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1. Multi-trait analysis characterizes the genetics of thyroid function and identifies causal associations with clinical implications

Author

Rosalie B. T. M. Sterenborg, Inga Steinbrenner, Yong Li, Melissa N. Bujnis, Tatsuhiko Naito, Eirini Marouli, Tessel E. Galesloot, Oladapo Babajide, Laura Andreasen, Arne Astrup, Bjørn Olav Åsvold, Stefania Bandinelli, Marian Beekman, John P. Beilby, Jette Bork-Jensen, Thibaud Boutin, Jennifer A. Brody, Suzanne J. Brown, Ben Brumpton, Purdey J. Campbell, Anne R. Cappola, Graziano Ceresini, Layal Chaker, Daniel I. Chasman, Maria Pina Concas, Rodrigo Coutinho de Almeida, Simone M. Cross, Francesco Cucca, Ian J. Deary, Alisa Devedzic Kjaergaard, Justin B. Echouffo Tcheugui, Christina Ellervik, Johan G. Eriksson, Luigi Ferrucci, Jan Freudenberg, GHS DiscovEHR, Regeneron Genetics Center, Christian Fuchsberger, Christian Gieger, Franco Giulianini, Martin Gögele, Sarah E. Graham, Niels Grarup, Ivana Gunjača, Torben Hansen, Barbara N. Harding, Sarah E. Harris, Stig Haunsø, Caroline Hayward, Jennie Hui, Till Ittermann, J. Wouter Jukema, Eero Kajantie, Jørgen K. Kanters, Line L. Kårhus, Lambertus A. L. M. Kiemeney, Margreet Kloppenburg, Brigitte Kühnel, Jari Lahti, Claudia Langenberg, Bruno Lapauw, Graham Leese, Shuo Li, David C. M. Liewald, Allan Linneberg, Jesus V. T. Lominchar, Jian’an Luan, Nicholas G. Martin, Antonela Matana, Marcel E. Meima, Thomas Meitinger, Ingrid Meulenbelt, Braxton D. Mitchell, Line T. Møllehave, Samia Mora, Silvia Naitza, Matthias Nauck, Romana T. Netea-Maier, Raymond Noordam, Casia Nursyifa, Yukinori Okada, Stefano Onano, Areti Papadopoulou, Colin N. A. Palmer, Cristian Pattaro, Oluf Pedersen, Annette Peters, Maik Pietzner, Ozren Polašek, Peter P. Pramstaller, Bruce M. Psaty, Ante Punda, Debashree Ray, Paul Redmond, J. Brent Richards, Paul M. Ridker, Tom C. Russ, Kathleen A. Ryan, Morten Salling Olesen, Ulla T. Schultheiss, Elizabeth Selvin, Moneeza K. Siddiqui, Carlo Sidore, P. Eline Slagboom, Thorkild I. A. Sørensen, Enrique Soto-Pedre, Tim D. Spector, Beatrice Spedicati, Sundararajan Srinivasan, John M. Starr, David J. Stott, Toshiko Tanaka, Vesela Torlak, Stella Trompet, Johanna Tuhkanen, André G. Uitterlinden, Erik B. van den Akker, Tibbert van den Eynde, Melanie M. van der Klauw, Diana van Heemst, Charlotte Verroken, W. Edward Visser, Dina Vojinovic, Henry Völzke, Melanie Waldenberger, John P. Walsh, Nicholas J. Wareham, Stefan Weiss, Cristen J. Willer, Scott G. Wilson, Bruce H. R. Wolffenbuttel, Hanneke J. C. M. Wouters, Margaret J. Wright, Qiong Yang, Tatijana Zemunik, Wei Zhou, Gu Zhu, Sebastian Zöllner, Johannes W. A. Smit, Robin P. Peeters, Anna Köttgen, Alexander Teumer, and Marco Medici

Subjects
Science
Abstract

Abstract To date only a fraction of the genetic footprint of thyroid function has been clarified. We report a genome-wide association study meta-analysis of thyroid function in up to 271,040 individuals of European ancestry, including reference range thyrotropin (TSH), free thyroxine (FT4), free and total triiodothyronine (T3), proxies for metabolism (T3/FT4 ratio) as well as dichotomized high and low TSH levels. We revealed 259 independent significant associations for TSH (61% novel), 85 for FT4 (67% novel), and 62 novel signals for the T3 related traits. The loci explained 14.1%, 6.0%, 9.5% and 1.1% of the total variation in TSH, FT4, total T3 and free T3 concentrations, respectively. Genetic correlations indicate that TSH associated loci reflect the thyroid function determined by free T3, whereas the FT4 associations represent the thyroid hormone metabolism. Polygenic risk score and Mendelian randomization analyses showed the effects of genetically determined variation in thyroid function on various clinical outcomes, including cardiovascular risk factors and diseases, autoimmune diseases, and cancer. In conclusion, our results improve the understanding of thyroid hormone physiology and highlight the pleiotropic effects of thyroid function on various diseases.

Published
2024
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2. Multi-site benchmark classification of major depressive disorder using machine learning on cortical and subcortical measures

Author

Vladimir Belov, Tracy Erwin-Grabner, Moji Aghajani, Andre Aleman, Alyssa R. Amod, Zeynep Basgoze, Francesco Benedetti, Bianca Besteher, Robin Bülow, Christopher R. K. Ching, Colm G. Connolly, Kathryn Cullen, Christopher G. Davey, Danai Dima, Annemiek Dols, Jennifer W. Evans, Cynthia H. Y. Fu, Ali Saffet Gonul, Ian H. Gotlib, Hans J. Grabe, Nynke Groenewold, J Paul Hamilton, Ben J. Harrison, Tiffany C. Ho, Benson Mwangi, Natalia Jaworska, Neda Jahanshad, Bonnie Klimes-Dougan, Sheri-Michelle Koopowitz, Thomas Lancaster, Meng Li, David E. J. Linden, Frank P. MacMaster, David M. A. Mehler, Elisa Melloni, Bryon A. Mueller, Amar Ojha, Mardien L. Oudega, Brenda W. J. H. Penninx, Sara Poletti, Edith Pomarol-Clotet, Maria J. Portella, Elena Pozzi, Liesbeth Reneman, Matthew D. Sacchet, Philipp G. Sämann, Anouk Schrantee, Kang Sim, Jair C. Soares, Dan J. Stein, Sophia I. Thomopoulos, Aslihan Uyar-Demir, Nic J. A. van der Wee, Steven J. A. van der Werff, Henry Völzke, Sarah Whittle, Katharina Wittfeld, Margaret J. Wright, Mon-Ju Wu, Tony T. Yang, Carlos Zarate, Dick J. Veltman, Lianne Schmaal, Paul M. Thompson, Roberto Goya-Maldonado, and the ENIGMA Major Depressive Disorder working group

Subjects
Medicine, Science
Abstract

Abstract Machine learning (ML) techniques have gained popularity in the neuroimaging field due to their potential for classifying neuropsychiatric disorders. However, the diagnostic predictive power of the existing algorithms has been limited by small sample sizes, lack of representativeness, data leakage, and/or overfitting. Here, we overcome these limitations with the largest multi-site sample size to date (N = 5365) to provide a generalizable ML classification benchmark of major depressive disorder (MDD) using shallow linear and non-linear models. Leveraging brain measures from standardized ENIGMA analysis pipelines in FreeSurfer, we were able to classify MDD versus healthy controls (HC) with a balanced accuracy of around 62%. But after harmonizing the data, e.g., using ComBat, the balanced accuracy dropped to approximately 52%. Accuracy results close to random chance levels were also observed in stratified groups according to age of onset, antidepressant use, number of episodes and sex. Future studies incorporating higher dimensional brain imaging/phenotype features, and/or using more advanced machine and deep learning methods may yield more encouraging prospects.

Published
2024
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3. The Queensland Twin Adolescent Brain Project, a longitudinal study of adolescent brain development

Author

Lachlan T. Strike, Narelle K. Hansell, Kai-Hsiang Chuang, Jessica L. Miller, Greig I. de Zubicaray, Paul M. Thompson, Katie L. McMahon, and Margaret J. Wright

Subjects
Science
Abstract

Abstract We describe the Queensland Twin Adolescent Brain (QTAB) dataset and provide a detailed methodology and technical validation to facilitate data usage. The QTAB dataset comprises multimodal neuroimaging, as well as cognitive and mental health data collected in adolescent twins over two sessions (session 1: N = 422, age 9–14 years; session 2: N = 304, 10–16 years). The MRI protocol consisted of T1-weighted (MP2RAGE), T2-weighted, FLAIR, high-resolution TSE, SWI, resting-state fMRI, DWI, and ASL scans. Two fMRI tasks were added in session 2: an emotional conflict task and a passive movie-watching task. Outside of the scanner, we assessed cognitive function using standardised tests. We also obtained self-reports of symptoms for anxiety and depression, perceived stress, sleepiness, pubertal development measures, and risk and protective factors. We additionally collected several biological samples for genomic and metagenomic analysis. The QTAB project was established to promote health-related research in adolescence.

Published
2023
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4. Genetic and environmental influences on fruit and vegetable consumption and depression in older adults

Author

Annabel P. Matison, Anbupalam Thalamuthu, Victoria M. Flood, Julian N. Trollor, Vibeke S. Catts, Margaret J. Wright, David Ames, Henry Brodaty, Perminder S. Sachdev, Simone Reppermund, and Karen A. Mather

Subjects
Fruit, Vegetables, Depression, Genetics, Heritability, Twin study, Geriatrics, RC952-954.6
Abstract

Abstract Background Prior work suggests that higher fruit and vegetable consumption may protect against depression in older adults. Better understanding of the influence of genetic and environmental factors on fruit and vegetable intakes may lead to the design of more effective dietary strategies to increase intakes. In turn this may reduce the occurrence of depression in older adults. Objectives The primary aim of this study is to estimate the genetic and environmental influences on the consumption of fruit and vegetables in older adults. The secondary aim is an exploratory analysis into possible shared genetic influences on fruit and vegetable intakes and depression. Methods Analysis of observational data from 374 twins (67.1% female; 208 monozygotic (MZ); 166 dizygotic (DZ)) aged ≥ 65 years drawn from the Older Australian Twins Study. Dietary data were obtained using a validated food frequency questionnaire and depressive symptoms were measured using the 15-item short form Geriatric Depression Scale. The contribution of genetic and environmental influences on fruit and vegetable intake were estimated by comparing MZ and DZ twin intakes using structural equation modelling. A tri-variate twin model was used to estimate the genetic and environmental correlation between total fruit and vegetable intakes and depression. Results In this study, vegetable intake was moderately influenced by genetics (0.39 95%CI 0.22, 0.54). Heritability was highest for brassica vegetables (0.40 95%CI 0.24, 0.54). Overall fruit intake was not significantly heritable. No significant genetic correlations were detected between fruit and vegetable intake and depressive symptoms. Conclusions Vegetable consumption, particularly bitter tasting brassica vegetables, was significantly influenced by genetics, although environmental influences were also apparent. Consumption of fruit was only influenced by the environment, with no genetic influence detected, suggesting strategies targeting the food environment may be particularly effective for encouraging fruit consumption.

Published
2023
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5. 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans

Author

Ida E. Sønderby, Dennis van der Meer, Clara Moreau, Tobias Kaufmann, G. Bragi Walters, Maria Ellegaard, Abdel Abdellaoui, David Ames, Katrin Amunts, Micael Andersson, Nicola J. Armstrong, Manon Bernard, Nicholas B. Blackburn, John Blangero, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Robin Bülow, Rune Bøen, Wiepke Cahn, Vince D. Calhoun, Svenja Caspers, Christopher R. K. Ching, Sven Cichon, Simone Ciufolini, Benedicto Crespo-Facorro, Joanne E. Curran, Anders M. Dale, Shareefa Dalvie, Paola Dazzan, Eco J. C. de Geus, Greig I. de Zubicaray, Sonja M. C. de Zwarte, Sylvane Desrivieres, Joanne L. Doherty, Gary Donohoe, Bogdan Draganski, Stefan Ehrlich, Else Eising, Thomas Espeseth, Kim Fejgin, Simon E. Fisher, Tormod Fladby, Oleksandr Frei, Vincent Frouin, Masaki Fukunaga, Thomas Gareau, Tian Ge, David C. Glahn, Hans J. Grabe, Nynke A. Groenewold, Ómar Gústafsson, Jan Haavik, Asta K. Haberg, Jeremy Hall, Ryota Hashimoto, Jayne Y. Hehir-Kwa, Derrek P. Hibar, Manon H. J. Hillegers, Per Hoffmann, Laurena Holleran, Avram J. Holmes, Georg Homuth, Jouke-Jan Hottenga, Hilleke E. Hulshoff Pol, Masashi Ikeda, Neda Jahanshad, Christiane Jockwitz, Stefan Johansson, Erik G. Jönsson, Niklas R. Jørgensen, Masataka Kikuchi, Emma E. M. Knowles, Kuldeep Kumar, Stephanie Le Hellard, Costin Leu, David E. J. Linden, Jingyu Liu, Arvid Lundervold, Astri Johansen Lundervold, Anne M. Maillard, Nicholas G. Martin, Sandra Martin-Brevet, Karen A. Mather, Samuel R. Mathias, Katie L. McMahon, Allan F. McRae, Sarah E. Medland, Andreas Meyer-Lindenberg, Torgeir Moberget, Claudia Modenato, Jennifer Monereo Sánchez, Derek W. Morris, Thomas W. Mühleisen, Robin M. Murray, Jacob Nielsen, Jan E. Nordvik, Lars Nyberg, Loes M. Olde Loohuis, Roel A. Ophoff, Michael J. Owen, Tomas Paus, Zdenka Pausova, Juan M. Peralta, G. Bruce Pike, Carlos Prieto, Erin B. Quinlan, Céline S. Reinbold, Tiago Reis Marques, James J. H. Rucker, Perminder S. Sachdev, Sigrid B. Sando, Peter R. Schofield, Andrew J. Schork, Gunter Schumann, Jean Shin, Elena Shumskaya, Ana I. Silva, Sanjay M. Sisodiya, Vidar M. Steen, Dan J. Stein, Lachlan T. Strike, Ikuo K. Suzuki, Christian K. Tamnes, Alexander Teumer, Anbupalam Thalamuthu, Diana Tordesillas-Gutiérrez, Anne Uhlmann, Magnus O. Ulfarsson, Dennis van ‘t Ent, Marianne B. M. van den Bree, Pierre Vanderhaeghen, Evangelos Vassos, Wei Wen, Katharina Wittfeld, Margaret J. Wright, Ingrid Agartz, Srdjan Djurovic, Lars T. Westlye, Hreinn Stefansson, Kari Stefansson, Sébastien Jacquemont, Paul M. Thompson, Ole A. Andreassen, and for the ENIGMA-CNV working group

Subjects
Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers—the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Published
2021
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6. Cerebral small vessel disease genomics and its implications across the lifespan

Author

Muralidharan Sargurupremraj, Hideaki Suzuki, Xueqiu Jian, Chloé Sarnowski, Tavia E. Evans, Joshua C. Bis, Gudny Eiriksdottir, Saori Sakaue, Natalie Terzikhan, Mohamad Habes, Wei Zhao, Nicola J. Armstrong, Edith Hofer, Lisa R. Yanek, Saskia P. Hagenaars, Rajan B. Kumar, Erik B. van den Akker, Rebekah E. McWhirter, Stella Trompet, Aniket Mishra, Yasaman Saba, Claudia L. Satizabal, Gregory Beaudet, Laurent Petit, Ami Tsuchida, Laure Zago, Sabrina Schilling, Sigurdur Sigurdsson, Rebecca F. Gottesman, Cora E. Lewis, Neelum T. Aggarwal, Oscar L. Lopez, Jennifer A. Smith, Maria C. Valdés Hernández, Jeroen van der Grond, Margaret J. Wright, Maria J. Knol, Marcus Dörr, Russell J. Thomson, Constance Bordes, Quentin Le Grand, Marie-Gabrielle Duperron, Albert V. Smith, David S. Knopman, Pamela J. Schreiner, Denis A. Evans, Jerome I. Rotter, Alexa S. Beiser, Susana Muñoz Maniega, Marian Beekman, Julian Trollor, David J. Stott, Meike W. Vernooij, Katharina Wittfeld, Wiro J. Niessen, Aicha Soumaré, Eric Boerwinkle, Stephen Sidney, Stephen T. Turner, Gail Davies, Anbupalam Thalamuthu, Uwe Völker, Mark A. van Buchem, R. Nick Bryan, Josée Dupuis, Mark E. Bastin, David Ames, Alexander Teumer, Philippe Amouyel, John B. Kwok, Robin Bülow, Ian J. Deary, Peter R. Schofield, Henry Brodaty, Jiyang Jiang, Yasuharu Tabara, Kazuya Setoh, Susumu Miyamoto, Kazumichi Yoshida, Manabu Nagata, Yoichiro Kamatani, Fumihiko Matsuda, Bruce M. Psaty, David A. Bennett, Philip L. De Jager, Thomas H. Mosley, Perminder S. Sachdev, Reinhold Schmidt, Helen R. Warren, Evangelos Evangelou, David-Alexandre Trégouët, International Network against Thrombosis (INVENT) Consortium, International Headache Genomics Consortium (IHGC), Mohammad A. Ikram, Wei Wen, Charles DeCarli, Velandai K. Srikanth, J. Wouter Jukema, Eline P. Slagboom, Sharon L. R. Kardia, Yukinori Okada, Bernard Mazoyer, Joanna M. Wardlaw, Paul A. Nyquist, Karen A. Mather, Hans J. Grabe, Helena Schmidt, Cornelia M. Van Duijn, Vilmundur Gudnason, William T. Longstreth, Lenore J. Launer, Mark Lathrop, Sudha Seshadri, Christophe Tzourio, Hieab H. Adams, Paul M. Matthews, Myriam Fornage, and Stéphanie Debette

Subjects
Science
Abstract

White matter hyperintensities (WMH) are a common brain-imaging feature of cerebral small vessel disease. Here, the authors carry out a GWAS and followup analyses for WMH-volume, implicating several variants with potential for risk stratification and drug targeting.

Published
2020
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7. Genetic correlations and genome-wide associations of cortical structure in general population samples of 22,824 adults

Author

Edith Hofer, Gennady V. Roshchupkin, Hieab H. H. Adams, Maria J. Knol, Honghuang Lin, Shuo Li, Habil Zare, Shahzad Ahmad, Nicola J. Armstrong, Claudia L. Satizabal, Manon Bernard, Joshua C. Bis, Nathan A. Gillespie, Michelle Luciano, Aniket Mishra, Markus Scholz, Alexander Teumer, Rui Xia, Xueqiu Jian, Thomas H. Mosley, Yasaman Saba, Lukas Pirpamer, Stephan Seiler, James T. Becker, Owen Carmichael, Jerome I. Rotter, Bruce M. Psaty, Oscar L. Lopez, Najaf Amin, Sven J. van der Lee, Qiong Yang, Jayandra J. Himali, Pauline Maillard, Alexa S. Beiser, Charles DeCarli, Sherif Karama, Lindsay Lewis, Mat Harris, Mark E. Bastin, Ian J. Deary, A. Veronica Witte, Frauke Beyer, Markus Loeffler, Karen A. Mather, Peter R. Schofield, Anbupalam Thalamuthu, John B. Kwok, Margaret J. Wright, David Ames, Julian Trollor, Jiyang Jiang, Henry Brodaty, Wei Wen, Meike W. Vernooij, Albert Hofman, André G. Uitterlinden, Wiro J. Niessen, Katharina Wittfeld, Robin Bülow, Uwe Völker, Zdenka Pausova, G. Bruce Pike, Sophie Maingault, Fabrice Crivello, Christophe Tzourio, Philippe Amouyel, Bernard Mazoyer, Michael C. Neale, Carol E. Franz, Michael J. Lyons, Matthew S. Panizzon, Ole A. Andreassen, Anders M. Dale, Mark Logue, Katrina L. Grasby, Neda Jahanshad, Jodie N. Painter, Lucía Colodro-Conde, Janita Bralten, Derrek P. Hibar, Penelope A. Lind, Fabrizio Pizzagalli, Jason L. Stein, Paul M. Thompson, Sarah E. Medland, ENIGMA consortium, Perminder S. Sachdev, William S. Kremen, Joanna M. Wardlaw, Arno Villringer, Cornelia M. van Duijn, Hans J. Grabe, William T. Longstreth, Myriam Fornage, Tomas Paus, Stephanie Debette, M. Arfan Ikram, Helena Schmidt, Reinhold Schmidt, and Sudha Seshadri

Subjects
Science
Abstract

Cortex morphology varies with age, cognitive function, and in neurological and psychiatric diseases. Here the authors report 160 genome-wide significant associations with thickness, surface area and volume of the total cortex and 34 cortical regions from a GWAS meta-analysis in 22,824 adults.

Published
2020
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8. Risk prediction of late-onset Alzheimer’s disease implies an oligogenic architecture

Author

Qian Zhang, Julia Sidorenko, Baptiste Couvy-Duchesne, Riccardo E. Marioni, Margaret J. Wright, Alison M. Goate, Edoardo Marcora, Kuan-lin Huang, Tenielle Porter, Simon M. Laws, Australian Imaging Biomarkers and Lifestyle (AIBL) Study, Perminder S. Sachdev, Karen A. Mather, Nicola J. Armstrong, Anbupalam Thalamuthu, Henry Brodaty, Loic Yengo, Jian Yang, Naomi R. Wray, Allan F. McRae, and Peter M. Visscher

Subjects
Science
Abstract

Despite the identification of genetic risk loci for late-onset Alzheimer’s disease (LOAD), the genetic architecture and prediction remains unclear. Here, the authors use genetic risk scores for prediction of LOAD across three datasets and show evidence suggesting oligogenic variant architecture for this disease.

Published
2020
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9. Large‐scale collaboration in ENIGMA‐EEG: A perspective on the meta‐analytic approach to link neurological and psychiatric liability genes to electrophysiological brain activity

Author

Dirk J. A. Smit, Ole A. Andreassen, Dorret I. Boomsma, Scott J. Burwell, David B. Chorlian, Eco J. C. deGeus, Torbjørn Elvsåshagen, Reyna L. Gordon, Jeremy Harper, Ulrich Hegerl, Tilman Hensch, William G. Iacono, Philippe Jawinski, Erik G. Jönsson, Jurjen J. Luykx, Cyrille L. Magne, Stephen M. Malone, Sarah E. Medland, Jacquelyn L. Meyers, Torgeir Moberget, Bernice Porjesz, Christian Sander, Sanjay M. Sisodiya, Paul M. Thompson, Catharina E. M. vanBeijsterveldt, Edwin vanDellen, Marc Via, and Margaret J. Wright

Subjects
brain disorders, electroencephalography, ENIGMA, harmonization, imaging genetics, open science, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Abstract Background and purpose The ENIGMA‐EEG working group was established to enable large‐scale international collaborations among cohorts that investigate the genetics of brain function measured with electroencephalography (EEG). In this perspective, we will discuss why analyzing the genetics of functional brain activity may be crucial for understanding how neurological and psychiatric liability genes affect the brain. Methods We summarize how we have performed our currently largest genome‐wide association study of oscillatory brain activity in EEG recordings by meta‐analyzing the results across five participating cohorts, resulting in the first genome‐wide significant hits for oscillatory brain function located in/near genes that were previously associated with psychiatric disorders. We describe how we have tackled methodological issues surrounding genetic meta‐analysis of EEG features. We discuss the importance of harmonizing EEG signal processing, cleaning, and feature extraction. Finally, we explain our selection of EEG features currently being investigated, including the temporal dynamics of oscillations and the connectivity network based on synchronization of oscillations. Results We present data that show how to perform systematic quality control and evaluate how choices in reference electrode and montage affect individual differences in EEG parameters. Conclusion The long list of potential challenges to our large‐scale meta‐analytic approach requires extensive effort and organization between participating cohorts; however, our perspective shows that these challenges are surmountable. Our perspective argues that elucidating the genetic of EEG oscillatory activity is a worthwhile effort in order to elucidate the pathway from gene to disease liability.

Published
2021
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10. Using Monozygotic Twins to Dissect Common Genes in Posttraumatic Stress Disorder and Migraine

Author

Charlotte K. Bainomugisa, Heidi G. Sutherland, Richard Parker, Allan F. Mcrae, Larisa M. Haupt, Lyn R. Griffiths, Andrew Heath, Elliot C. Nelson, Margaret J. Wright, Ian B. Hickie, Nicholas G. Martin, Dale R. Nyholt, and Divya Mehta

Subjects
DNA methylation, twins, posttraumatic stress disorder, migraine, genes, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Epigenetic mechanisms have been associated with genes involved in Posttraumatic stress disorder (PTSD). PTSD often co-occurs with other health conditions such as depression, cardiovascular disorder and respiratory illnesses. PTSD and migraine have previously been reported to be symptomatically positively correlated with each other, but little is known about the genes involved. The aim of this study was to understand the comorbidity between PTSD and migraine using a monozygotic twin disease discordant study design in six pairs of monozygotic twins discordant for PTSD and 15 pairs of monozygotic twins discordant for migraine. DNA from peripheral blood was run on Illumina EPIC arrays and analyzed. Multiple testing correction was performed using the Bonferroni method and 10% false discovery rate (FDR). We validated 11 candidate genes previously associated with PTSD including DOCK2, DICER1, and ADCYAP1. In the epigenome-wide scan, seven novel CpGs were significantly associated with PTSD within/near IL37, WNT3, ADNP2, HTT, SLFN11, and NQO2, with all CpGs except the IL37 CpG hypermethylated in PTSD. These results were significantly enriched for genes whose DNA methylation was previously associated with migraine (p-value = 0.036). At 10% FDR, 132 CpGs in 99 genes associated with PTSD were also associated with migraine in the migraine twin samples. Genes associated with PTSD were overrepresented in vascular smooth muscle, axon guidance and oxytocin signaling pathways, while genes associated with both PTSD and migraine were enriched for AMPK signaling and longevity regulating pathways. In conclusion, these results suggest that common genes and pathways are likely involved in PTSD and migraine, explaining at least in part the co-morbidity between the two disorders.

Published
2021
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11. Author Correction: Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J. van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Christina M. Lill, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. De Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Dan Rujescu, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. Van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, and Ian J. Deary

Subjects
Science
Abstract

Christina M. Lill, who contributed to analysis of data, was inadvertently omitted from the author list in the originally published version of this article. This has now been corrected in both the PDF and HTML versions of the article.

Published
2019
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12. Is Healthy Neuroticism Associated with Chronic Conditions? A Coordinated Integrative Data Analysis

Author

Sara J. Weston, Eileen K. Graham, Nicholas A. Turiano, Damaris Aschwanden, Tom Booth, Fleur Harrison, Bryan D. James, Nathan A. Lewis, Steven R. Makkar, Swantje Mueller, Kristi M. Wisniewski, Tomiko Yoneda, Ruixue Zhaoyang, Avron Spiro, Johanna Drewelies, Gert G. Wagner, Elisabeth Steinhagen-Thiessen, Ilja Demuth, Sherry Willis, K. Warner Schaie, Martin Sliwinski, Richard A. Lipton, Mindy Katz, Ian J. Deary, Elizabeth M. Zelinski, David A. Bennett, Perminder S. Sachdev, Henry Brodaty, Julian N. Troller, David Ames, Margaret J. Wright, Denis Gerstorf, Mathias Allemand, Graciela Muniz-Terrera, Andrea M. Piccinin, Scott M. Hofer, and Daniel K. Mroczek

Subjects
healthy neuroticism, conscientiousness, chronic condition, health, coordinated analysis, longitudinal, Psychology, BF1-990
Abstract

Early investigations of the neuroticism by conscientiousness interaction with regards to health have been promising, but to date, there have been no systematic investigations of this interaction that account for the various personality measurement instruments, varying populations, or aspects of health. The current study – the second of three – uses a coordinated analysis approach to test the impact of the neuroticism by conscientiousness interaction on the prevalence and incidence of chronic conditions. Using 15 pre-existing longitudinal studies (N > 49,375), we found that conscientiousness did not moderate the relationship between neuroticism and having hypertension (OR = 1.00,95%CI[0.98,1.02]), diabetes (OR = 1.02[0.99,1.04]), or heart disease (OR = 0.99[0.97,1.01]). Similarly, we found that conscientiousness did not moderate the prospective relationship between neuroticism and onset of hypertension (OR = 0.98[0.95,1.01]), diabetes (OR = 0.99[0.94,1.05]), or heart disease (OR = 0.98[0.94,1.03]). Heterogeneity of effect sizes was largely nonsignificant, with one exception, indicating that the effects are consistent between datasets. Overall, we conclude that there is no evidence that healthy neuroticism, operationalized as the conscientiousness by neuroticism interaction, buffers against chronic conditions.

Published
2020
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13. Region-specific sex differences in the hippocampus

Author

Liza van Eijk, Narelle K. Hansell, Lachlan T. Strike, Baptiste Couvy-Duchesne, Greig I. de Zubicaray, Paul M. Thompson, Katie L. McMahon, Brendan P. Zietsch, and Margaret J. Wright

Subjects
Hippocampus, Hippocampal subfields, Volume, Sex, Gender, Controlling methods, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

The hippocampus is a brain region critical for learning and memory, and is also implicated in several neuropsychiatric disorders that show sex differences in prevalence, symptom expression, and mean age of onset. On average, males have larger hippocampal volumes than females, but findings are inconclusive after adjusting for overall brain size. Although the hippocampus is a heterogenous structure, few studies have focused on sex differences in the hippocampal subfields – with little consensus on whether there are regionally specific sex differences in the hippocampus after adjusting for brain size, or whether it is important to adjust for total hippocampal volume (HPV). Here, using two young adult cohorts from the Queensland Twin IMaging study (QTIM; N ​= ​727) and the Human Connectome Project (HCP; N ​= ​960), we examined differences between males and females in the volumes of 12 hippocampal subfields, extracted using FreeSurfer 6.0. After adjusting the subfield volumes for either HPV or brain size (brain segmentation volume (BSV)) using four controlling methods (allometric, covariate, residual and matching), we estimated the percentage difference of the sex effect (males versus females) and Cohen’s d using hierarchical general linear models. Males had larger volumes compared to females in the parasubiculum (up to 6.04%; Cohen’s d ​= ​0.46) and fimbria (up to 8.75%; d ​= ​0.54) after adjusting for HPV. These sex differences were robust across the two cohorts and multiple controlling methods, though within cohort effect sizes were larger for the matched approach, due to the smaller sub-sample. Additional sex effects were identified in the HCP cohort and combined (QTIM and HCP) sample (hippocampal fissure (up to 6.79%), presubiculum (up to 3.08%), and hippocampal tail (up to −0.23%)). In contrast, no sex differences were detected for the volume of the cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate gyrus (GCDG). These findings show that, independent of differences in HPV, there are regionally specific sex differences in the hippocampus, which may be most prominent in the fimbria and parasubiculum. Further, given sex differences were less consistent across cohorts after controlling for BSV, adjusting for HPV rather than BSV may benefit future studies. This work may help in disentangling sex effects, and provide a better understanding of the implications of sex differences for behaviour and neuropsychiatric disorders.

Published
2020
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14. Is Healthy Neuroticism Associated with Longevity? A Coordinated Integrative Data Analysis

Author

Nicholas A. Turiano, Eileen K. Graham, Sara Weston, Tom Booth, Fleur Harrison, Bryan D. James, Nathan A. Lewis, Steven R. Makkar, Swantje Mueller, Kristi M. Wisniewski, Ruixue Zhaoyang, Avron Spiro, Sherry Willis, K. Warner Schaie, Richard B. Lipton, Mindy Katz, Martin Sliwinski, Ian J. Deary, Elizabeth M. Zelinski, David A. Bennett, Perminder S. Sachdev, Henry Brodaty, Julian N. Trollor, David Ames, Margaret J. Wright, Denis Gerstorf, Graciela Muniz-Terrera, Andrea M. Piccinin, Scott M. Hofer, and Daniel K. Mroczek

Subjects
healthy neuroticism, conscientiousness, big five, ialsa, mortality, coordinated ida, Psychology, BF1-990
Abstract

Individual differences in the Big Five personality traits have emerged as predictors of health and longevity. Although there are robust protective effects for higher levels of conscientiousness, results are mixed for other personality traits. In particular, higher levels of neuroticism have significantly predicted an increased risk of mortality, no-risk at all, and even a reduced risk of dying. The current study hypothesizes that one potential reason for the discrepancy in these findings for neuroticism is that interactions among neuroticism and other key personality traits have largely been ignored. Thus, in the current study we focus on testing whether the personality traits neuroticism and conscientiousness interact to predict mortality. Specifically, we borrow from recent evidence of “healthy neuroticism” to explore whether higher levels of neuroticism are only a risk factor for increased mortality risk when conscientiousness levels are low. We conducted a pre-registered integrative data analysis using 12 different cohort studies (total N = 44,702). Although a consistent pattern emerged of higher levels of conscientiousness predicting a reduced hazard of dying, neuroticism did not show a consistent pattern of prediction. Moreover, no study provided statistical evidence of a neuroticism by conscientiousness interaction. The current findings do not support the idea that the combination of high conscientiousness and high neuroticism can be protective for longevity. Future work is needed to explore different protective factors that may buffer the negative effects of higher levels of neuroticism on health, as well as other behaviors and outcomes that may support the construct of healthy neuroticism.

Published
2020
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15. Is Healthy Neuroticism Associated with Health Behaviors? A Coordinated Integrative Data Analysis

Author

Eileen K. Graham, Sara J. Weston, Nicholas A. Turiano, Damaris Ashwanden, Tom Booth, Fleur Harrison, Bryan D. James, Nathan A. Lewis, Steven R. Makkar, Swantje Mueller, Kristi M. Wisniewski, Tomiko Yoneda, Ruixue Zhaoyang, Avron Spiro, Sherry Willis, K. Warner Schaie, Martin Sliwinski, Richard A. Lipton, Mindy J. Katz, Ian J. Deary, Elizabeth M. Zelinski, David A. Bennett, Perminder S. Sachdev, Henry Brodaty, Julian N. Troller, David Ames, Margaret J. Wright, Denis Gerstorf, Mathias Allemand, Johanna Drewelies, Gert G. Wagner, Graciela Muniz-Terrera, Andrea M. Piccinin, Scott M. Hofer, and Daniel K. Mroczek

Subjects
healthy neuroticism, health behaviors, big five, ialsa, coordinated ida, Psychology, BF1-990
Abstract

Current literature suggests that neuroticism is positively associated with maladaptive life choices, likelihood of disease, and mortality. However, recent research has identified circumstances under which neuroticism is associated with positive outcomes. The current project examined whether “healthy neuroticism”, defined as the interaction of neuroticism and conscientiousness, was associated with the following health behaviors: smoking, alcohol consumption, and physical activity. Using a pre-registered multi-study coordinated integrative data analysis (IDA) approach, we investigated whether “healthy neuroticism” predicted the odds of engaging in each of the aforementioned activities. Each study estimated identical models, using the same covariates and data transformations, enabling optimal comparability of results. These results were then meta-analyzed in order to estimate an average (N-weighted) effect and to ascertain the extent of heterogeneity in the effects. Overall, these results suggest that neuroticism alone was not related to health behaviors, while individuals higher in conscientiousness were less likely to be smokers or drinkers, and more likely to engage in physical activity. In terms of the healthy neuroticism interaction of neuroticism and conscientiousness, significant interactions for smoking and physical activity suggest that the association between neuroticism and health behaviors was smaller among those high in conscientiousness. These findings lend credence to the idea that healthy neuroticism may be linked to certain health behaviors and that these effects are generalizable across several heterogeneous samples.

Published
2020
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16. Educational attainment polygenic scores are associated with cortical total surface area and regions important for language and memory

Author

Brittany L. Mitchell, Gabriel Cuéllar-Partida, Katrina L. Grasby, Adrian I. Campos, Lachlan T. Strike, Liang-Dar Hwang, Aysu Okbay, Paul M. Thompson, Sarah E. Medland, Nicholas G. Martin, Margaret J. Wright, and Miguel E. Rentería

Subjects
Educational attainment, Brain structure, Polygenic scores, Intelligence, Broca’s area, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

It is well established that higher cognitive ability is associated with larger brain size. However, individual variation in intelligence exists despite brain size and recent studies have shown that a simple unifactorial view of the neurobiology underpinning cognitive ability is probably unrealistic. Educational attainment (EA) is often used as a proxy for cognitive ability since it is easily measured, resulting in large sample sizes and, consequently, sufficient statistical power to detect small associations. This study investigates the association between three global (total surface area (TSA), intra-cranial volume (ICV) and average cortical thickness) and 34 regional cortical measures with educational attainment using a polygenic scoring (PGS) approach. Analyses were conducted on two independent target samples of young twin adults with neuroimaging data, from Australia (N ​= ​1097) and the USA (N ​= ​723), and found that higher EA-PGS were significantly associated with larger global brain size measures, ICV and TSA (R2 ​= ​0.006 and 0.016 respectively, p ​

Published
2020
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17. Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Author

David L. Duffy, Gu Zhu, Xin Li, Marianna Sanna, Mark M. Iles, Leonie C. Jacobs, David M. Evans, Seyhan Yazar, Jonathan Beesley, Matthew H. Law, Peter Kraft, Alessia Visconti, John C. Taylor, Fan Liu, Margaret J. Wright, Anjali K. Henders, Lisa Bowdler, Dan Glass, M. Arfan Ikram, André G. Uitterlinden, Pamela A. Madden, Andrew C. Heath, Elliot C. Nelson, Adele C. Green, Stephen Chanock, Jennifer H. Barrett, Matthew A. Brown, Nicholas K. Hayward, Stuart MacGregor, Richard A. Sturm, Alex W. Hewitt, Melanoma GWAS Consortium, Manfred Kayser, David J. Hunter, Julia A. Newton Bishop, Timothy D. Spector, Grant W. Montgomery, David A. Mackey, George Davey Smith, Tamar E. Nijsten, D. Timothy Bishop, Veronique Bataille, Mario Falchi, Jiali Han, and Nicholas G. Martin

Subjects
Science
Abstract

Melanocytic nevus count is associated with melanoma risk. In this study, a meta-analysis of 11 nevus GWAS studies identifies novel SNPs in KITLG and 9q32, and bivariate analysis with melanoma GWAS meta-analysis reveals that most nevus genes affect melanoma risk, while melanoma risk loci do not alter the nevus count.

Published
2018
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18. Genome-wide association study of 23,500 individuals identifies 7 loci associated with brain ventricular volume

Author

Dina Vojinovic, Hieab H. Adams, Xueqiu Jian, Qiong Yang, Albert Vernon Smith, Joshua C. Bis, Alexander Teumer, Markus Scholz, Nicola J. Armstrong, Edith Hofer, Yasaman Saba, Michelle Luciano, Manon Bernard, Stella Trompet, Jingyun Yang, Nathan A. Gillespie, Sven J. van der Lee, Alexander Neumann, Shahzad Ahmad, Ole A. Andreassen, David Ames, Najaf Amin, Konstantinos Arfanakis, Mark E. Bastin, Diane M. Becker, Alexa S. Beiser, Frauke Beyer, Henry Brodaty, R. Nick Bryan, Robin Bülow, Anders M. Dale, Philip L. De Jager, Ian J. Deary, Charles DeCarli, Debra A. Fleischman, Rebecca F. Gottesman, Jeroen van der Grond, Vilmundur Gudnason, Tamara B. Harris, Georg Homuth, David S. Knopman, John B. Kwok, Cora E. Lewis, Shuo Li, Markus Loeffler, Oscar L. Lopez, Pauline Maillard, Hanan El Marroun, Karen A. Mather, Thomas H. Mosley, Ryan L. Muetzel, Matthias Nauck, Paul A. Nyquist, Matthew S. Panizzon, Zdenka Pausova, Bruce M. Psaty, Ken Rice, Jerome I. Rotter, Natalie Royle, Claudia L. Satizabal, Reinhold Schmidt, Peter R. Schofield, Pamela J. Schreiner, Stephen Sidney, David J. Stott, Anbupalam Thalamuthu, Andre G. Uitterlinden, Maria C. Valdés Hernández, Meike W. Vernooij, Wei Wen, Tonya White, A. Veronica Witte, Katharina Wittfeld, Margaret J. Wright, Lisa R. Yanek, Henning Tiemeier, William S. Kremen, David A. Bennett, J. Wouter Jukema, Tomas Paus, Joanna M. Wardlaw, Helena Schmidt, Perminder S. Sachdev, Arno Villringer, Hans Jörgen Grabe, W T Longstreth, Cornelia M. van Duijn, Lenore J. Launer, Sudha Seshadri, M Arfan Ikram, and Myriam Fornage

Subjects
Science
Abstract

An increase in the volume of the brain lateral ventricles is a sign of normal aging, but can also be associated with neurological and psychiatric disorders. Here, Vojinovic et al. identify seven genetic loci in a GWA study for ventricular volume in 23,500 individuals and find correlation with thalamus volume.

Published
2018
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19. Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste

Author

Liang-Dar Hwang, Puya Gharahkhani, Paul A. S. Breslin, Scott D. Gordon, Gu Zhu, Nicholas G. Martin, Danielle R. Reed, and Margaret J. Wright

Subjects
Human, Taste, Perception, Bitter, Receptor, GWAS, Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background Human perception of bitter substances is partially genetically determined. Previously we discovered a single nucleotide polymorphism (SNP) within the cluster of bitter taste receptor genes on chromosome 12 that accounts for 5.8% of the variance in the perceived intensity rating of quinine, and we strengthened the classic association between TAS2R38 genotype and the bitterness of propylthiouracil (PROP). Here we performed a genome-wide association study (GWAS) using a 40% larger sample (n = 1999) together with a bivariate approach to detect previously unidentified common variants with small effects on bitter perception. Results We identified two signals, both with small effects (< 2%), within the bitter taste receptor clusters on chromosomes 7 and 12, which influence the perceived bitterness of denatonium benzoate and sucrose octaacetate respectively. We also provided the first independent replication for an association of caffeine bitterness on chromosome 12. Furthermore, we provided evidence for pleiotropic effects on quinine, caffeine, sucrose octaacetate and denatonium benzoate for the three SNPs on chromosome 12 and the functional importance of the SNPs for denatonium benzoate bitterness. Conclusions These findings provide new insights into the genetic architecture of bitter taste and offer a useful starting point for determining the biological pathways linking perception of bitter substances.

Published
2018
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20. Study of 300,486 individuals identifies 148 independent genetic loci influencing general cognitive function

Author

Gail Davies, Max Lam, Sarah E. Harris, Joey W. Trampush, Michelle Luciano, W. David Hill, Saskia P. Hagenaars, Stuart J. Ritchie, Riccardo E. Marioni, Chloe Fawns-Ritchie, David C. M. Liewald, Judith A. Okely, Ari V. Ahola-Olli, Catriona L. K. Barnes, Lars Bertram, Joshua C. Bis, Katherine E. Burdick, Andrea Christoforou, Pamela DeRosse, Srdjan Djurovic, Thomas Espeseth, Stella Giakoumaki, Sudheer Giddaluru, Daniel E. Gustavson, Caroline Hayward, Edith Hofer, M. Arfan Ikram, Robert Karlsson, Emma Knowles, Jari Lahti, Markus Leber, Shuo Li, Karen A. Mather, Ingrid Melle, Derek Morris, Christopher Oldmeadow, Teemu Palviainen, Antony Payton, Raha Pazoki, Katja Petrovic, Chandra A. Reynolds, Muralidharan Sargurupremraj, Markus Scholz, Jennifer A. Smith, Albert V. Smith, Natalie Terzikhan, Anbupalam Thalamuthu, Stella Trompet, Sven J. van der Lee, Erin B. Ware, B. Gwen Windham, Margaret J. Wright, Jingyun Yang, Jin Yu, David Ames, Najaf Amin, Philippe Amouyel, Ole A. Andreassen, Nicola J. Armstrong, Amelia A. Assareh, John R. Attia, Deborah Attix, Dimitrios Avramopoulos, David A. Bennett, Anne C. Böhmer, Patricia A. Boyle, Henry Brodaty, Harry Campbell, Tyrone D. Cannon, Elizabeth T. Cirulli, Eliza Congdon, Emily Drabant Conley, Janie Corley, Simon R. Cox, Anders M. Dale, Abbas Dehghan, Danielle Dick, Dwight Dickinson, Johan G. Eriksson, Evangelos Evangelou, Jessica D. Faul, Ian Ford, Nelson A. Freimer, He Gao, Ina Giegling, Nathan A. Gillespie, Scott D. Gordon, Rebecca F. Gottesman, Michael E. Griswold, Vilmundur Gudnason, Tamara B. Harris, Annette M. Hartmann, Alex Hatzimanolis, Gerardo Heiss, Elizabeth G. Holliday, Peter K. Joshi, Mika Kähönen, Sharon L. R. Kardia, Ida Karlsson, Luca Kleineidam, David S. Knopman, Nicole A. Kochan, Bettina Konte, John B. Kwok, Stephanie Le Hellard, Teresa Lee, Terho Lehtimäki, Shu-Chen Li, Christina M. Lill, Tian Liu, Marisa Koini, Edythe London, Will T. Longstreth, Oscar L. Lopez, Anu Loukola, Tobias Luck, Astri J. Lundervold, Anders Lundquist, Leo-Pekka Lyytikäinen, Nicholas G. Martin, Grant W. Montgomery, Alison D. Murray, Anna C. Need, Raymond Noordam, Lars Nyberg, William Ollier, Goran Papenberg, Alison Pattie, Ozren Polasek, Russell A. Poldrack, Bruce M. Psaty, Simone Reppermund, Steffi G. Riedel-Heller, Richard J. Rose, Jerome I. Rotter, Panos Roussos, Suvi P. Rovio, Yasaman Saba, Fred W. Sabb, Perminder S. Sachdev, Claudia L. Satizabal, Matthias Schmid, Rodney J. Scott, Matthew A. Scult, Jeannette Simino, P. Eline Slagboom, Nikolaos Smyrnis, Aïcha Soumaré, Nikos C. Stefanis, David J. Stott, Richard E. Straub, Kjetil Sundet, Adele M. Taylor, Kent D. Taylor, Ioanna Tzoulaki, Christophe Tzourio, André Uitterlinden, Veronique Vitart, Aristotle N. Voineskos, Jaakko Kaprio, Michael Wagner, Holger Wagner, Leonie Weinhold, K. Hoyan Wen, Elisabeth Widen, Qiong Yang, Wei Zhao, Hieab H. H. Adams, Dan E. Arking, Robert M. Bilder, Panos Bitsios, Eric Boerwinkle, Ornit Chiba-Falek, Aiden Corvin, Philip L. De Jager, Stéphanie Debette, Gary Donohoe, Paul Elliott, Annette L. Fitzpatrick, Michael Gill, David C. Glahn, Sara Hägg, Narelle K. Hansell, Ahmad R. Hariri, M. Kamran Ikram, J. Wouter Jukema, Eero Vuoksimaa, Matthew C. Keller, William S. Kremen, Lenore Launer, Ulman Lindenberger, Aarno Palotie, Nancy L. Pedersen, Neil Pendleton, David J. Porteous, Katri Räikkönen, Olli T. Raitakari, Alfredo Ramirez, Ivar Reinvang, Igor Rudan, Dan Rujescu, Reinhold Schmidt, Helena Schmidt, Peter W. Schofield, Peter R. Schofield, John M. Starr, Vidar M. Steen, Julian N. Trollor, Steven T. Turner, Cornelia M. Van Duijn, Arno Villringer, Daniel R. Weinberger, David R. Weir, James F. Wilson, Anil Malhotra, Andrew M. McIntosh, Catharine R. Gale, Sudha Seshadri, Thomas H. Mosley, Jan Bressler, Todd Lencz, and Ian J. Deary

Subjects
Science
Abstract

Cognitive function is associated with health and important life outcomes. Here, the authors perform a genome-wide association study for general cognitive function in 300,486 individuals and identify genetic loci that implicate neural and cell developmental pathways in this trait.

Published
2018
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21. Publisher Correction: Novel pleiotropic risk loci for melanoma and nevus density implicate multiple biological pathways

Author

David L. Duffy, Gu Zhu, Xin Li, Marianna Sanna, Mark M. Iles, Leonie C. Jacobs, David M. Evans, Seyhan Yazar, Jonathan Beesley, Matthew H. Law, Peter Kraft, Alessia Visconti, John C. Taylor, Fan Liu, Margaret J. Wright, Anjali K. Henders, Lisa Bowdler, Dan Glass, M. Arfan Ikram, André G. Uitterlinden, Pamela A. Madden, Andrew C. Heath, Elliot C. Nelson, Adele C. Green, Stephen Chanock, Jennifer H. Barrett, Matthew A. Brown, Nicholas K. Hayward, Stuart MacGregor, Richard A. Sturm, Alex W. Hewitt, Melanoma GWAS Consortium, Manfred Kayser, David J. Hunter, Julia A. Newton Bishop, Timothy D. Spector, Grant W. Montgomery, David A. Mackey, George Davey Smith, Tamar E. Nijsten, D. Timothy Bishop, Veronique Bataille, Mario Falchi, Jiali Han, and Nicholas G. Martin

Subjects
Science
Abstract

The original version of this Article contained errors in the spelling of the authors Fan Liu and M. Arfan Ikram, which were incorrectly given as Fan Lui and Arfan M. Ikram. In addition, the original version of this Article also contained errors in the author affiliations which are detailed in the associated Publisher Correction.

Published
2019
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22. Validation and psychometric properties of the Somatic and Psychological HEalth REport (SPHERE) in a young Australian-based population sample using non-parametric item response theory

Author

Baptiste Couvy-Duchesne, Tracey A. Davenport, Nicholas G. Martin, Margaret J. Wright, and Ian B. Hickie

Subjects
Depression, Anxiety, Chronic fatigue, Non-parametric item response theory, Test-retest, Psychometrics, Psychiatry, RC435-571
Abstract

Abstract Background The Somatic and Psychological HEalth REport (SPHERE) is a 34-item self-report questionnaire that assesses symptoms of mental distress and persistent fatigue. As it was developed as a screening instrument for use mainly in primary care-based clinical settings, its validity and psychometric properties have not been studied extensively in population-based samples. Methods We used non-parametric Item Response Theory to assess scale validity and item properties of the SPHERE-34 scales, collected through four waves of the Brisbane Longitudinal Twin Study (N = 1707, mean age = 12, 51% females; N = 1273, mean age = 14, 50% females; N = 1513, mean age = 16, 54% females, N = 1263, mean age = 18, 56% females). We estimated the heritability of the new scores, their genetic correlation, and their predictive ability in a sub-sample (N = 1993) who completed the Composite International Diagnostic Interview. Results After excluding items most responsible for noise, sex or wave bias, the SPHERE-34 questionnaire was reduced to 21 items (SPHERE-21), comprising a 14-item scale for anxiety-depression and a 10-item scale for chronic fatigue (3 items overlapping). These new scores showed high internal consistency (alpha > 0.78), moderate three months reliability (ICC = 0.47–0.58) and item scalability (Hi > 0.23), and were positively correlated (phenotypic correlations r = 0.57–0.70; rG = 0.77–1.00). Heritability estimates ranged from 0.27 to 0.51. In addition, both scores were associated with later DSM-IV diagnoses of MDD, social anxiety and alcohol dependence (OR in 1.23–1.47). Finally, a post-hoc comparison showed that several psychometric properties of the SPHERE-21 were similar to those of the Beck Depression Inventory. Conclusions The scales of SPHERE-21 measure valid and comparable constructs across sex and age groups (from 9 to 28 years). SPHERE-21 scores are heritable, genetically correlated and show good predictive ability of mental health in an Australian-based population sample of young people.

Published
2017
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23. Novel genetic loci associated with hippocampal volume

Author

Derrek P. Hibar, Hieab H. H. Adams, Neda Jahanshad, Ganesh Chauhan, Jason L. Stein, Edith Hofer, Miguel E. Renteria, Joshua C. Bis, Alejandro Arias-Vasquez, M. Kamran Ikram, Sylvane Desrivières, Meike W. Vernooij, Lucija Abramovic, Saud Alhusaini, Najaf Amin, Micael Andersson, Konstantinos Arfanakis, Benjamin S. Aribisala, Nicola J. Armstrong, Lavinia Athanasiu, Tomas Axelsson, Ashley H. Beecham, Alexa Beiser, Manon Bernard, Susan H. Blanton, Marc M. Bohlken, Marco P. Boks, Janita Bralten, Adam M. Brickman, Owen Carmichael, M. Mallar Chakravarty, Qiang Chen, Christopher R. K. Ching, Vincent Chouraki, Gabriel Cuellar-Partida, Fabrice Crivello, Anouk Den Braber, Nhat Trung Doan, Stefan Ehrlich, Sudheer Giddaluru, Aaron L. Goldman, Rebecca F. Gottesman, Oliver Grimm, Michael E. Griswold, Tulio Guadalupe, Boris A. Gutman, Johanna Hass, Unn K. Haukvik, David Hoehn, Avram J. Holmes, Martine Hoogman, Deborah Janowitz, Tianye Jia, Kjetil N. Jørgensen, Nazanin Karbalai, Dalia Kasperaviciute, Sungeun Kim, Marieke Klein, Bernd Kraemer, Phil H. Lee, David C. M. Liewald, Lorna M. Lopez, Michelle Luciano, Christine Macare, Andre F. Marquand, Mar Matarin, Karen A. Mather, Manuel Mattheisen, David R. McKay, Yuri Milaneschi, Susana Muñoz Maniega, Kwangsik Nho, Allison C. Nugent, Paul Nyquist, Loes M. Olde Loohuis, Jaap Oosterlaan, Martina Papmeyer, Lukas Pirpamer, Benno Pütz, Adaikalavan Ramasamy, Jennifer S. Richards, Shannon L. Risacher, Roberto Roiz-Santiañez, Nanda Rommelse, Stefan Ropele, Emma J. Rose, Natalie A. Royle, Tatjana Rundek, Philipp G. Sämann, Arvin Saremi, Claudia L. Satizabal, Lianne Schmaal, Andrew J. Schork, Li Shen, Jean Shin, Elena Shumskaya, Albert V. Smith, Emma Sprooten, Lachlan T. Strike, Alexander Teumer, Diana Tordesillas-Gutierrez, Roberto Toro, Daniah Trabzuni, Stella Trompet, Dhananjay Vaidya, Jeroen Van der Grond, Sven J. Van der Lee, Dennis Van der Meer, Marjolein M. J. Van Donkelaar, Kristel R. Van Eijk, Theo G. M. Van Erp, Daan Van Rooij, Esther Walton, Lars T. Westlye, Christopher D. Whelan, Beverly G. Windham, Anderson M. Winkler, Katharina Wittfeld, Girma Woldehawariat, Christiane Wolf, Thomas Wolfers, Lisa R. Yanek, Jingyun Yang, Alex Zijdenbos, Marcel P. Zwiers, Ingrid Agartz, Laura Almasy, David Ames, Philippe Amouyel, Ole A. Andreassen, Sampath Arepalli, Amelia A. Assareh, Sandra Barral, Mark E. Bastin, Diane M. Becker, James T. Becker, David A. Bennett, John Blangero, Hans van Bokhoven, Dorret I. Boomsma, Henry Brodaty, Rachel M. Brouwer, Han G. Brunner, Randy L. Buckner, Jan K. Buitelaar, Kazima B. Bulayeva, Wiepke Cahn, Vince D. Calhoun, Dara M. Cannon, Gianpiero L. Cavalleri, Ching-Yu Cheng, Sven Cichon, Mark R. Cookson, Aiden Corvin, Benedicto Crespo-Facorro, Joanne E. Curran, Michael Czisch, Anders M. Dale, Gareth E. Davies, Anton J. M. De Craen, Eco J. C. De Geus, Philip L. De Jager, Greig I. De Zubicaray, Ian J. Deary, Stéphanie Debette, Charles DeCarli, Norman Delanty, Chantal Depondt, Anita DeStefano, Allissa Dillman, Srdjan Djurovic, Gary Donohoe, Wayne C. Drevets, Ravi Duggirala, Thomas D. Dyer, Christian Enzinger, Susanne Erk, Thomas Espeseth, Iryna O. Fedko, Guillén Fernández, Luigi Ferrucci, Simon E. Fisher, Debra A. Fleischman, Ian Ford, Myriam Fornage, Tatiana M. Foroud, Peter T. Fox, Clyde Francks, Masaki Fukunaga, J. Raphael Gibbs, David C. Glahn, Randy L. Gollub, Harald H. H. Göring, Robert C. Green, Oliver Gruber, Vilmundur Gudnason, Sebastian Guelfi, Asta K. Håberg, Narelle K. Hansell, John Hardy, Catharina A. Hartman, Ryota Hashimoto, Katrin Hegenscheid, Andreas Heinz, Stephanie Le Hellard, Dena G. Hernandez, Dirk J. Heslenfeld, Beng-Choon Ho, Pieter J. Hoekstra, Wolfgang Hoffmann, Albert Hofman, Florian Holsboer, Georg Homuth, Norbert Hosten, Jouke-Jan Hottenga, Matthew Huentelman, Hilleke E. Hulshoff Pol, Masashi Ikeda, Clifford R. Jack Jr, Mark Jenkinson, Robert Johnson, Erik G. Jönsson, J. Wouter Jukema, René S. Kahn, Ryota Kanai, Iwona Kloszewska, David S. Knopman, Peter Kochunov, John B. Kwok, Stephen M. Lawrie, Hervé Lemaître, Xinmin Liu, Dan L. Longo, Oscar L. Lopez, Simon Lovestone, Oliver Martinez, Jean-Luc Martinot, Venkata S. Mattay, Colm McDonald, Andrew M. McIntosh, Francis J. McMahon, Katie L. McMahon, Patrizia Mecocci, Ingrid Melle, Andreas Meyer-Lindenberg, Sebastian Mohnke, Grant W. Montgomery, Derek W. Morris, Thomas H. Mosley, Thomas W. Mühleisen, Bertram Müller-Myhsok, Michael A. Nalls, Matthias Nauck, Thomas E. Nichols, Wiro J. Niessen, Markus M. Nöthen, Lars Nyberg, Kazutaka Ohi, Rene L. Olvera, Roel A. Ophoff, Massimo Pandolfo, Tomas Paus, Zdenka Pausova, Brenda W. J. H. Penninx, G. Bruce Pike, Steven G. Potkin, Bruce M. Psaty, Simone Reppermund, Marcella Rietschel, Joshua L. Roffman, Nina Romanczuk-Seiferth, Jerome I. Rotter, Mina Ryten, Ralph L. Sacco, Perminder S. Sachdev, Andrew J. Saykin, Reinhold Schmidt, Helena Schmidt, Peter R. Schofield, Sigurdur Sigursson, Andrew Simmons, Andrew Singleton, Sanjay M. Sisodiya, Colin Smith, Jordan W. Smoller, Hilkka Soininen, Vidar M. Steen, David J. Stott, Jessika E. Sussmann, Anbupalam Thalamuthu, Arthur W. Toga, Bryan J. Traynor, Juan Troncoso, Magda Tsolaki, Christophe Tzourio, Andre G. Uitterlinden, Maria C. Valdés Hernández, Marcel Van der Brug, Aad van der Lugt, Nic J. A. van der Wee, Neeltje E. M. Van Haren, Dennis van ’t Ent, Marie-Jose Van Tol, Badri N. Vardarajan, Bruno Vellas, Dick J. Veltman, Henry Völzke, Henrik Walter, Joanna M. Wardlaw, Thomas H. Wassink, Michael E. Weale, Daniel R. Weinberger, Michael W. Weiner, Wei Wen, Eric Westman, Tonya White, Tien Y. Wong, Clinton B. Wright, Ronald H. Zielke, Alan B. Zonderman, Nicholas G. Martin, Cornelia M. Van Duijn, Margaret J. Wright, W. T. Longstreth, Gunter Schumann, Hans J. Grabe, Barbara Franke, Lenore J. Launer, Sarah E. Medland, Sudha Seshadri, Paul M. Thompson, and M. Arfan Ikram

Subjects
Science
Abstract

The hippocampus in mammalian brain varies in size across individuals. Here, Hibar and colleagues perform a genome-wide association meta-analysis to find six genetic loci with significant association to hippocampus volume.

Published
2017
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24. Heritability of the shape of subcortical brain structures in the general population

Author

Gennady V. Roshchupkin, Boris A. Gutman, Meike W. Vernooij, Neda Jahanshad, Nicholas G. Martin, Albert Hofman, Katie L. McMahon, Sven J. van der Lee, Cornelia M. van Duijn, Greig I. de Zubicaray, André G. Uitterlinden, Margaret J. Wright, Wiro J. Niessen, Paul M. Thompson, M. Arfan Ikram, and Hieab H. H. Adams

Subjects
Science
Abstract

The volume of subcortical brain structures is known to be heritable. Here, Roshchupkin and colleagues studied seven different subcortical brain structures in the general population and show that the genetic contributions go beyond these volumetric measurements, and also extend to their shapes.

Published
2016
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25. Cerebral Blood Flow in Community-Based Older Twins Is Moderately Heritable: An Arterial Spin Labeling Perfusion Imaging Study

Author

Jiyang Jiang, Anbupalam Thalamuthu, Forrest C. Koch, Tao Liu, Qun Xu, Julian N. Trollor, David Ames, Margaret J. Wright, Vibeke Catts, Perminder S. Sachdev, and Wei Wen

Subjects
cerebral blood flow, heritability, twin study, community-dwelling, aging, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Adequate cerebral blood flow (CBF) is necessary to maintain brain metabolism and function. Arterial spin labeling (ASL) is an emerging MRI technique offering a non-invasive and reliable quantification of CBF. The genetic basis of CBF has not been well documented, and one approach to investigate this is to examine its heritability. The current study aimed to examine the heritability of CBF using ASL data from a cohort of community-dwelling older twins (41 monozygotic (MZ) and 25 dizygotic (DZ) twin pairs; age range, 65–93 years; 56.4% female). The results showed that the cortex had higher CBF than subcortical gray matter (GM) regions, and CBF in the GM regions of the anterior cerebral artery (ACA) territory was lower than that of the middle (MCA) and posterior (PCA) cerebral arteries. After accounting for the effects of age, sex and scanner, moderate heritability was identified for global CBF (h2 = 0.611; 95% CI = 0.380–0.761), as well as for cortical and subcortical GM and the GM in the major arterial territories (h2 = 0.500–0.612). Strong genetic correlations (GCs) were found between CBF in subcortical and cortical GM regions, as well as among the three arterial territories (ACA, MCA, PCA), suggesting a largely convergent genetic control for the CBF in brain GM. The moderate heritability of CBF warrants future investigations to uncover the genetic variants and genes that regulate CBF.

Published
2019
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26. Homogenizing Estimates of Heritability Among SOLAR-Eclipse, OpenMx, APACE, and FPHI Software Packages in Neuroimaging Data

Author

Peter Kochunov, Binish Patel, Habib Ganjgahi, Brian Donohue, Meghann Ryan, Elliot L. Hong, Xu Chen, Bhim Adhikari, Neda Jahanshad, Paul M. Thompson, Dennis Van’t Ent, Anouk den Braber, Eco J. C. de Geus, Rachel M. Brouwer, Dorret I. Boomsma, Hilleke E. Hulshoff Pol, Greig I. de Zubicaray, Katie L. McMahon, Nicholas G. Martin, Margaret J. Wright, and Thomas E. Nichols

Subjects
DTI, heritability, imaging genetics, reproducability, genetics, population, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571
Abstract

Imaging genetic analyses use heritability calculations to measure the fraction of phenotypic variance attributable to additive genetic factors. We tested the agreement between heritability estimates provided by four methods that are used for heritability estimates in neuroimaging traits. SOLAR-Eclipse and OpenMx use iterative maximum likelihood estimation (MLE) methods. Accelerated Permutation inference for ACE (APACE) and fast permutation heritability inference (FPHI), employ fast, non-iterative approximation-based methods. We performed this evaluation in a simulated twin-sibling pedigree and phenotypes and in diffusion tensor imaging (DTI) data from three twin-sibling cohorts, the human connectome project (HCP), netherlands twin register (NTR) and BrainSCALE projects provided as a part of the enhancing neuro imaging genetics analysis (ENIGMA) consortium. We observed that heritability estimate may differ depending on the underlying method and dataset. The heritability estimates from the two MLE approaches provided excellent agreement in both simulated and imaging data. The heritability estimates for two approximation approaches showed reduced heritability estimates in datasets with deviations from data normality. We propose a data homogenization approach (implemented in solar-eclipse; www.solar-eclipse-genetics.org) to improve the convergence of heritability estimates across different methods. The homogenization steps include consistent regression of any nuisance covariates and enforcing normality on the trait data using inverse Gaussian transformation. Under these conditions, the heritability estimates for simulated and DTI phenotypes produced converging heritability estimates regardless of the method. Thus, using these simple suggestions may help new heritability studies to provide outcomes that are comparable regardless of software package.

Published
2019
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27. Genetic Structure of IQ, Phonemic Decoding Skill, and Academic Achievement

Author

Nikita K. Lazaroo, Timothy C. Bates, Narelle K. Hansell, Margaret J. Wright, Nicholas G. Martin, and Michelle Luciano

Subjects
reading ability, scholastic achievement, multivariate modeling, twin design, intelligence, Genetics, QH426-470
Abstract

The aim of this study was to examine whether phonemic decoding skill (deficits of which characterize dyslexia) shares genetic and/or environmental covariance with scholastic abilities independent of general intelligence. Non-word reading ability, verbal and non-verbal IQ, and standardized academic achievement (Queensland Core Skills Test; QCST) were measured in Australian twins (up to 876 twin pairs and 80 singleton twins). Multivariate genetic analysis showed the presence of a general genetic factor, likely reflecting crystallized ability, which accounted for 45–76% of phenotypic variance in QCST scores, 62% of variance in Verbal IQ, 23% of variance in Performance IQ, and 19% of variance in phonological reading ability. The phonemic decoding genetic factor (explaining 48% of variance in phonemic decoding) was negatively associated with mathematical achievement scores (0.4%). Shared effects of common environment did not explain the relationship between reading ability and academic achievement beyond those also influencing IQ. The unique environmental reading factor (accounting for 26% of variance) influenced academic abilities related to written expression. Future research will need to address whether these reading-specific genetic and unique environment relationships arise from causal effects of reading on scholastic abilities, or whether both share a common influence, such as pleiotropic genes/environmental factors.

Published
2019
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29. The Heritability of Subjective Cognitive Complaints in Older Australian Twins

Author

Amanda E. Selwood, Vibeke S. Catts, Katya Numbers, Teresa Lee, Anbupalam Thalamuthu, Margaret J. Wright, and Perminder S. Sachdev

Subjects
Psychiatry and Mental health, Clinical Psychology, General Neuroscience, General Medicine, Geriatrics and Gerontology
Abstract

Background: Subjective cognitive complaints (SCCs) may be a precursor to mild cognitive impairment (MCI) and dementia. Objective: This study aimed to examine the heritability of SCCs, correlations between SCCs and memory ability, and the influence of personality and mood on these relationships. Methods: Participants were 306 twin pairs. The heritability of SCCs and the genetic correlations between SCCs and memory performance, personality, and mood scores were determined using structural equation modelling. Results: SCCs were low to moderately heritable. Memory performance, personality and mood were genetically, environmentally, and phenotypically correlated with SCCs in bivariate analysis. However, in multivariate analysis, only mood and memory performance had significant correlations with SCCs. Mood appeared to be related to SCCs by an environmental correlation, whereas memory performance was related to SCCs by a genetic correlation. The link between personality and SCCs was mediated by mood. SCCs had a significant amount of both genetic and environmental variances not explained by memory performance, personality, or mood. Conclusion: Our results suggest that SCCs are influenced both by a person’s mood and their memory performance, and that these determinants are not mutually exclusive. While SCCs had genetic overlap with memory performance and environmental association with mood, much of the genetic and environmental components that comprised SCCs were specific to SCCs, though these specific factors are yet to be determined.

Published
2023

36. Persistence of Anxiety/Depression Symptoms in Early Adolescence: A Prospective Study of Daily Life Stress, Rumination, and Daytime Sleepiness in a Genetically Informative Cohort

Author

Narelle K. Hansell, Lachlan T. Strike, Greig I. de Zubicaray, Paul M. Thompson, Katie L. McMahon, and Margaret J. Wright

Subjects
Adolescent, Depression, Pediatrics, Perinatology and Child Health, Humans, Obstetrics and Gynecology, Disorders of Excessive Somnolence, Prospective Studies, Anxiety, Stress, Psychological, Genetics (clinical)
Abstract

In this prospective study of mental health, we examine the influence of three interrelated traits — perceived stress, rumination, and daytime sleepiness — and their association with symptoms of anxiety and depression in early adolescence. Given the known associations between these traits, an important objective is to determine the extent to which they may independently predict anxiety/depression symptoms. Twin pairs from the Queensland Twin Adolescent Brain (QTAB) project were assessed on two occasions (N= 211 pairs aged 9−14 years at baseline and 152 pairs aged 10−16 years at follow-up). Linear regression models and quantitative genetic modeling were used to analyze the data. Prospectively, perceived stress, rumination, and daytime sleepiness accounted for 8−11% of the variation in later anxiety/depression; familial influences contributed strongly to these associations. However, only perceived stress significantly predicted change in anxiety/depression, accounting for 3% of variance at follow-up after adjusting for anxiety/depression at baseline, although it did not do so independently of rumination and daytime sleepiness. Bidirectional effects were found between all traits over time. These findings suggest an underlying architecture that is shared, to some degree, by all traits, while the literature points to hypothalamic–pituitary–adrenal (HPA) axis and/or circadian systems as potential sources of overlapping influence and possible avenues for intervention.

Published
2022

37. Genetic Specificity of Hippocampal Subfield Volumes, Relative to Hippocampal Formation, Identified in 2148 Young Adult Twins and Siblings

Author

Narelle K. Hansell, Lachlan T. Strike, Liza van Eijk, Victoria O’Callaghan, Nicholas G. Martin, Greig I. de Zubicaray, Paul M. Thompson, Katie L. McMahon, and Margaret J. Wright

Subjects
Adult, Young Adult, Siblings, Pediatrics, Perinatology and Child Health, Twins, Brain, Humans, Obstetrics and Gynecology, Hippocampus, Magnetic Resonance Imaging, Genetics (clinical)
Abstract

The hippocampus is a complex brain structure with key roles in cognitive and emotional processing and with subregion abnormalities associated with a range of disorders and psychopathologies. Here we combine data from two large independent young adult twin/sibling cohorts to obtain the most accurate estimates to date of genetic covariation between hippocampal subfield volumes and the hippocampus as a single volume. The combined sample included 2148 individuals, comprising 1073 individuals from 627 families (mean age = 22.3 years) from the Queensland Twin IMaging (QTIM) Study, and 1075 individuals from 454 families (mean age = 28.8 years) from the Human Connectome Project (HCP). Hippocampal subfields were segmented using FreeSurfer version 6.0 (CA4 and dentate gyrus were phenotypically and genetically indistinguishable and were summed to a single volume). Multivariate twin modeling was conducted in OpenMx to decompose variance into genetic and environmental sources. Bivariate analyses of hippocampal formation and each subfield volume showed that 10%–72% of subfield genetic variance was independent of the hippocampal formation, with greatest specificity found for the smaller volumes; for example, CA2/3 with 42% of genetic variance being independent of the hippocampus; fissure (63%); fimbria (72%); hippocampus-amygdala transition area (41%); parasubiculum (62%). In terms of genetic influence, whole hippocampal volume is a good proxy for the largest hippocampal subfields, but a poor substitute for the smaller subfields. Additive genetic sources accounted for 49%–77% of total variance for each of the subfields in the combined sample multivariate analysis. In addition, the multivariate analyses were sufficiently powered to identify common environmental influences (replicated in QTIM and HCP for the molecular layer and CA4/dentate gyrus, and accounting for 7%–16% of total variance for 8 of 10 subfields in the combined sample). This provides the clearest indication yet from a twin study that factors such as home environment may influence hippocampal volumes (albeit, with caveats).

Published
2022

38. Combining meta- and mega- analytic approaches for multi-site diffusion imaging based genetic studies: From the ENIGMA-DTI working group.

Author

Neda Jahanshad, Peter V. Kochunov, Thomas E. Nichols, Emma Sprooten, René C. W. Mandl, Laura Almasy, Rachel M. Brouwer, Joanne E. Curran, Greig I. de Zubicaray, Rali Dimitrova, Peter T. Fox, L. Elliot Hong, Bennett A. Landman, Hervé Lemaître, Lorna M. Lopez, Nicholas G. Martin, Katie L. McMahon, Braxton D. Mitchell, Rene L. Olvera, Charles P. Peterson, Jessika E. Sussmann, Arthur W. Toga, Joanna M. Wardlaw, Margaret J. Wright, Susan N. Wright, Mark E. Bastin, Andrew M. McIntosh, Dorret I. Boomsma, René S. Kahn, Anouk den Braber, Ian J. Deary, Hilleke E. Hulshoff Pol, Douglas Williamson, John Blangero, Dennis van 't Ent, David C. Glahn, and Paul M. Thompson

Published
2014
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40. SCN1A overexpression, associated with a genomic region marked by a risk variant for a common epilepsy, raises seizure susceptibility

Author

Katri Silvennoinen, Kinga Gawel, Despina Tsortouktzidis, Julika Pitsch, Saud Alhusaini, Karen M. J. van Loo, Richard Picardo, Zuzanna Michalak, Susanna Pagni, Helena Martins Custodio, James Mills, Christopher D. Whelan, Greig I. de Zubicaray, Katie L. McMahon, Wietske van der Ent, Karolina J. Kirstein-Smardzewska, Ettore Tiraboschi, Jonathan M. Mudge, Adam Frankish, Maria Thom, Margaret J. Wright, Paul M. Thompson, Susanne Schoch, Albert J. Becker, Camila V. Esguerra, and Sanjay M. Sisodiya

Subjects
Epilepsy, Sclerosis, Genomics, Zebrafish Proteins, Hippocampus, Seizures, Febrile, Pathology and Forensic Medicine, NAV1.1 Voltage-Gated Sodium Channel, Cellular and Molecular Neuroscience, Epilepsy, Temporal Lobe, Animals, Humans, Gliosis, Neurology (clinical), Zebrafish
Abstract

Acta Neuropathol (Berl) 144(1), 107-127 (2022). doi:10.1007/s00401-022-02429-0, Published by Springer, Berlin ; Heidelberg

Published
2022

41. Cortical thickness across the lifespan

Author

Simon E. Fisher, Eveline A. Crone, Dominik Grotegerd, Jilly Naaijen, Anders M. Dale, Sean N. Hatton, Ramona Baur-Streubel, Anthony A. James, Daniel Brandeis, Andrew J. Kalnin, Andreas Reif, Hans-Jörgen Grabe, Pieter J. Hoekstra, Lars Nyberg, Fleur M. Howells, Moji Aghajani, Randy L. Buckner, Daniel A. Rinker, Steven G. Potkin, Dennis van 't Ent, Rachel M. Brouwer, Sophia Frangou, Yang Wang, Nhat Trung Doan, Theodore D. Satterthwaite, Christine Lochner, Geraldo F. Busatto, Lars T. Westlye, Lara M. Wierenga, Calhoun Vd, Henry Brodaty, Carles Soriano-Mas, Annette Conzelmann, Christian K. Tamnes, Julian N. Trollor, Nicholas G. Martin, Neeltje E.M. van Haren, René S. Kahn, Irina Lebedeva, Philip Asherson, Suzanne C. Swagerman, John A. Joska, Theophilus N. Akudjedu, Kang Sim, Lachlan T. Strike, Patricia Gruner, Brenna C. McDonald, Thomas Frodl, Edith Pomarol-Clotet, Víctor Ortiz-García de la Foz, Margaret J. Wright, Norbert Hosten, Jean-Paul Fouche, Bernd Weber, Salvador Sarró, Wei Wen, Dag Alnæs, Greig I. de Zubicaray, Iris E. C. Sommer, Marise W. J. Machielsen, Knut Schnell, Dara M. Cannon, Paola Fuentes-Claramonte, Josiane Bourque, Andreas Meyer-Lindenberg, Anton Albajes-Eizagirre, Sarah Hohmann, Erin W. Dickie, Theo G.M. van Erp, Micael Andersson, Paul Pauli, Thomas Espeseth, Heather C. Whalley, Victoria Chubar, Ruben C. Gur, Tomohiro Nakao, Xavier Caseras, Alessandro Bertolino, Ignacio Martínez-Zalacaín, Katharina Wittfeld, Erick J. Canales-Rodríguez, David C. Glahn, Neda Jahanshad, Jiyang Jiang, Katie L. McMahon, Stefan Borgwardt, Erlend S. Dørum, Jaap Oosterlaan, Won Hee Lee, Alan Breier, Steven Williams, Aristotle N. Voineskos, Bernard Mazoyer, Jordan W. Smoller, Nancy C. Andreasen, Ilya M. Veer, Tiffany M. Chaim-Avancini, Sophie Maingault, Paul M. Thompson, Eco J. C. de Geus, Luisa Lázaro, Giulio Pergola, Efstathios Papachristou, Beng-Choon Ho, David Mataix-Cols, Esther Walton, Ben J. Harrison, Dirk J. Heslenfeld, Pablo Najt, Helena Fatouros-Bergman, Derrek P. Hibar, Gunter Schumann, Raymond Salvador, Lieuwe de Haan, Henry Völzke, Joaquim Radua, Henk Temmingh, Lianne Schmaal, Martine Hoogman, Daniel H. Wolf, Georg C. Ziegler, Marieke Klein, Barbara Franke, Erik G. Jönsson, Laura Koenders, Stefan Ehrlich, Oliver Gruber, Ingrid Agartz, Kun Yang, Ryota Kanai, Sarah Baumeister, Colm McDonald, Annabella Di Giorgio, Amanda Worker, Anne Uhlmann, Marcus V. Zanetti, Danai Dima, Matthew D. Sacchet, Sarah E. Medland, Aurora Bonvino, Benedicto Crespo-Facorro, Jan Egil Nordvik, Joshua L. Roffman, Yannis Paloyelis, Jessica A. Turner, T. P. Klyushnik, Christopher G. Davey, Rachel E. Gur, Ian B. Hickie, Christopher R.K. Ching, Jonna Kuntsi, Tobias Banaschewski, Chaim Huyser, Amirhossein Modabbernia, John D. West, Fabrice Crivello, Núria Bargalló, Patricia J. Conrod, Nic J.A. van der Wee, Mauricio H. Serpa, Thomas H. Wassink, Kathryn I. Alpert, Dick J. Veltman, Andrew J. Saykin, Genevieve McPhilemy, Perminder S. Sachdev, Vincent P. Clark, Ian H. Gotlib, Susanne Erk, Henrik Walter, Dennis van den Meer, Simon Cervenka, Oliver Grimm, Andrew M. McIntosh, Alexander Tomyshev, Francisco X. Castellanos, Bernd Kramer, Klaus-Peter Lesch, Odile A. van den Heuvel, Sophia I. Thomopoulos, Diana Tordesillas-Gutiérrez, Terry L. Jernigan, Yulyia Yoncheva, Anouk den Braber, Jim Lagopoulos, Maria J. Portella, Ole A. Andreassen, Gaelle E. Doucet, Avram J. Holmes, Nynke A. Groenewold, Pedro G.P. Rosa, Hilleke E. Hulshoff Pol, Sanne Koops, José M. Menchón, Jan K. Buitelaar, Dan J. Stein, Dorret I. Boomsma, Lei Wang, C.A. Hartman, Pascual Sánchez-Juan, Andreas Heinz, European Commission, National Institute of Child Health and Human Development (US), QIMR Berghofer Medical Research Institute (Australia), University of Queensland, National Cancer Institute (US), Dutch Research Council, Netherlands Organisation for Health Research and Development, National Institute of Mental Health (US), European Research Council, National Center for Advancing Translational Sciences (US), Medical Research Council (UK), Fundación Marques de Valdecilla, Instituto de Salud Carlos III, Swedish Research Council, South-Eastern Norway Regional Health Authority, Research Council of Norway, Icahn School of Medicine at Mount Sinai, South London and Maudsley NHS Foundation Trust, NHS Foundation Trust, National Institute for Health Research (UK), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Movement Disorder (MD), Developmental Neuroscience in Society, Child and Adolescent Psychiatry / Psychology, Adult Psychiatry, APH - Mental Health, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, General Paediatrics, ARD - Amsterdam Reproduction and Development, Karolinska Schizophrenia Project (KaSP), Ontwikkelingspsychologie (Psychologie, FMG), Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Epidemiology and Data Science, Neurology, Amsterdam Neuroscience - Neurodegeneration, Pediatric surgery, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Amsterdam Neuroscience - Brain Imaging, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Biological Psychology, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Educational and Family Studies, Cognitive Psychology, IBBA, Clinical Neuropsychology, Faculty of Behavioural and Movement Sciences, and APH - Personalized Medicine

Subjects
Male, Aging, Neurologi, Audiology, Trajectories, 0302 clinical medicine, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], Child, Research Articles, Cerebral Cortex, Psychiatry, Aged, 80 and over, Radiological and Ultrasound Technology, Fractional polynomial, 05 social sciences, Radiology, Nuclear Medicine & Medical Imaging, 1. No poverty, Cognition, Middle Aged, Cerebral cortex, Regression, 3. Good health, Escorça cerebral, Neurology, Radiology Nuclear Medicine and imaging, Healthy individuals, Child, Preschool, anatomy & histology [Cerebral Cortex], Female, Analysis of variance, Anatomy, Life Sciences & Biomedicine, Trajectorie, Research Article, Neuroinformatics, Adult, medicine.medical_specialty, Adolescent, Human Development, Clinical Neurology, BF, Neuroimaging, Biology, Development, 050105 experimental psychology, Psykiatri, Cortical thickness, 03 medical and health sciences, Young Adult, Neuroimaging genetics, Envelliment, medicine, Humans, trajectories, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, ddc:610, development, Aged, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], Science & Technology, Brain morphometry, aging, Neurosciences, cortical thickness, Cross-Sectional Studies, RC0321, Neurology (clinical), Neurosciences & Neurology, 030217 neurology & neurosurgery, physiology [Human Development]
Abstract

Special Issue: The ENIGMA Consortium: the first 10 years., Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large-scale studies. In response, we used cross-sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) Consortium to infer age-related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta-analysis and one-way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes., European Community's Seventh Framework Programme, Grant/Award Numbers: 278948, 602450, 603016, 602805; US National Institute of Child Health and Human Development, Grant/Award Numbers: RO1HD050735, 1009064, 496682; QIMR Berghofer Medical Research Institute and the Centre for Advanced Imaging, University of Queensland; ICTSI NIH/NCRR, Grant/Award Number: RR025761; European Community's Horizon 2020 Programme, Grant/Award Numbers: 667302, 643051; Vici Innovation Program, Grant/Award Numbers: #91619115, 016-130-669; NWO Brain & Cognition Excellence Program, Grant/Award Number: 433-09-229; Biobanking and Biomolecular Resources Research Infrastructure (Netherlands) (BBMRI-NL); Spinozapremie, Grant/Award Number: NWO-56-464-14192; Biobanking and Biomolecular Resources Research Infrastructure, Grant/Award Numbers: 184.033.111, 184.021.007; Netherlands Organization for Health Research and Development (ZonMW), Grant/Award Numbers: 480-15-001/674, 024.001.003, 911-09-032, 056-32-010, 481-08-011, 016-115-035, 31160008, 400-07-080, 400-05-717, 451-04-034, 463-06-001, 480-04-004, 904-61-193, 912-10-020, 985-10-002, 904-61-090; NIMH, Grant/Award Number: R01 MH090553; Geestkracht programme of the Dutch Health Research Council, Grant/Award Number: 10-000-1001; FP7 Ideas: European Research Council; Nederlandse Organisatie voor Wetenschappelijk Onderzoek, Grant/Award Numbers: NWO/SPI 56-464-14192, NWO-MagW 480-04-004, 433-09-220, NWO 51.02.062, NWO 51.02.061; National Center for Advancing Translational Sciences, National Institutes of Health, Grant/Award Number: UL1 TR000153; National Center for Research Resources; National Center for Research Resources at the National Institutes of Health, Grant/Award Numbers: NIH 1U24 RR025736-01, NIH 1U24 RR021992; NIH Institutes contributing to the Big Data to Knowledge; U.S. National Institutes of Health, Grant/Award Numbers: R01 CA101318, P30 AG10133, R01 AG19771; Medical Research Council, Grant/Award Numbers: U54EB020403, G0500092; National Institute of Mental Health, Grant/Award Numbers: R01MH117014, R01MH042191; Fundación Instituto de Investigación Marqués de Valdecilla, Grant/Award Numbers: API07/011, NCT02534363, NCT0235832; Instituto de Salud Carlos III, Grant/Award Numbers: PI14/00918, PI14/00639, PI060507, PI050427, PI020499; Swedish Research Council, Grant/Award Numbers: 523-2014-3467, 2017-00949, 521-2014-3487; South-Eastern Norway Health Authority; the Research Council of Norway, Grant/Award Number: 223273; South Eastern Norway Regional Health Authority, Grant/Award Numbers: 2017-112, 2019107; Icahn School of Medicine at Mount Sinai; Seventh Framework Programme (FP7/2007-2013), Grant/Award Number: 602450; National Institutes of Health, Grant/Award Numbers: R01 MH116147, R01 MH113619, R01 MH104284; South London and Maudsley NHS Foundation Trust; the National Institute for Health Research (NIHR)

Published
2022

42. Greater male than female variability in regional brain structure across the lifespan

Author

Erick J. Canales-Rodríguez, Hans J. Grabe, Dirk J. Heslenfeld, Erik G. Jönsson, Oliver Gruber, Daniel Brandeis, Yang Wang, Henry Brodaty, Ruben C. Gur, Iris E. C. Sommer, Paul M. Thompson, Knut K. Kolskår, Christopher G. Davey, Dick J. Veltman, Eco J. C. de Geus, Tobias Banaschewski, Greig I. Zubicaray, Xavier Caseras, Sarah Baumeister, Raquel E. Gur, Vincent P. Clark, Maria J. Portella, Simon E. Fisher, Christopher R.K. Ching, Lars T. Westlye, Laura Koenders, Vince D. Calhoun, Carles Soriano-Mas, Nicholas G. Martin, Stefan Ehrlich, Fleur M. Howells, Catharina A. Hartman, Matthew D. Sacchet, Ole A. Andreassen, Josiane Bourque, Fabrice Crivello, Annette Conzelmann, Jaap Oosterlaan, Brenna C. McDonald, Gaelle E. Doucet, Avram J. Holmes, José M. Menchón, Danai Dima, Moji Aghajani, Joshua L. Roffman, Steven Williams, Lei Wang, David Mataix-Cols, Philip R. Szeszko, Bernd Weber, Tiril P. Gurholt, Sarah Hohmann, Ian H. Gotlib, Patricia Gruner, Anthony C. James, Paul Pauli, Lara M. Wierenga, Andrew M. McIntosh, Andrew J. Kalnin, Jim Lagopoulos, Henrik Walter, Andreas Reif, Andrew Simmons, Norbert Hosten, Pieter J. Hoekstra, Aristotle Voineskos, Alexander Tomyshev, Anton Albajes-Eizagirre, Jean-Paul Fouche, Dara M. Cannon, Ignacio Martínez‐Zalacaín, Geneviève Richard, Theophilus N. Akudjedu, David C. Glahn, Patricia J. Conrod, Ben J. Harrison, Alan Anticevic, Martine Hoogman, Francisco X. Castellanos, Bernd Kramer, Neda Jahanshad, Lieuwe de Haan, Dennis van der Meer, John D. West, Alan Breier, Jordan W. Smoller, P. G. P. Rosa, Katharina Wittfeld, Dan J. Stein, Jiyang Jiang, Jilly Naaijen, Christine Lochner, Dorret I. Boomsma, Alessandro Bertolino, Marise W. J. Machielsen, Hilleke E. Hulshoff Pol, Henry Völzke, Christian K. Tamnes, Ingrid Agartz, Georg C. Ziegler, Marieke Klein, Lars Nyberg, Perminder S. Sachdev, Philip Asherson, I.M. Veer, Sean N. Hatton, Núria Bargalló, Annabella Di Giorgio, Henk Temmingh, John A. Joska, Odile A. van den Heuvel, Wei Wen, Eveline A Crone, Kang Sim, Kathryn I. Alpert, Dennis van 't Ent, Jan K. Buitelaar, Joaquim Radua, Julian N. Trollor, B Mazoyer, Chaim Huyser, H. C. Whalley, Irina Lebedeva, Erin W. Dickie, Marcus Vinicus Zanetti, Stefan Borgwardt, Theodore D. Satterthwaite, Daniel H Wolf, Sophia I. Thomopoulos, Giulio Pergola, Luisa Lazaro, Ramona Baur-Streubel, Beathe Haatveit, Yannis Paloyelis, Ian B. Hickie, Jonna Kuntsi, Sophia Frangou, R. Salvador, Geraldo F. Busatto, Margaret J. Wright, Aurora Bonvino, Edith Pomarol-Clotet, Anouk den Braber, Lachlan T. Strike, Phil Lee, Anne Uhlmann, Yuliya N. Yoncheva, Mauricio H. Serpa, Dag Alnæs, Paola Fuentes-Claramonte, Katie L. McMahon, Andrew J. Saykin, Genevieve McPhilemy, Tiffany M. Chaim-Avancini, Sophie Maingault, Barbara Franke, Colm McDonald, Rachel M. Brouwer, Salvador Sarró, Department of Psychology, Education and Child Studies, Biological Psychology, APH - Mental Health, APH - Methodology, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, AMS - Ageing & Vitality, AMS - Sports, APH - Personalized Medicine, Cognitive Psychology, Clinical Neuropsychology, IBBA, Karolinska Schizophrenia Project (KaSP) Consortium, Adult Psychiatry, ANS - Complex Trait Genetics, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Child Psychiatry, ANS - Cellular & Molecular Mechanisms, ANS - Amsterdam Neuroscience, General Paediatrics, ARD - Amsterdam Reproduction and Development, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Movement Disorder (MD), Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, Neurology, Amsterdam Neuroscience - Neurodegeneration, Anatomy and neurosciences, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Pediatric surgery, and Amsterdam Neuroscience - Brain Imaging

Subjects
Male, Netherlands Twin Register (NTR), SEGMENTATION, Vulnerability, Disease, HM, 0302 clinical medicine, Anàlisi de variància, 130 000 Cognitive Neurology & Memory, diagnostic imaging [Cerebral Cortex], sexual characteristics, Analysis of variance, nuclear magnetic resonance imaging, Cervell, Research Articles, Cerebral Cortex, Sex Characteristics, Radiological and Ultrasound Technology, 05 social sciences, Brain, clinical trial, Brain Structure, Magnetic Resonance Imaging, Early life, Adolescence, medicine.anatomical_structure, Neurology, Cerebral cortex, Healthy individuals, X-CHROMOSOME, anatomy & histology [Cerebral Cortex], Evolution of the brain, Female, Anatomy, Neurovetenskaper, Research Article, Radiology, Nuclear Medicine and Medical Imaging, Neuroinformatics, SEX-DIFFERENCES, diagnostic imaging, brain, Human Development, BF, Neuroimaging, SURFACE-AREA, Evolució del cervell, Regional area, Biology, MULTISAMPLE, 050105 experimental psychology, brain cortex, 03 medical and health sciences, CEREBRAL-CORTEX, Sex differences, medicine, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, human, ddc:610, Cortical surface, GENERAL INTELLIGENCE, diagnostic imaging [Brain], METAANALYSIS, biological variation, HUMAN HIPPOCAMPUS, Neurodevelopmental disorders Donders Center for Medical Neuroscience [Radboudumc 7], physiology [Biological Variation, Population], Neurosciences, Gender, Brain Cortical Thickness, multicenter study, Biological Variation, Population, Diferències entre sexes, physiology, RC0321, Radiologi och bildbehandling, Neurology (clinical), anatomy & histology [Brain], 170 000 Motivational & Cognitive Control, 030217 neurology & neurosurgery, anatomy and histology, meta analysis, physiology [Human Development], Demography
Abstract

Contains fulltext : 248376.pdf (Publisher’s version ) (Open Access) For many traits, males show greater variability than females, with possible implications for understanding sex differences in health and disease. Here, the ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) Consortium presents the largest-ever mega-analysis of sex differences in variability of brain structure, based on international data spanning nine decades of life. Subcortical volumes, cortical surface area and cortical thickness were assessed in MRI data of 16,683 healthy individuals 1-90 years old (47% females). We observed significant patterns of greater male than female between-subject variance for all subcortical volumetric measures, all cortical surface area measures, and 60% of cortical thickness measures. This pattern was stable across the lifespan for 50% of the subcortical structures, 70% of the regional area measures, and nearly all regions for thickness. Our findings that these sex differences are present in childhood implicate early life genetic or gene-environment interaction mechanisms. The findings highlight the importance of individual differences within the sexes, that may underpin sex-specific vulnerability to disorders.

Published
2022

43. Normative Modeling of Brain Morphometry Across the Lifespan using CentileBrain: Algorithm Benchmarking and Model Optimization

Author

Ruiyang Ge, Yuetong Yu, Yi Xuan Qi, Yunan Vera Fan, Shiyu Chen, Chuntong Gao, Shalaila S Haas, Amirhossein Modabbernia, Faye New, Ingrid Agartz, Philip Asherson, Rosa Ayesa-Arriola, Nerisa Banaj, Tobias Banaschewski, Sarah Baumeister, Alessandro Bertolino, Dorret I Boomsma, Stefan Borgwardt, Josiane Bourque, Daniel Brandeis, Alan Breier, Henry Brodaty, Rachel M Brouwer, Randy Buckner, Jan K Buitelaar, Dara M Cannon, Xavier Caseras, Simon Cervenka, Patricia J Conrod, Benedicto Crespo-Facorro, Fabrice Crivello, Eveline A Crone, Liewe de Haan, Greig I de Zubicaray, Annabella Di Giorgio, Susanne Erk, Simon E Fisher, Barbara Franke, Thomas Frodl, David C Glahn, Dominik Grotegerd, Oliver Gruber, Patricia Gruner, Raquel E Gur, Ruben C Gur, Ben J Harrison, Sean N Hatton, Ian Hickie, Fleur M Howells, Hilleke E Hulshoff Pol, Chaim Huyser, Terry L Jernigan, Jiyang Jiang, John A Joska, Rene S Kahn, Andrew J Kalnin, Nicole A Kochan, Sanne Koops, Jonna Kuntsi, Jim Lagopoulos, Luisa Lazaro, Irina S Lebedeva, Christine Lochner, Nicholas G Martin, Bernard Mazoyer, Brenna C McDonald, Colm McDonald, Katie L McMahon, Tomohiro Nakao, Lars Nyberg, Fabrizio Piras, Maria J Portella, Jiang Qiu, Joshua L Roffman, Perminder S Sachdev, Nicole Sanford, Andrew J Saykin, Theodore D Satterthwaite, Sophia I Thomopolous, Carl M Sellgren, Kang Sim, Jordan W Smoller, Jair Soares, Iris E Sommer, Gianfranco Spalletta, Dan J Stein, Christian K Tamnes, Alexander S Tomyshev, Theo GM van Erp, Diana Tordesillas-Gutierrez, Julian N Trollor, Dennis van 't Ent, Odile A van den Heuvel, Neeltje EM van Haren, Daniela Vecchio, Dick J Veltman, Dongtao Wei, Henrik Walter, Yang Wang, Bernd Weber, Margaret J Wright, Wei Wen, Lars T Westlye, Lara M Wierenga, Paul M Thompson, Steven CR Williams, Sarah Medland, Mon-Ju Wu, Kevin Yu, Neda Jahanshad, and Sophia Frangou

Abstract

Background: Normative modeling is a statistical approach to quantify the degree to which a particular individual-level measure deviates from the pattern observed in a normative reference population. When applied to human brain morphometric measures it has the potential to inform about the significance of normative deviations for health and disease. Normative models can be implemented using a variety of algorithms that have not been systematically appraised. Methods: To address this gap, eight algorithms were compared in terms of performance and computational efficiency using brain regional morphometric data from 37,407 healthy individuals (53% female; aged 3-90 years) collated from 87 international MRI datasets. Performance was assessed with the mean absolute error (MAE) and computational efficiency was inferred from central processing unit (CPU) time. The algorithms evaluated were Ordinary Least Squares Regression (OLSR), Bayesian Linear Regression (BLR), Generalized Additive Models for Location, Scale, and Shape (GAMLSS), Parametric Lambda, Mu, Sigma (LMS), Gaussian Process Regression (GPR), Warped Bayesian Linear Regression (WBLG), Hierarchical Bayesian Regression (HBR), and Multivariable Fractional Polynomial Regression (MFPR). Model optimization involved testing nine covariate combinations pertaining to acquisition features, parcellation software versions, and global neuroimaging measures (i.e., total intracranial volume, mean cortical thickness, and mean cortical surface area). Findings: Statistical comparisons across models at PFDR

Published
2023

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