及其与脑和精神障碍的因果关系。
DOI：
10.1038/s41380-023-02087-y
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发表时间：
2023-07
影响因子：
11
通讯作者：
Wang, Yunpeng
中科院分区：
文献类型：
--
作者：
Leonardsen, Esten. H.;Vidal-Pineiro, Didac;Roe, James. M.;Frei, Oleksandr;Shadrin, Alexey. A.;Iakunchykova, Olena;de Lange, Ann-Marie G.;Kaufmann, Tobias;Taschler, Bernd;Smith, Stephen. M.;Andreassen, Ole. A.;Wolfers, Thomas;Westlye, Lars. T.;Wang, Yunpeng
实际年龄和从大脑成像数据估计的大脑表观年龄之间的差异-大脑年龄差距（BAG）-被广泛认为是大脑健康的一般指标。越来越多的证据支持BAG对一系列遗传和非遗传特征和疾病敏感，但很少有研究研究探讨了遗传结构及其与常见脑部疾病的因果关系。在这里，我们使用最先进的神经网络对53，542名个体（年龄范围3-95岁）的大脑扫描进行了训练。对英国生物库28,104名个体（40-84岁）的全基因组关联分析显示，8个独立的基因组区域与BAG显著相关（p < 5 × 10−8），涉及神经、代谢和免疫途径，其中7个是新的。帕金森病、重度抑郁症或精神分裂症与BAG没有显著的遗传相关性或因果关系，但两样本孟德尔随机化表明AD（p = 7.9 × 10−4）和双相情感障碍（p = 1.35 × 10−2）对BAG有因果影响。这些结果强调了大脑年龄的多基因结构，并提供了深入了解选定的神经和神经精神疾病和BAG之间的因果关系。
The difference between chronological age and the apparent age of the brain estimated from brain imaging data—the brain age gap (BAG)—is widely considered a general indicator of brain health. Converging evidence supports that BAG is sensitive to an array of genetic and nongenetic traits and diseases, yet few studies have examined the genetic architecture and its corresponding causal relationships with common brain disorders. Here, we estimate BAG using state-of-the-art neural networks trained on brain scans from 53,542 individuals (age range 3–95 years). A genome-wide association analysis across 28,104 individuals (40–84 years) from the UK Biobank revealed eight independent genomic regions significantly associated with BAG (p < 5 × 10−8) implicating neurological, metabolic, and immunological pathways – among which seven are novel. No significant genetic correlations or causal relationships with BAG were found for Parkinson’s disease, major depressive disorder, or schizophrenia, but two-sample Mendelian randomization indicated a causal influence of AD (p = 7.9 × 10−4) and bipolar disorder (p = 1.35 × 10−2) on BAG. These results emphasize the polygenic architecture of brain age and provide insights into the causal relationship between selected neurological and neuropsychiatric disorders and BAG.
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影响因子：
4.5
作者：
Arbogast T;Iacono G;Chevalier C;Afinowi NO;Houbaert X;van Eede MC;Laliberte C;Birling MC;Linda K;Meziane H;Selloum M;Sorg T;Nadif Kasri N;Koolen DA;Stunnenberg HG;Henkelman RM;Kopanitsa M;Humeau Y;De Vries BBA;Herault Y
通讯作者：
Herault Y
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
通讯作者：
Burgess S
影响因子：
11
作者：
Constantinides, Constantinos;Han, Laura K. M.;Alloza, Clara;Antonucci, Linda Antonella;Arango, Celso;Ayesa-Arriola, Rosa;Banaj, Nerisa;Bertolino, Alessandro;Borgwardt, Stefan;Bruggemann, Jason;Bustillo, Juan;Bykhovski, Oleg;Calhoun, Vince;Carr, Vaughan;Catts, Stanley;Chung, Young-Chul;Crespo-Facorro, Benedicto;Diaz-Caneja, Covadonga M.;Donohoe, Gary;Du Plessis, Stefan;Edmond, Jesse;Ehrlich, Stefan;Emsley, Robin;Eyler, Lisa T.;Fuentes-Claramonte, Paola;Georgiadis, Foivos;Green, Melissa;Guerrero-Pedraza, Amalia;Ha, Minji;Hahn, Tim;Henskens, Frans A.;Holleran, Laurena;Homan, Stephanie;Homan, Philipp;Jahanshad, Neda;Janssen, Joost;Ji, Ellen;Kaiser, Stefan;Kaleda, Vasily;Kim, Minah;Kim, Woo-Sung;Kirschner, Matthias;Kochunov, Peter;Kwak, Yoo Bin;Kwon, Jun Soo;Lebedeva, Irina;Liu, Jingyu;Mitchie, Patricia;Michielse, Stijn;Mothersill, David;Mowry, Bryan;de la Foz, Victor Ortiz-Garcia;Pantelis, Christos;Pergola, Giulio;Piras, Fabrizio;Pomarol-Clotet, Edith;Preda, Adrian;Quide, Yann;Rasser, Paul E.;Rootes-Murdy, Kelly;Salvador, Raymond;Sangiuliano, Marina;Sarro, Salvador;Schall, Ulrich;Schmidt, Andre;Scott, Rodney J.;Selvaggi, Pierluigi;Sim, Kang;Skoch, Antonin;Spalletta, Gianfranco;Spaniel, Filip;Thomopoulos, Sophia, I;Tomecek, David;Tomyshev, Alexander S.;Tordesillas-Gutierrez, Diana;van Amelsvoort, Therese;Vazquez-Bourgon, Javier;Vecchio, Daniela;Voineskos, Aristotle;Weickert, Cynthia S.;Weickert, Thomas;Thompson, Paul M.;Schmaal, Lianne;van Erp, Theo G. M.;Turner, Jessica;Cole, James H.;Dima, Danai;Walton, Esther
通讯作者：
Walton, Esther
影响因子：
11
作者：
Elliott, Maxwell L.;Belsky, Daniel W.;Hariri, Ahmad R.
通讯作者：
Hariri, Ahmad R.