Weichen Song1, Wei Qian1, Weidi Wang1,2, Shunying Yu1,2, Guan Ning Lin3,4. 1. Shanghai Mental Health Center, School of Biomedical Engineering, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 200030, Shanghai, China. 2. Shanghai Key Laboratory of Psychotic Disorders, 200030, Shanghai, China. 3. Shanghai Mental Health Center, School of Biomedical Engineering, Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University, 200030, Shanghai, China. nickgnlin@sjtu.edu.cn. 4. Shanghai Key Laboratory of Psychotic Disorders, 200030, Shanghai, China. nickgnlin@sjtu.edu.cn.
Abstract
BACKGROUND: Observational studies have identified various associations between neuroimaging alterations and neuropsychiatric disorders. However, whether such associations could truly reflect causal relations remains still unknown. RESULTS: Here, we leveraged genome-wide association studies (GWAS) summary statistics for (1) 11 psychiatric disorders (sample sizes varied from n = 9,725 to 1,331,010); (2) 110 diffusion tensor imaging (DTI) measurement (sample size n = 17,706); (3) 101 region-of-interest (ROI) volumes, and investigate the causal relationship between brain structures and neuropsychiatric disorders by two-sample Mendelian randomization. Among all DTI-Disorder combinations, we observed a significant causal association between the superior longitudinal fasciculus (SLF) and the risk of Anorexia nervosa (AN) (Odds Ratio [OR] = 0.62, 95 % confidence interval: 0.50 ~ 0.76, P = 6.4 × 10- 6). Similar significant associations were also observed between the body of the corpus callosum (fractional anisotropy) and Alzheimer's disease (OR = 1.07, 95 % CI: 1.03 ~ 1.11, P = 4.1 × 10- 5). By combining all observations, we found that the overall p-value for DTI - Disorder associations was significantly elevated compared to the null distribution (Kolmogorov-Smirnov P = 0.009, inflation factor λ = 1.37), especially for DTI - Bipolar disorder (BP) (λ = 2.64) and DTI - AN (λ = 1.82). In contrast, for ROI-Disorder combinations, we only found a significant association between the brain region of pars triangularis and Schizophrenia (OR = 0.48, 95 % CI: 0.34 ~ 0.69, P = 5.9 × 10- 5) and no overall p-value elevation for ROI-Disorder analysis compared to the null expectation. CONCLUSIONS: As a whole, we show that SLF degeneration may be a risk factor for AN, while DTI variations could be causally related to some neuropsychiatric disorders, such as BP and AN. Also, the white matter structure might have a larger impact on neuropsychiatric disorders than subregion volumes.
BACKGROUND: Observational studies have identified various associations between neuroimaging alterations and neuropsychiatric disorders. However, whether such associations could truly reflect causal relations remains still unknown. RESULTS: Here, we leveraged genome-wide association studies (GWAS) summary statistics for (1) 11 psychiatric disorders (sample sizes varied from n = 9,725 to 1,331,010); (2) 110 diffusion tensor imaging (DTI) measurement (sample size n = 17,706); (3) 101 region-of-interest (ROI) volumes, and investigate the causal relationship between brain structures and neuropsychiatric disorders by two-sample Mendelian randomization. Among all DTI-Disorder combinations, we observed a significant causal association between the superior longitudinal fasciculus (SLF) and the risk of Anorexia nervosa (AN) (Odds Ratio [OR] = 0.62, 95 % confidence interval: 0.50 ~ 0.76, P = 6.4 × 10- 6). Similar significant associations were also observed between the body of the corpus callosum (fractional anisotropy) and Alzheimer's disease (OR = 1.07, 95 % CI: 1.03 ~ 1.11, P = 4.1 × 10- 5). By combining all observations, we found that the overall p-value for DTI - Disorder associations was significantly elevated compared to the null distribution (Kolmogorov-Smirnov P = 0.009, inflation factor λ = 1.37), especially for DTI - Bipolar disorder (BP) (λ = 2.64) and DTI - AN (λ = 1.82). In contrast, for ROI-Disorder combinations, we only found a significant association between the brain region of pars triangularis and Schizophrenia (OR = 0.48, 95 % CI: 0.34 ~ 0.69, P = 5.9 × 10- 5) and no overall p-value elevation for ROI-Disorder analysis compared to the null expectation. CONCLUSIONS: As a whole, we show that SLF degeneration may be a risk factor for AN, while DTI variations could be causally related to some neuropsychiatric disorders, such as BP and AN. Also, the white matter structure might have a larger impact on neuropsychiatric disorders than subregion volumes.
Entities:
Keywords:
Anorexia nervosa; Dysconnectivity; Neuroimaging; Neuropsychiatric disorders; Superior longitudinal fasciculus
Authors: Yingying Tang; Ofer Pasternak; Marek Kubicki; Yogesh Rathi; Tianhong Zhang; Junjie Wang; Huijun Li; Kristen A Woodberry; Lihua Xu; Zhenying Qian; Anni Zhu; Susan Whitfield-Gabrieli; Matcheri S Keshavan; Margaret Niznikiewicz; William S Stone; Robert W McCarley; Martha E Shenton; Jijun Wang; Larry J Seidman Journal: Am J Psychiatry Date: 2019-06-24 Impact factor: 18.112
Authors: Christos Pantelis; Dennis Velakoulis; Patrick D McGorry; Stephen J Wood; John Suckling; Lisa J Phillips; Alison R Yung; Edward T Bullmore; Warrick Brewer; Bridget Soulsby; Patricia Desmond; Philip K McGuire Journal: Lancet Date: 2003-01-25 Impact factor: 79.321
Authors: Martine Hoogman; Janita Bralten; Derrek P Hibar; Maarten Mennes; Marcel P Zwiers; Lizanne S J Schweren; Kimm J E van Hulzen; Sarah E Medland; Elena Shumskaya; Neda Jahanshad; Patrick de Zeeuw; Eszter Szekely; Gustavo Sudre; Thomas Wolfers; Alberdingk M H Onnink; Janneke T Dammers; Jeanette C Mostert; Yolanda Vives-Gilabert; Gregor Kohls; Eileen Oberwelland; Jochen Seitz; Martin Schulte-Rüther; Sara Ambrosino; Alysa E Doyle; Marie F Høvik; Margaretha Dramsdahl; Leanne Tamm; Theo G M van Erp; Anders Dale; Andrew Schork; Annette Conzelmann; Kathrin Zierhut; Ramona Baur; Hazel McCarthy; Yuliya N Yoncheva; Ana Cubillo; Kaylita Chantiluke; Mitul A Mehta; Yannis Paloyelis; Sarah Hohmann; Sarah Baumeister; Ivanei Bramati; Paulo Mattos; Fernanda Tovar-Moll; Pamela Douglas; Tobias Banaschewski; Daniel Brandeis; Jonna Kuntsi; Philip Asherson; Katya Rubia; Clare Kelly; Adriana Di Martino; Michael P Milham; Francisco X Castellanos; Thomas Frodl; Mariam Zentis; Klaus-Peter Lesch; Andreas Reif; Paul Pauli; Terry L Jernigan; Jan Haavik; Kerstin J Plessen; Astri J Lundervold; Kenneth Hugdahl; Larry J Seidman; Joseph Biederman; Nanda Rommelse; Dirk J Heslenfeld; Catharina A Hartman; Pieter J Hoekstra; Jaap Oosterlaan; Georg von Polier; Kerstin Konrad; Oscar Vilarroya; Josep Antoni Ramos-Quiroga; Joan Carles Soliva; Sarah Durston; Jan K Buitelaar; Stephen V Faraone; Philip Shaw; Paul M Thompson; Barbara Franke Journal: Lancet Psychiatry Date: 2017-02-16 Impact factor: 27.083
Authors: Theo G M van Erp; Esther Walton; Derrek P Hibar; Lianne Schmaal; Wenhao Jiang; David C Glahn; Godfrey D Pearlson; Nailin Yao; Masaki Fukunaga; Ryota Hashimoto; Naohiro Okada; Hidenaga Yamamori; Juan R Bustillo; Vincent P Clark; Ingrid Agartz; Bryon A Mueller; Wiepke Cahn; Sonja M C de Zwarte; Hilleke E Hulshoff Pol; René S Kahn; Roel A Ophoff; Neeltje E M van Haren; Ole A Andreassen; Anders M Dale; Nhat Trung Doan; Tiril P Gurholt; Cecilie B Hartberg; Unn K Haukvik; Kjetil N Jørgensen; Trine V Lagerberg; Ingrid Melle; Lars T Westlye; Oliver Gruber; Bernd Kraemer; Anja Richter; David Zilles; Vince D Calhoun; Benedicto Crespo-Facorro; Roberto Roiz-Santiañez; Diana Tordesillas-Gutiérrez; Carmel Loughland; Vaughan J Carr; Stanley Catts; Vanessa L Cropley; Janice M Fullerton; Melissa J Green; Frans A Henskens; Assen Jablensky; Rhoshel K Lenroot; Bryan J Mowry; Patricia T Michie; Christos Pantelis; Yann Quidé; Ulrich Schall; Rodney J Scott; Murray J Cairns; Marc Seal; Paul A Tooney; Paul E Rasser; Gavin Cooper; Cynthia Shannon Weickert; Thomas W Weickert; Derek W Morris; Elliot Hong; Peter Kochunov; Lauren M Beard; Raquel E Gur; Ruben C Gur; Theodore D Satterthwaite; Daniel H Wolf; Aysenil Belger; Gregory G Brown; Judith M Ford; Fabio Macciardi; Daniel H Mathalon; Daniel S O'Leary; Steven G Potkin; Adrian Preda; James Voyvodic; Kelvin O Lim; Sarah McEwen; Fude Yang; Yunlong Tan; Shuping Tan; Zhiren Wang; Fengmei Fan; Jingxu Chen; Hong Xiang; Shiyou Tang; Hua Guo; Ping Wan; Dong Wei; Henry J Bockholt; Stefan Ehrlich; Rick P F Wolthusen; Margaret D King; Jody M Shoemaker; Scott R Sponheim; Lieuwe De Haan; Laura Koenders; Marise W Machielsen; Therese van Amelsvoort; Dick J Veltman; Francesca Assogna; Nerisa Banaj; Pietro de Rossi; Mariangela Iorio; Fabrizio Piras; Gianfranco Spalletta; Peter J McKenna; Edith Pomarol-Clotet; Raymond Salvador; Aiden Corvin; Gary Donohoe; Sinead Kelly; Christopher D Whelan; Erin W Dickie; David Rotenberg; Aristotle N Voineskos; Simone Ciufolini; Joaquim Radua; Paola Dazzan; Robin Murray; Tiago Reis Marques; Andrew Simmons; Stefan Borgwardt; Laura Egloff; Fabienne Harrisberger; Anita Riecher-Rössler; Renata Smieskova; Kathryn I Alpert; Lei Wang; Erik G Jönsson; Sanne Koops; Iris E C Sommer; Alessandro Bertolino; Aurora Bonvino; Annabella Di Giorgio; Emma Neilson; Andrew R Mayer; Julia M Stephen; Jun Soo Kwon; Je-Yeon Yun; Dara M Cannon; Colm McDonald; Irina Lebedeva; Alexander S Tomyshev; Tolibjohn Akhadov; Vasily Kaleda; Helena Fatouros-Bergman; Lena Flyckt; Geraldo F Busatto; Pedro G P Rosa; Mauricio H Serpa; Marcus V Zanetti; Cyril Hoschl; Antonin Skoch; Filip Spaniel; David Tomecek; Saskia P Hagenaars; Andrew M McIntosh; Heather C Whalley; Stephen M Lawrie; Christian Knöchel; Viola Oertel-Knöchel; Michael Stäblein; Fleur M Howells; Dan J Stein; Henk S Temmingh; Anne Uhlmann; Carlos Lopez-Jaramillo; Danai Dima; Agnes McMahon; Joshua I Faskowitz; Boris A Gutman; Neda Jahanshad; Paul M Thompson; Jessica A Turner Journal: Biol Psychiatry Date: 2018-05-14 Impact factor: 12.810
Authors: Jundong Liu; Elizabeth L Chou; Kui Kai Lau; Peter Yat Ming Woo; Tsz Kin Wan; Ruixuan Huang; Kei Hang Katie Chan Journal: HGG Adv Date: 2022-08-10