Author: "Penninx, Brenda W.J.H." / Database: OAIster - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"Penninx, Brenda W.J.H."' showing total 145 results

Start Over Author "Penninx, Brenda W.J.H." Database OAIster

145 results on '"Penninx, Brenda W.J.H."'

1. Psychosocial factors, health behaviors and risk of cancer incidence: Testing interaction and effect modification in an individual participant data meta-analysis

Author: Cardiovasculaire Epidemiologie, MS Medische Oncologie, Planetary Health & Exposoom, Cancer, Circulatory Health, Cardiovasculaire Epi Team 7a, Cardiometabolic Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, HAG Zorg, Cardiovasculaire Epi Team 5, Brain, Basten, Maartje, Pan, Kuan Yu, van Tuijl, Lonneke A., de Graeff, Alexander, Dekker, Joost, Hoogendoorn, Adriaan W., Lamers, Femke, Ranchor, Adelita V., Vermeulen, Roel, Portengen, Lützen, Voogd, Adri C., Abell, Jessica, Awadalla, Philip, Beekman, Aartjan T.F., Bjerkeset, Ottar, Boyd, Andy, Cui, Yunsong, Frank, Philipp, Galenkamp, Henrike, Garssen, Bert, Hellingman, Sean, Huisman, Martijn, Huss, Anke, Keats, Melanie R., Kok, Almar A.L., Krokstad, Steinar, van Leeuwen, Flora E., Luik, Annemarie I., Noisel, Nolwenn, Payette, Yves, Penninx, Brenda W.J.H., Rissanen, Ina, Roest, Annelieke M., Rosmalen, Judith G.M., Ruiter, Rikje, Schoevers, Robert A., Soave, David, Spaan, Mandy, Steptoe, Andrew, Stronks, Karien, Sund, Erik R., Sweeney, Ellen, Twait, Emma L., Teyhan, Alison, Verschuren, W. M.Monique, van der Willik, Kimberly D., Geerlings, Mirjam I., Cardiovasculaire Epidemiologie, MS Medische Oncologie, Planetary Health & Exposoom, Cancer, Circulatory Health, Cardiovasculaire Epi Team 7a, Cardiometabolic Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, HAG Zorg, Cardiovasculaire Epi Team 5, Brain, Basten, Maartje, Pan, Kuan Yu, van Tuijl, Lonneke A., de Graeff, Alexander, Dekker, Joost, Hoogendoorn, Adriaan W., Lamers, Femke, Ranchor, Adelita V., Vermeulen, Roel, Portengen, Lützen, Voogd, Adri C., Abell, Jessica, Awadalla, Philip, Beekman, Aartjan T.F., Bjerkeset, Ottar, Boyd, Andy, Cui, Yunsong, Frank, Philipp, Galenkamp, Henrike, Garssen, Bert, Hellingman, Sean, Huisman, Martijn, Huss, Anke, Keats, Melanie R., Kok, Almar A.L., Krokstad, Steinar, van Leeuwen, Flora E., Luik, Annemarie I., Noisel, Nolwenn, Payette, Yves, Penninx, Brenda W.J.H., Rissanen, Ina, Roest, Annelieke M., Rosmalen, Judith G.M., Ruiter, Rikje, Schoevers, Robert A., Soave, David, Spaan, Mandy, Steptoe, Andrew, Stronks, Karien, Sund, Erik R., Sweeney, Ellen, Twait, Emma L., Teyhan, Alison, Verschuren, W. M.Monique, van der Willik, Kimberly D., and Geerlings, Mirjam I.
Published: 2024

2. Childhood abuse v. neglect and risk for major psychiatric disorders

Author: AIOS Psychiatrie, Brain, Onderzoeksgroep 2, Onderzoeksgroep 11, Onderzoek, Psychiatrie_Medisch, Hart- en Vaatziekten Team A, Genetica, UMC Utrecht, Hersenen-Medisch 1, Alkema, Anne, Marchi, Mattia, Van Der Zaag, Jeroen A.J., Van Der Sluis, Daniëlle, Warrier, Varun, Ophoff, Roel A., Kahn, René S., Cahn, Wiepke, Hovens, Jacqueline G.F.M., Riese, Harriëtte, Scheepers, Floortje, Penninx, Brenda W.J.H., Cecil, Charlotte, Oldehinkel, Albertine J., Vinkers, Christiaan H., Boks, Marco P.M., Genetic Risk and Outcome of Psychosis (GROUP) Investigators, AIOS Psychiatrie, Brain, Onderzoeksgroep 2, Onderzoeksgroep 11, Onderzoek, Psychiatrie_Medisch, Hart- en Vaatziekten Team A, Genetica, UMC Utrecht, Hersenen-Medisch 1, Alkema, Anne, Marchi, Mattia, Van Der Zaag, Jeroen A.J., Van Der Sluis, Daniëlle, Warrier, Varun, Ophoff, Roel A., Kahn, René S., Cahn, Wiepke, Hovens, Jacqueline G.F.M., Riese, Harriëtte, Scheepers, Floortje, Penninx, Brenda W.J.H., Cecil, Charlotte, Oldehinkel, Albertine J., Vinkers, Christiaan H., Boks, Marco P.M., and Genetic Risk and Outcome of Psychosis (GROUP) Investigators
Published: 2024

3. The Mood and Resilience in Offspring (MARIO) project: a longitudinal cohort study among offspring of parents with and without a mood disorder

Author: Onderzoek, Brain, Vreeker, Annabel, Horsfall, Melany, Eikelenboom, Merijn, Beerthuizen, Annemerle, Bergink, Veerle, Boks, Marco P.M., Hartman, Catharina A., de Koning, Ricki, de Leeuw, Max, Maciejewski, Dominique F., Penninx, Brenda W.J.H., Hillegers, Manon H.J., Onderzoek, Brain, Vreeker, Annabel, Horsfall, Melany, Eikelenboom, Merijn, Beerthuizen, Annemerle, Bergink, Veerle, Boks, Marco P.M., Hartman, Catharina A., de Koning, Ricki, de Leeuw, Max, Maciejewski, Dominique F., Penninx, Brenda W.J.H., and Hillegers, Manon H.J.
Published: 2024

4. Exposome-Wide Association Study of Body Mass Index Using a Novel Meta-Analytical Approach for Random Forest Models

Author: Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Planetary Health & Exposoom, Cancer, Ohanyan, Haykanush, van de Wiel, Mark, Portengen, Lützen, Wagtendonk, Alfred, Den Braver, Nicolette R., de Jong, Trynke R., Verschuren, Monique, van den Hurk, Katja, Stronks, Karien, van Charante, Eric Moll, van Schoor, Natasja M., Stehouwer, Coen D.A., Wesselius, Anke, Koster, Annemarie, Have, Margreet Ten, Penninx, Brenda W.J.H., van Wier, Marieke F., Motoc, Irina, Oldehinkel, Albertine J., Willemsen, Gonneke, Boomsma, Dorret I., Beenackers, Mariëlle A., Huss, Anke, van Boxtel, Martin, Hoek, Gerard, Beulens, Joline W.J., Vermeulen, Roel, Lakerveld, Jeroen, Cardiometabolic Health, Circulatory Health, JC onderzoeksprogramma Cardiovascular Health, Planetary Health & Exposoom, Cancer, Ohanyan, Haykanush, van de Wiel, Mark, Portengen, Lützen, Wagtendonk, Alfred, Den Braver, Nicolette R., de Jong, Trynke R., Verschuren, Monique, van den Hurk, Katja, Stronks, Karien, van Charante, Eric Moll, van Schoor, Natasja M., Stehouwer, Coen D.A., Wesselius, Anke, Koster, Annemarie, Have, Margreet Ten, Penninx, Brenda W.J.H., van Wier, Marieke F., Motoc, Irina, Oldehinkel, Albertine J., Willemsen, Gonneke, Boomsma, Dorret I., Beenackers, Mariëlle A., Huss, Anke, van Boxtel, Martin, Hoek, Gerard, Beulens, Joline W.J., Vermeulen, Roel, and Lakerveld, Jeroen
Published: 2024

5. The aperiodic exponent of neural activity varies with vigilance state in mice and men

Author: Onderzoeksgroep 9, Brain, Østergaard, Freja Gam, Penninx, Brenda W.J.H., Das, Neetha, Arango, Celso, van der Wee, Nic, Winter-Van Rossum, Inge, Ayuso-Mateos, Jose Luis, Dawson, Gerard R., Marston, Hugh, Kas, Martien J.H., Onderzoeksgroep 9, Brain, Østergaard, Freja Gam, Penninx, Brenda W.J.H., Das, Neetha, Arango, Celso, van der Wee, Nic, Winter-Van Rossum, Inge, Ayuso-Mateos, Jose Luis, Dawson, Gerard R., Marston, Hugh, and Kas, Martien J.H.
Published: 2024

6. Exposome-Wide Association Study of Body Mass Index Using a Novel Meta-Analytical Approach for Random Forest Models

Author: Ohanyan, Haykanush, van de Wiel, Mark, Portengen, Lützen, Wagtendonk, Alfred, den Braver, Nicolette R., de Jong, Trynke R., Verschuren, Monique, van den Hurk, Katja, Stronks, Karien, Moll van Charante, Eric, van Schoor, Natasja M., Stehouwer, Coen D.A., Wesselius, Anke, Koster, Annemarie, Ten Have, Margreet, Penninx, Brenda W.J.H., van Wier, Marieke F., Motoc, Irina, Oldehinkel, Albertine J., Willemsen, Gonneke, Boomsma, Dorret I., Beenackers, Mariëlle A., Huss, Anke, van Boxtel, Martin, Hoek, Gerard, Beulens, Joline W.J., Vermeulen, Roel, Lakerveld, Jeroen, Ohanyan, Haykanush, van de Wiel, Mark, Portengen, Lützen, Wagtendonk, Alfred, den Braver, Nicolette R., de Jong, Trynke R., Verschuren, Monique, van den Hurk, Katja, Stronks, Karien, Moll van Charante, Eric, van Schoor, Natasja M., Stehouwer, Coen D.A., Wesselius, Anke, Koster, Annemarie, Ten Have, Margreet, Penninx, Brenda W.J.H., van Wier, Marieke F., Motoc, Irina, Oldehinkel, Albertine J., Willemsen, Gonneke, Boomsma, Dorret I., Beenackers, Mariëlle A., Huss, Anke, van Boxtel, Martin, Hoek, Gerard, Beulens, Joline W.J., Vermeulen, Roel, and Lakerveld, Jeroen
Abstract: BACKGROUND: Overweight and obesity impose a considerable individual and social burden, and the urban environments might encompass factors that contribute to obesity. Nevertheless, there is a scarcity of research that takes into account the simultaneous interaction of multiple environmental factors. OBJECTIVES: Our objective was to perform an exposome-wide association study of body mass index (BMI) in a multicohort setting of 15 studies. METHODS: Studies were affiliated with the Dutch Geoscience and Health Cohort Consortium (GECCO), had different population sizes (688–141,825), and covered the entire Netherlands. Ten studies contained general population samples, others focused on specific populations including people with diabetes or impaired hearing. BMI was calculated from self-reported or measured height and weight. Associations with 69 residential neighborhood environmental factors (air pollution, noise, temperature, neighborhood socioeconomic and demographic factors, food environment, drivability, and walkability) were explored. Random forest (RF) regression addressed potential nonlinear and nonadditive associations. In the absence of formal methods for multimodel inference for RF, a rank aggregation-based meta-analytic strategy was used to summarize the results across the studies. RESULTS: Six exposures were associated with BMI: five indicating neighborhood economic or social environments (average home values, percentage of high-income residents, average income, livability score, share of single residents) and one indicating the physical activity environment (walkability in 5-km buffer area). Living in high-income neighborhoods and neighborhoods with higher livability scores was associated with lower BMI. Nonlinear associations were observed with neighborhood home values in all studies. Lower neighborhood home values were associated with higher BMI scores but only for values up to e300,000. The directions of associations were less consistent for walkability
Published: 2024

7. Genomics Research of Lifetime Depression in the Netherlands : The BIObanks Netherlands Internet Collaboration (BIONIC) Project

Author: Huider, Floris, Milaneschi, Yuri, Hottenga, Jouke Jan, Bot, Mariska, Rietman, Liset, Kok, Almar A.L., Galesloot, Tessel E., T' Hart, Leen M., Rutters, Femke, Blom, Marieke T., Rhebergen, Didi, Visser, Marjolein, Brouwer, Ingeborg, Feskens, Edith, Hartman, Catharina A., Oldehinkel, Albertine J., De Geus, Eco J.C., Kiemeney, Lambertus A., Huisman, Martijn, Picavet, Susan J., Verschuren, Monique, Van Loo, Hanna M., Penninx, Brenda W.J.H., Boomsma, Dorret I., Huider, Floris, Milaneschi, Yuri, Hottenga, Jouke Jan, Bot, Mariska, Rietman, Liset, Kok, Almar A.L., Galesloot, Tessel E., T' Hart, Leen M., Rutters, Femke, Blom, Marieke T., Rhebergen, Didi, Visser, Marjolein, Brouwer, Ingeborg, Feskens, Edith, Hartman, Catharina A., Oldehinkel, Albertine J., De Geus, Eco J.C., Kiemeney, Lambertus A., Huisman, Martijn, Picavet, Susan J., Verschuren, Monique, Van Loo, Hanna M., Penninx, Brenda W.J.H., and Boomsma, Dorret I.
Abstract: In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping. For standardized phenotyping we developed the LIDAS (LIfetime Depression Assessment Survey), which then was used to measure MDD in 11 Dutch cohorts. Data from these cohorts were combined with diagnostic interview depression data from 5 clinical cohorts to create a dataset of N = 29,650 lifetime MDD cases (22%) meeting DSM-5 criteria and 94,300 screened controls. In addition, genomewide genotype data from the cohorts were assembled into a genomewide association study (GWAS) dataset of N = 66,684 Dutch individuals (25.3% cases). Phenotype data include DSM-5-based MDD diagnoses, sociodemographic variables, information on lifestyle and BMI, characteristics of depressive symptoms and episodes, and psychiatric diagnosis and treatment history. We describe the establishment and harmonization of the BIONIC phenotype and GWAS datasets and provide an overview of the available information and sample characteristics. Our next step is the GWAS of lifetime MDD in the Netherlands, with future plans including fine-grained genetic analyses of depression characteristics, international collaborations and multi-omics studies.
Published: 2024

8. Digital behavioural signatures reveal trans-diagnostic clusters of Schizophrenia and Alzheimer's disease patients

Author: Kas, Martien J., Jongs, Niels, Mennes, M.J.J., Penninx, Brenda W.J.H., Arango, Celso, Wee, Nic van der, Beckmann, C.F., Sommer, B., Marston, Hugh M., Kas, Martien J., Jongs, Niels, Mennes, M.J.J., Penninx, Brenda W.J.H., Arango, Celso, Wee, Nic van der, Beckmann, C.F., Sommer, B., and Marston, Hugh M.
Abstract: Item does not contain fulltext
Published: 2024

9. Long-term glucocorticoids in relation to the metabolic syndrome and cardiovascular disease:A systematic review and meta-analysis

Author: Kuckuck, Susanne, Lengton, Robin, Boon, Mariëtte R., Boersma, Eric, Penninx, Brenda W.J.H., Kavousi, Maryam, van Rossum, Elisabeth F.C., Kuckuck, Susanne, Lengton, Robin, Boon, Mariëtte R., Boersma, Eric, Penninx, Brenda W.J.H., Kavousi, Maryam, and van Rossum, Elisabeth F.C.
Abstract: The striking link of Cushing's syndrome with the metabolic syndrome (MetS) and cardiovascular disease (CVD) suggests that long-term exposure to extremely high cortisol levels catalyzes cardiometabolic deterioration. However, it remained unclear whether the findings from the extreme glucocorticoid overabundance observed in Cushing's syndrome could be translated into more subtle variations in long-term glucocorticoid levels among the general population, for example, due to chronic stress. Here, we performed a systematic review (PROSPERO: CRD42023425541) of evidence regarding the role of subtle variations in long-term biological stress, measured as levels of scalp hair cortisol (HairF) and cortisone (HairE), in the context of MetS and CVD in adults. We also performed a meta-analysis on the cross-sectional difference in HairF levels between individuals with versus without CVD. Seven studies were included regarding MetS, sixteen regarding CVD, and one regarding both. Most articles indicated a strong, consistent cross-sectional association of higher HairF and HairE levels with CVD, which was confirmed by our meta-analysis for HairF (eight studies, SMD = 0.48, 95% confidence intervals [CIs]: 0.16–0.79, p = 0.0095). Moreover, these relationships appear largely independent of standard risk factors. Age seems relevant as the effect seems stronger in younger individuals. Results regarding the associations of HairF and HairE with MetS were inconsistent. Altogether, long-term biological stress, measured as HairF and HairE, is associated with the presence of CVD, and less consistently with MetS. Prospective studies need to evaluate the directionality of this relationship and determine whether HairF and HairE can be used in addition to standard risk factors in predicting future cardiometabolic deterioration.
Published: 2024

10. Psychosocial factors, health behaviors and risk of cancer incidence:Testing interaction and effect modification in an individual participant data meta-analysis

Author: Basten, Maartje, Pan, Kuan Yu, van Tuijl, Lonneke A., de Graeff, Alexander, Dekker, Joost, Hoogendoorn, Adriaan W., Lamers, Femke, Ranchor, Adelita V., Vermeulen, Roel, Portengen, Lützen, Voogd, Adri C., Abell, Jessica, Awadalla, Philip, Beekman, Aartjan T.F., Bjerkeset, Ottar, Boyd, Andy, Cui, Yunsong, Frank, Philipp, Galenkamp, Henrike, Garssen, Bert, Hellingman, Sean, Huisman, Martijn, Huss, Anke, Keats, Melanie R., Kok, Almar A.L., Krokstad, Steinar, van Leeuwen, Flora E., Luik, Annemarie I., Noisel, Nolwenn, Payette, Yves, Penninx, Brenda W.J.H., Rissanen, Ina, Roest, Annelieke M., Rosmalen, Judith G.M., Ruiter, Rikje, Schoevers, Robert A., Soave, David, Spaan, Mandy, Steptoe, Andrew, Stronks, Karien, Sund, Erik R., Sweeney, Ellen, Twait, Emma L., Teyhan, Alison, Verschuren, W. M.Monique, van der Willik, Kimberly D., Geerlings, Mirjam I., Basten, Maartje, Pan, Kuan Yu, van Tuijl, Lonneke A., de Graeff, Alexander, Dekker, Joost, Hoogendoorn, Adriaan W., Lamers, Femke, Ranchor, Adelita V., Vermeulen, Roel, Portengen, Lützen, Voogd, Adri C., Abell, Jessica, Awadalla, Philip, Beekman, Aartjan T.F., Bjerkeset, Ottar, Boyd, Andy, Cui, Yunsong, Frank, Philipp, Galenkamp, Henrike, Garssen, Bert, Hellingman, Sean, Huisman, Martijn, Huss, Anke, Keats, Melanie R., Kok, Almar A.L., Krokstad, Steinar, van Leeuwen, Flora E., Luik, Annemarie I., Noisel, Nolwenn, Payette, Yves, Penninx, Brenda W.J.H., Rissanen, Ina, Roest, Annelieke M., Rosmalen, Judith G.M., Ruiter, Rikje, Schoevers, Robert A., Soave, David, Spaan, Mandy, Steptoe, Andrew, Stronks, Karien, Sund, Erik R., Sweeney, Ellen, Twait, Emma L., Teyhan, Alison, Verschuren, W. M.Monique, van der Willik, Kimberly D., and Geerlings, Mirjam I.
Abstract: Depression, anxiety and other psychosocial factors are hypothesized to be involved in cancer development. We examined whether psychosocial factors interact with or modify the effects of health behaviors, such as smoking and alcohol use, in relation to cancer incidence. Two-stage individual participant data meta-analyses were performed based on 22 cohorts of the PSYchosocial factors and CAncer (PSY-CA) study. We examined nine psychosocial factors (depression diagnosis, depression symptoms, anxiety diagnosis, anxiety symptoms, perceived social support, loss events, general distress, neuroticism, relationship status), seven health behaviors/behavior-related factors (smoking, alcohol use, physical activity, body mass index, sedentary behavior, sleep quality, sleep duration) and seven cancer outcomes (overall cancer, smoking-related, alcohol-related, breast, lung, prostate, colorectal). Effects of the psychosocial factor, health behavior and their product term on cancer incidence were estimated using Cox regression. We pooled cohort-specific estimates using multivariate random-effects meta-analyses. Additive and multiplicative interaction/effect modification was examined. This study involved 437,827 participants, 36,961 incident cancer diagnoses, and 4,749,481 person years of follow-up. Out of 744 combinations of psychosocial factors, health behaviors, and cancer outcomes, we found no evidence of interaction. Effect modification was found for some combinations, but there were no clear patterns for any particular factors or outcomes involved. In this first large study to systematically examine potential interaction and effect modification, we found no evidence for psychosocial factors to interact with or modify health behaviors in relation to cancer incidence. The behavioral risk profile for cancer incidence is similar in people with and without psychosocial stress.
Published: 2024

11. The role of explicit and implicit self-esteem in the relationship between childhood trauma and adult depression and anxiety

Author: Leerstoel Boelen, Trauma and Grief, Sub General Pharmacology, Gathier, Anouk W., van Tuijl, Lonneke A., Penninx, Brenda W.J.H., de Jong, Peter J., van Oppen, Patricia C., Vinkers, Christiaan H., Verhoeven, Josine E., Leerstoel Boelen, Trauma and Grief, Sub General Pharmacology, Gathier, Anouk W., van Tuijl, Lonneke A., Penninx, Brenda W.J.H., de Jong, Peter J., van Oppen, Patricia C., Vinkers, Christiaan H., and Verhoeven, Josine E.
Published: 2024

12. The Mood and Resilience in Offspring (MARIO) project:a longitudinal cohort study among offspring of parents with and without a mood disorder

Author: Vreeker, Annabel, Horsfall, Melany, Eikelenboom, Merijn, Beerthuizen, Annemerle, Bergink, Veerle, Boks, Marco P.M., Hartman, Catharina A., de Koning, Ricki, de Leeuw, Max, Maciejewski, Dominique F., Penninx, Brenda W.J.H., Hillegers, Manon H.J., Vreeker, Annabel, Horsfall, Melany, Eikelenboom, Merijn, Beerthuizen, Annemerle, Bergink, Veerle, Boks, Marco P.M., Hartman, Catharina A., de Koning, Ricki, de Leeuw, Max, Maciejewski, Dominique F., Penninx, Brenda W.J.H., and Hillegers, Manon H.J.
Abstract: Background:One of the most robust risk factors for developing a mood disorder is having a parent with a mood disorder. Unfortunately, mechanisms explaining the transmission of mood disorders from one generation to the next remain largely elusive. Since timely intervention is associated with a better outcome and prognosis, early detection of intergenerational transmission of mood disorders is of paramount importance. Here, we describe the design of the Mood and Resilience in Offspring (MARIO) cohort study in which we investigate: 1. differences in clinical, biological and environmental (e.g., psychosocial factors, substance use or stressful life events) risk and resilience factors in children of parents with and without mood disorders, and 2. mechanisms of intergenerational transmission of mood disorders via clinical, biological and environmental risk and resilience factors. Methods: MARIO is an observational, longitudinal cohort study that aims to include 450 offspring of parents with a mood disorder (uni- or bipolar mood disorders) and 100-150 offspring of parents without a mood disorder aged 10-25 years. Power analyses indicate that this sample size is sufficient to detect small to medium sized effects. Offspring are recruited via existing Dutch studies involving patients with a mood disorder and healthy controls, for which detailed clinical, environmental and biological data of the index-parent (i.e., the initially identified parent with or without a mood disorder) is available. Over a period of three years, four assessments will take place, in which extensive clinical, biological and environmental data and data on risk and resilience are collected through e.g., blood sampling, face-to-face interviews, online questionnaires, actigraphy and Experience Sampling Method assessment. For co-parents, information on demographics, mental disorder status and a DNA-sample are collected.Discussion: The MARIO cohort s
Published: 2024

13. Genome-wide characterization of circulating metabolic biomarkers

Author: Karjalainen, Minna K., Karthikeyan, Savita, Oliver-Williams, Clare, Sliz, Eeva, Allara, Elias, Fung, Wing Tung, Surendran, Praveen, Zhang, Weihua, Jousilahti, Pekka, Kristiansson, Kati, Salomaa, Veikko, Goodwin, Matt, Hughes, David A., Boehnke, Michael, Fernandes Silva, Lilian, Yin, Xianyong, Mahajan, Anubha, Neville, Matt J., van Zuydam, Natalie R., de Mutsert, Renée, Li-Gao, Ruifang, Mook-Kanamori, Dennis O., Demirkan, Ayse, Liu, Jun, Noordam, Raymond, Trompet, Stella, Chen, Zhengming, Kartsonaki, Christiana, Li, Liming, Lin, Kuang, Hagenbeek, Fiona A., Hottenga, Jouke Jan, Pool, René, Ikram, M. Arfan, van Meurs, Joyce, Haller, Toomas, Milaneschi, Yuri, Kähönen, Mika, Mishra, Pashupati P., Joshi, Peter K., Macdonald-Dunlop, Erin, Mangino, Massimo, Zierer, Jonas, Acar, Ilhan E., Hoyng, Carel B., Lechanteur, Yara T.E., Franke, Lude, Kurilshikov, Alexander, Zhernakova, Alexandra, Beekman, Marian, van den Akker, Erik B., Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Gieger, Christian, Waldenberger, Melanie, Asselbergs, Folkert W., Hayward, Caroline, Fu, Jingyuan, den Hollander, Anneke I., Menni, Cristina, Spector, Tim D., Wilson, James F., Lehtimäki, Terho, Raitakari, Olli T., Penninx, Brenda W.J.H., Esko, Tonu, Walters, Robin G., Jukema, J. Wouter, Sattar, Naveed, Ghanbari, Mohsen, Willems van Dijk, Ko, Karpe, Fredrik, McCarthy, Mark I., Laakso, Markku, Järvelin, Marjo Riitta, Timpson, Nicholas J., Perola, Markus, Kooner, Jaspal S., Chambers, John C., van Duijn, Cornelia, Slagboom, P. Eline, Boomsma, Dorret I., Danesh, John, Ala-Korpela, Mika, Butterworth, Adam S., Kettunen, Johannes, Karjalainen, Minna K., Karthikeyan, Savita, Oliver-Williams, Clare, Sliz, Eeva, Allara, Elias, Fung, Wing Tung, Surendran, Praveen, Zhang, Weihua, Jousilahti, Pekka, Kristiansson, Kati, Salomaa, Veikko, Goodwin, Matt, Hughes, David A., Boehnke, Michael, Fernandes Silva, Lilian, Yin, Xianyong, Mahajan, Anubha, Neville, Matt J., van Zuydam, Natalie R., de Mutsert, Renée, Li-Gao, Ruifang, Mook-Kanamori, Dennis O., Demirkan, Ayse, Liu, Jun, Noordam, Raymond, Trompet, Stella, Chen, Zhengming, Kartsonaki, Christiana, Li, Liming, Lin, Kuang, Hagenbeek, Fiona A., Hottenga, Jouke Jan, Pool, René, Ikram, M. Arfan, van Meurs, Joyce, Haller, Toomas, Milaneschi, Yuri, Kähönen, Mika, Mishra, Pashupati P., Joshi, Peter K., Macdonald-Dunlop, Erin, Mangino, Massimo, Zierer, Jonas, Acar, Ilhan E., Hoyng, Carel B., Lechanteur, Yara T.E., Franke, Lude, Kurilshikov, Alexander, Zhernakova, Alexandra, Beekman, Marian, van den Akker, Erik B., Kolcic, Ivana, Polasek, Ozren, Rudan, Igor, Gieger, Christian, Waldenberger, Melanie, Asselbergs, Folkert W., Hayward, Caroline, Fu, Jingyuan, den Hollander, Anneke I., Menni, Cristina, Spector, Tim D., Wilson, James F., Lehtimäki, Terho, Raitakari, Olli T., Penninx, Brenda W.J.H., Esko, Tonu, Walters, Robin G., Jukema, J. Wouter, Sattar, Naveed, Ghanbari, Mohsen, Willems van Dijk, Ko, Karpe, Fredrik, McCarthy, Mark I., Laakso, Markku, Järvelin, Marjo Riitta, Timpson, Nicholas J., Perola, Markus, Kooner, Jaspal S., Chambers, John C., van Duijn, Cornelia, Slagboom, P. Eline, Boomsma, Dorret I., Danesh, John, Ala-Korpela, Mika, Butterworth, Adam S., and Kettunen, Johannes
Abstract: Genome-wide association analyses using high-throughput metabolomics platforms have led to novel insights into the biology of human metabolism1–7. This detailed knowledge of the genetic determinants of systemic metabolism has been pivotal for uncovering how genetic pathways influence biological mechanisms and complex diseases8–11. Here we present a genome-wide association study for 233 circulating metabolic traits quantified by nuclear magnetic resonance spectroscopy in up to 136,016 participants from 33 cohorts. We identify more than 400 independent loci and assign probable causal genes at two-thirds of these using manual curation of plausible biological candidates. We highlight the importance of sample and participant characteristics that can have significant effects on genetic associations. We use detailed metabolic profiling of lipoprotein- and lipid-associated variants to better characterize how known lipid loci and novel loci affect lipoprotein metabolism at a granular level. We demonstrate the translational utility of comprehensively phenotyped molecular data, characterizing the metabolic associations of intrahepatic cholestasis of pregnancy. Finally, we observe substantial genetic pleiotropy for multiple metabolic pathways and illustrate the importance of careful instrument selection in Mendelian randomization analysis, revealing a putative causal relationship between acetone and hypertension. Our publicly available results provide a foundational resource for the community to examine the role of metabolism across diverse diseases.
Published: 2024

14. Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan : a pooled analysis in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Background: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. Methods: We included 3838 participants aged 18–90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. Results: High alcohol use was associated with lower hippocampal volume (r = −0.10, p = 0.021), and overweight/obesity with lower total GMV (r = −0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = −0.08, p = 0.001), but not hippocampal volume (r = −0.01, p = 0.625). Conclusions: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.
Published: 2023
Full Text: View/download PDF

15. Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan : a pooled analysis in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Background: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. Methods: We included 3838 participants aged 18–90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. Results: High alcohol use was associated with lower hippocampal volume (r = −0.10, p = 0.021), and overweight/obesity with lower total GMV (r = −0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = −0.08, p = 0.001), but not hippocampal volume (r = −0.01, p = 0.625). Conclusions: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.
Published: 2023
Full Text: View/download PDF

16. Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan : a pooled analysis in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Background: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. Methods: We included 3838 participants aged 18–90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. Results: High alcohol use was associated with lower hippocampal volume (r = −0.10, p = 0.021), and overweight/obesity with lower total GMV (r = −0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = −0.08, p = 0.001), but not hippocampal volume (r = −0.01, p = 0.625). Conclusions: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.
Published: 2023
Full Text: View/download PDF

17. Genome-wide analysis identifies genetic effects on reproductive success and ongoing natural selection at the FADS locus

Author: Mathieson, Iain, Day, Felix R., Barban, Nicola, Boomsma, Dorret I., de Geus, Eco J.C., Hottenga, Jouke Jan, Jansen, Rick, Mbarek, Hamdi, Penninx, Brenda W.J.H., Willemsen, Gonneke, Snieder, Harold, den Hoed, Marcel, Ong, Ken K., Mills, Melinda C., Perry, John R.B., eQTLGen Consortium, BIOS Consortium, FinnGen Study, LifeLines Cohort Study, Mathieson, Iain, Day, Felix R., Barban, Nicola, Boomsma, Dorret I., de Geus, Eco J.C., Hottenga, Jouke Jan, Jansen, Rick, Mbarek, Hamdi, Penninx, Brenda W.J.H., Willemsen, Gonneke, Snieder, Harold, den Hoed, Marcel, Ong, Ken K., Mills, Melinda C., Perry, John R.B., eQTLGen Consortium, BIOS Consortium, FinnGen Study, and LifeLines Cohort Study
Abstract: Identifying genetic determinants of reproductive success may highlight mechanisms underlying fertility and identify alleles under present-day selection. Using data in 785,604 individuals of European ancestry, we identified 43 genomic loci associated with either number of children ever born (NEB) or childlessness. These loci span diverse aspects of reproductive biology, including puberty timing, age at first birth, sex hormone regulation, endometriosis and age at menopause. Missense variants in ARHGAP27 were associated with higher NEB but shorter reproductive lifespan, suggesting a trade-off at this locus between reproductive ageing and intensity. Other genes implicated by coding variants include PIK3IP1, ZFP82 and LRP4, and our results suggest a new role for the melanocortin 1 receptor (MC1R) in reproductive biology. As NEB is one component of evolutionary fitness, our identified associations indicate loci under present-day natural selection. Integration with data from historical selection scans highlighted an allele in the FADS1/2 gene locus that has been under selection for thousands of years and remains so today. Collectively, our findings demonstrate that a broad range of biological mechanisms contribute to reproductive success.
Published: 2023
Full Text: View/download PDF

18. Childhood abuse v. neglect and risk for major psychiatric disorders

Author: Alkema, Anne, Marchi, Mattia, Van Der Zaag, Jeroen A.J., Van Der Sluis, Daniëlle, Warrier, Varun, Ophoff, Roel A., Kahn, René S., Cahn, Wiepke, Hovens, Jacqueline G.F.M., Riese, Harriëtte, Scheepers, Floortje, Penninx, Brenda W.J.H., Cecil, Charlotte, Oldehinkel, Albertine J., Vinkers, Christiaan H., Boks, Marco P.M., Alizadeh, Behrooz Z., Van Amelsvoort, Therese, De Haane, Lieuwe, Schirmbeck, Frederike, Simons, Claudia J.P., Van Os, Jim, Veling, Wim, Alkema, Anne, Marchi, Mattia, Van Der Zaag, Jeroen A.J., Van Der Sluis, Daniëlle, Warrier, Varun, Ophoff, Roel A., Kahn, René S., Cahn, Wiepke, Hovens, Jacqueline G.F.M., Riese, Harriëtte, Scheepers, Floortje, Penninx, Brenda W.J.H., Cecil, Charlotte, Oldehinkel, Albertine J., Vinkers, Christiaan H., Boks, Marco P.M., Alizadeh, Behrooz Z., Van Amelsvoort, Therese, De Haane, Lieuwe, Schirmbeck, Frederike, Simons, Claudia J.P., Van Os, Jim, and Veling, Wim
Abstract: Background:Childhood maltreatment (CM) is a strong risk factor for psychiatric disorders but serves in its current definitions as an umbrella for various fundamentally different childhood experiences. As first step toward a more refined analysis of the impact of CM, our objective is to revisit the relation of abuse and neglect, major subtypes of CM, with symptoms across disorders. Methods:Three longitudinal studies of major depressive disorder (MDD, N = 1240), bipolar disorder (BD, N = 1339), and schizophrenia (SCZ, N = 577), each including controls (N = 881), were analyzed. Multivariate regression models were used to examine the relation between exposure to abuse, neglect, or their combination to the odds for MDD, BD, SCZ, and symptoms across disorders. Bidirectional Mendelian randomization (MR) was used to probe causality, using genetic instruments of abuse and neglect derived from UK Biobank data (N = 143 473). Results:Abuse was the stronger risk factor for SCZ (OR 3.51, 95% CI 2.17-5.67) and neglect for BD (OR 2.69, 95% CI 2.09-3.46). Combined CM was related to increased risk exceeding additive effects of abuse and neglect for MDD (RERI = 1.4) and BD (RERI = 1.1). Across disorders, abuse was associated with hallucinations (OR 2.16, 95% CI 1.55-3.01) and suicide attempts (OR 2.16, 95% CI 1.55-3.01) whereas neglect was associated with agitation (OR 1.24, 95% CI 1.02-1.51) and reduced need for sleep (OR 1.64, 95% CI 1.08-2.48). MR analyses were consistent with a bidirectional causal effect of abuse with SCZ (IVWforward = 0.13, 95% CI 0.01-0.24). Conclusion:Childhood abuse and neglect are associated with different risks to psychiatric symptoms and disorders. Unraveling the origin of these differences may advance understanding of disease etiology and ultimately facilitate development of improved personalized treatment strategies.
Published: 2023

19. Depression, anxiety, and the risk of cancer:An individual participant data meta-analysis

Author: van Tuijl, Lonneke A., Basten, Maartje, Pan, Kuan Yu, Vermeulen, Roel, Portengen, Lützen, de Graeff, Alexander, Dekker, Joost, Geerlings, Mirjam I., Hoogendoorn, Adriaan, Lamers, Femke, Voogd, Adri C., Abell, Jessica, Awadalla, Philip, Beekman, Aartjan T.F., Bjerkeset, Ottar, Boyd, Andy, Cui, Yunsong, Frank, Philipp, Galenkamp, Henrike, Garssen, Bert, Hellingman, Sean, Huisman, Martijn, Huss, Anke, de Jong, Trynke R., Keats, Melanie R., Kok, Almar A.L., Krokstad, Steinar, van Leeuwen, Flora E., Luik, Annemarie I., Noisel, Nolwenn, Onland-Moret, N. Charlotte, Payette, Yves, Penninx, Brenda W.J.H., Rissanen, Ina, Roest, Annelieke M., Ruiter, Rikje, Schoevers, Robert A., Soave, David, Spaan, Mandy, Steptoe, Andrew, Stronks, Karien, Sund, Erik R., Sweeney, Ellen, Twait, Emma L., Teyhan, Alison, Verschuren, W. M.Monique, van der Willik, Kimberly D., Rosmalen, Judith G.M., Ranchor, Adelita V., van Tuijl, Lonneke A., Basten, Maartje, Pan, Kuan Yu, Vermeulen, Roel, Portengen, Lützen, de Graeff, Alexander, Dekker, Joost, Geerlings, Mirjam I., Hoogendoorn, Adriaan, Lamers, Femke, Voogd, Adri C., Abell, Jessica, Awadalla, Philip, Beekman, Aartjan T.F., Bjerkeset, Ottar, Boyd, Andy, Cui, Yunsong, Frank, Philipp, Galenkamp, Henrike, Garssen, Bert, Hellingman, Sean, Huisman, Martijn, Huss, Anke, de Jong, Trynke R., Keats, Melanie R., Kok, Almar A.L., Krokstad, Steinar, van Leeuwen, Flora E., Luik, Annemarie I., Noisel, Nolwenn, Onland-Moret, N. Charlotte, Payette, Yves, Penninx, Brenda W.J.H., Rissanen, Ina, Roest, Annelieke M., Ruiter, Rikje, Schoevers, Robert A., Soave, David, Spaan, Mandy, Steptoe, Andrew, Stronks, Karien, Sund, Erik R., Sweeney, Ellen, Twait, Emma L., Teyhan, Alison, Verschuren, W. M.Monique, van der Willik, Kimberly D., Rosmalen, Judith G.M., and Ranchor, Adelita V.
Abstract: Background: Depression and anxiety have long been hypothesized to be related to an increased cancer risk. Despite the great amount of research that has been conducted, findings are inconclusive. To provide a stronger basis for addressing the associations between depression, anxiety, and the incidence of various cancer types (overall, breast, lung, prostate, colorectal, alcohol-related, and smoking-related cancers), individual participant data (IPD) meta-analyses were performed within the Psychosocial Factors and Cancer Incidence (PSY-CA) consortium. Methods: The PSY-CA consortium includes data from 18 cohorts with measures of depression or anxiety (up to N = 319,613; cancer incidences, 25,803; person-years of follow-up, 3,254,714). Both symptoms and a diagnosis of depression and anxiety were examined as predictors of future cancer risk. Two-stage IPD meta-analyses were run, first by using Cox regression models in each cohort (stage 1), and then by aggregating the results in random-effects meta-analyses (stage 2). Results: No associations were found between depression or anxiety and overall, breast, prostate, colorectal, and alcohol-related cancers. Depression and anxiety (symptoms and diagnoses) were associated with the incidence of lung cancer and smoking-related cancers (hazard ratios [HRs], 1.06–1.60). However, these associations were substantially attenuated when additionally adjusting for known risk factors including smoking, alcohol use, and body mass index (HRs, 1.04–1.23). Conclusions: Depression and anxiety are not related to increased risk for most cancer outcomes, except for lung and smoking-related cancers. This study shows that key covariates are likely to explain the relationship between depression, anxiety, and lung and smoking-related cancers. Preregistration number: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=157677.
Published: 2023

20. A multivariate genome-wide association study of psycho-cardiometabolic multimorbidity

Author: Baltramonaityte, Vilte, Pingault, Jean Baptiste, Cecil, Charlotte A.M., Choudhary, Priyanka, Järvelin, Marjo Riitta, Penninx, Brenda W.J.H., Felix, Janine, Sebert, Sylvain, Milaneschi, Yuri, Walton, Esther, Baltramonaityte, Vilte, Pingault, Jean Baptiste, Cecil, Charlotte A.M., Choudhary, Priyanka, Järvelin, Marjo Riitta, Penninx, Brenda W.J.H., Felix, Janine, Sebert, Sylvain, Milaneschi, Yuri, and Walton, Esther
Abstract: Coronary artery disease (CAD), type 2 diabetes (T2D) and depression are among the leading causes of chronic morbidity and mortality worldwide. Epidemiological studies indicate a substantial degree of multimorbidity, which may be explained by shared genetic influences. However, research exploring the presence of pleiotropic variants and genes common to CAD, T2D and depression is lacking. The present study aimed to identify genetic variants with effects on cross-trait liability to psycho-cardiometabolic diseases. We used genomic structural equation modelling to perform a multivariate genome-wide association study of multimorbidity (Neffective = 562,507), using summary statistics from univariate genome-wide association studies for CAD, T2D and major depression. CAD was moderately genetically correlated with T2D (rg = 0.39, P = 2e-34) and weakly correlated with depression (rg = 0.13, P = 3e-6). Depression was weakly correlated with T2D (rg = 0.15, P = 4e-15). The latent multimorbidity factor explained the largest proportion of variance in T2D (45%), followed by CAD (35%) and depression (5%). We identified 11 independent SNPs associated with multimorbidity and 18 putative multimorbidity-associated genes. We observed enrichment in immune and inflammatory pathways. A greater polygenic risk score for multimorbidity in the UK Biobank (N = 306,734) was associated with the co-occurrence of CAD, T2D and depression (OR per standard deviation = 1.91, 95% CI = 1.74–2.10, relative to the healthy group), validating this latent multimorbidity factor. Mendelian randomization analyses suggested potentially causal effects of BMI, body fat percentage, LDL cholesterol, total cholesterol, fasting insulin, income, insomnia, and childhood maltreatment. These findings advance our understanding of multimorbidity suggesting common genetic pathways.
Published: 2023

21. Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan : a pooled analysis in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Background: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. Methods: We included 3838 participants aged 18–90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. Results: High alcohol use was associated with lower hippocampal volume (r = −0.10, p = 0.021), and overweight/obesity with lower total GMV (r = −0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = −0.08, p = 0.001), but not hippocampal volume (r = −0.01, p = 0.625). Conclusions: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.
Published: 2023
Full Text: View/download PDF

22. Lifestyle-related risk factors and their cumulative associations with hippocampal and total grey matter volume across the adult lifespan : a pooled analysis in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Boraxbekk, Carl-Johan, Demnitz, Naiara, Drevon, Christian A., Fjell, Anders M., Lindenberger, Ulman, Madsen, Kathrine Skak, Nyberg, Lars, Topiwala, Anya, Walhovd, Kristine B., Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Background: Lifestyle-related risk factors, such as obesity, physical inactivity, short sleep, smoking and alcohol use, have been associated with low hippocampal and total grey matter volumes (GMV). However, these risk factors have mostly been assessed as separate factors, leaving it unknown if variance explained by these factors is overlapping or additive. We investigated associations of five lifestyle-related factors separately and cumulatively with hippocampal and total GMV, pooled across eight European cohorts. Methods: We included 3838 participants aged 18–90 years from eight cohorts of the European Lifebrain consortium. Using individual person data, we performed cross-sectional meta-analyses on associations of presence of lifestyle-related risk factors separately (overweight/obesity, physical inactivity, short sleep, smoking, high alcohol use) as well as a cumulative unhealthy lifestyle score (counting the number of present lifestyle-related risk factors) with FreeSurfer-derived hippocampal volume and total GMV. Lifestyle-related risk factors were defined according to public health guidelines. Results: High alcohol use was associated with lower hippocampal volume (r = −0.10, p = 0.021), and overweight/obesity with lower total GMV (r = −0.09, p = 0.001). Other lifestyle-related risk factors were not significantly associated with hippocampal volume or GMV. The cumulative unhealthy lifestyle score was negatively associated with total GMV (r = −0.08, p = 0.001), but not hippocampal volume (r = −0.01, p = 0.625). Conclusions: This large pooled study confirmed the negative association of some lifestyle-related risk factors with hippocampal volume and GMV, although with small effect sizes. Lifestyle factors should not be seen in isolation as there is evidence that having multiple unhealthy lifestyle factors is associated with a linear reduction in overall brain volume.
Published: 2023
Full Text: View/download PDF

23. Depression, cardiometabolic disease, and their co-occurrence after childhood maltreatment:an individual participant data meta-analysis including over 200,000 participants

Author: Souama, Camille, Lamers, Femke, Milaneschi, Yuri, Vinkers, Christiaan H., Defina, Serena, Garvert, Linda, Stein, Frederike, Woofenden, Tom, Brosch, Katharina, Dannlowski, Udo, Galenkamp, Henrike, de Graaf, Ron, Jaddoe, Vincent W.V., Lok, Anja, van Rijn, Bas B., Völzke, Henry, Cecil, Charlotte A.M., Felix, Janine F., Grabe, Hans J., Kircher, Tilo, Lekadir, Karim, Have, Margreet ten, Walton, Esther, Penninx, Brenda W.J.H., Souama, Camille, Lamers, Femke, Milaneschi, Yuri, Vinkers, Christiaan H., Defina, Serena, Garvert, Linda, Stein, Frederike, Woofenden, Tom, Brosch, Katharina, Dannlowski, Udo, Galenkamp, Henrike, de Graaf, Ron, Jaddoe, Vincent W.V., Lok, Anja, van Rijn, Bas B., Völzke, Henry, Cecil, Charlotte A.M., Felix, Janine F., Grabe, Hans J., Kircher, Tilo, Lekadir, Karim, Have, Margreet ten, Walton, Esther, and Penninx, Brenda W.J.H.
Abstract: Background: Childhood maltreatment is associated with depression and cardiometabolic disease in adulthood. However, the relationships with these two diseases have so far only been evaluated in different samples and with different methodology. Thus, it remains unknown how the effect sizes magnitudes for depression and cardiometabolic disease compare with each other and whether childhood maltreatment is especially associated with the co-occurrence (“comorbidity”) of depression and cardiometabolic disease. This pooled analysis examined the association of childhood maltreatment with depression, cardiometabolic disease, and their comorbidity in adulthood. Methods: We carried out an individual participant data meta-analysis on 13 international observational studies (N = 217,929). Childhood maltreatment comprised self-reports of physical, emotional, and/or sexual abuse before 18 years. Presence of depression was established with clinical interviews or validated symptom scales and presence of cardiometabolic disease with self-reported diagnoses. In included studies, binomial and multinomial logistic regressions estimated sociodemographic-adjusted associations of childhood maltreatment with depression, cardiometabolic disease, and their comorbidity. We then additionally adjusted these associations for lifestyle factors (smoking status, alcohol consumption, and physical activity). Finally, random-effects models were used to pool these estimates across studies and examined differences in associations across sex and maltreatment types. Results: Childhood maltreatment was associated with progressively higher odds of cardiometabolic disease without depression (OR [95% CI] = 1.27 [1.18; 1.37]), depression without cardiometabolic disease (OR [95% CI] = 2.68 [2.39; 3.00]), and comorbidity between both conditions (OR [95% CI] = 3.04 [2.51; 3.68]) in adulthood. Post hoc analyses showed that the association with comorbidity was stronger than with either disease alone, and the associ
Published: 2023

24. Sociodemographic, lifestyle and clinical characteristics of energy-related depression symptoms:A pooled analysis of 13,965 depressed cases in 8 Dutch cohorts

Author: Vreijling, Sarah R., van Haeringen, Marije, Milaneschi, Yuri, Huider, Floris, Bot, Mariska, Amin, Najaf, Beulens, Joline W., Bremmer, Marijke A., Elders, Petra J., Galesloot, Tessel E., Kiemeney, Lambertus A., van Loo, Hanna M., Picavet, H. Susan J., Rutters, Femke, van der Spek, Ashley, van de Wiel, Anne M., van Duijn, Cornelia, Feskens, Edith J.M., Hartman, Catharina A., Oldehinkel, Albertine J., Smit, Jan H., Verschuren, W. M.Monique, Willemsen, Gonneke, de Geus, Eco J.C., Boomsma, Dorret I., Penninx, Brenda W.J.H., Lamers, Femke, Jansen, Rick, Vreijling, Sarah R., van Haeringen, Marije, Milaneschi, Yuri, Huider, Floris, Bot, Mariska, Amin, Najaf, Beulens, Joline W., Bremmer, Marijke A., Elders, Petra J., Galesloot, Tessel E., Kiemeney, Lambertus A., van Loo, Hanna M., Picavet, H. Susan J., Rutters, Femke, van der Spek, Ashley, van de Wiel, Anne M., van Duijn, Cornelia, Feskens, Edith J.M., Hartman, Catharina A., Oldehinkel, Albertine J., Smit, Jan H., Verschuren, W. M.Monique, Willemsen, Gonneke, de Geus, Eco J.C., Boomsma, Dorret I., Penninx, Brenda W.J.H., Lamers, Femke, and Jansen, Rick
Abstract: Background: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.g. increased BMI and inflammatory markers). This clustering is proposed to reflect a more homogeneous depression pathology. This study examines to what extent energy-related symptoms are associated and share sociodemographic, lifestyle and clinical characteristics. Methods: Data were available from 13,965 participants from eight Dutch cohorts with DSM-5 lifetime major depression assessed by the Lifetime Depression Assessment Self-report (LIDAS) questionnaire. Information on four energy-related depression symptoms were extracted: energy loss, increased appetite, increased weight, and hypersomnia. Tetrachoric correlations between these symptoms, and associations of these symptoms with sociodemographic (sex, age, education), lifestyle (physical activity, BMI, smoking) and clinical characteristics (age of onset, episode duration, history, treatment and recency, and self-reported comorbidity) were computed. Results: Correlations between energy-related symptoms were overall higher than those with other depression symptoms and varied from 0.90 (increased appetite vs increased weight) to 0.11 (increased appetite vs energy loss). All energy-related symptoms were strongly associated with higher BMI and a more severe clinical profile. Patients with increased appetite were more often smokers, and only patients with increased appetite or weight more often had a self-reported diagnosis of PTSD (OR = 1.17, p = 2.91E-08) and eating disorder (OR = 1.40, p = 4.08E-17). Conclusions: The symptom-specific associations may have consequences for a profile integrating these symptoms, which can be used to reflect immuno-metabolic depression. They indicate the need to study immuno-metabolic depression at individual symptom resolution as a starting point.
Published: 2023

25. Sociodemographic, lifestyle and clinical characteristics of energy-related depression symptoms : A pooled analysis of 13,965 depressed cases in 8 Dutch cohorts

Author: Vreijling, Sarah R., van Haeringen, Marije, Milaneschi, Yuri, Huider, Floris, Bot, Mariska, Amin, Najaf, Beulens, Joline W., Bremmer, Marijke A., Elders, Petra J., Galesloot, Tessel E., Kiemeney, Lambertus A., van Loo, Hanna M., Picavet, H.S.J., Rutters, Femke, van der Spek, Ashley, van de Wiel, Anne M., van Duijn, Cornelia, Feskens, Edith J.M., Hartman, Catharina A., Oldehinkel, Albertine J., Smit, Jan H., Verschuren, W.M.M., Willemsen, Gonneke, de Geus, Eco J.C., Boomsma, Dorret I., Penninx, Brenda W.J.H., Lamers, Femke, Jansen, Rick, Vreijling, Sarah R., van Haeringen, Marije, Milaneschi, Yuri, Huider, Floris, Bot, Mariska, Amin, Najaf, Beulens, Joline W., Bremmer, Marijke A., Elders, Petra J., Galesloot, Tessel E., Kiemeney, Lambertus A., van Loo, Hanna M., Picavet, H.S.J., Rutters, Femke, van der Spek, Ashley, van de Wiel, Anne M., van Duijn, Cornelia, Feskens, Edith J.M., Hartman, Catharina A., Oldehinkel, Albertine J., Smit, Jan H., Verschuren, W.M.M., Willemsen, Gonneke, de Geus, Eco J.C., Boomsma, Dorret I., Penninx, Brenda W.J.H., Lamers, Femke, and Jansen, Rick
Abstract: Background: In a substantial subgroup of depressed patients, atypical, energy-related depression symptoms (e.g. increased appetite/weight, hypersomnia, loss of energy) tend to cluster with immuno-metabolic dysregulations (e.g. increased BMI and inflammatory markers). This clustering is proposed to reflect a more homogeneous depression pathology. This study examines to what extent energy-related symptoms are associated and share sociodemographic, lifestyle and clinical characteristics. Methods: Data were available from 13,965 participants from eight Dutch cohorts with DSM-5 lifetime major depression assessed by the Lifetime Depression Assessment Self-report (LIDAS) questionnaire. Information on four energy-related depression symptoms were extracted: energy loss, increased appetite, increased weight, and hypersomnia. Tetrachoric correlations between these symptoms, and associations of these symptoms with sociodemographic (sex, age, education), lifestyle (physical activity, BMI, smoking) and clinical characteristics (age of onset, episode duration, history, treatment and recency, and self-reported comorbidity) were computed. Results: Correlations between energy-related symptoms were overall higher than those with other depression symptoms and varied from 0.90 (increased appetite vs increased weight) to 0.11 (increased appetite vs energy loss). All energy-related symptoms were strongly associated with higher BMI and a more severe clinical profile. Patients with increased appetite were more often smokers, and only patients with increased appetite or weight more often had a self-reported diagnosis of PTSD (OR = 1.17, p = 2.91E-08) and eating disorder (OR = 1.40, p = 4.08E-17). Conclusions: The symptom-specific associations may have consequences for a profile integrating these symptoms, which can be used to reflect immuno-metabolic depression. They indicate the need to study immuno-metabolic depression at individual symptom resolution as a starting point.
Published: 2023

26. Sociodemographic, lifestyle and clinical characteristics of energy-related depression symptoms: A pooled analysis of 13,965 depressed cases in 8 Dutch cohorts

Author: Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiometabolic Health, Vreijling, Sarah R., van Haeringen, Marije, Milaneschi, Yuri, Huider, Floris, Bot, Mariska, Amin, Najaf, Bremmer, Marijke A., Elders, Petra J., Galesloot, Tessel E., Kiemeney, Lambertus A., van Loo, Hanna M., Picavet, H. Susan J., Rutters, Femke, van der Spek, Ashley, van de Wiel, Anne M., van Duijn, Cornelia, Feskens, Edith J.M., Hartman, Catharina A., Oldehinkel, Albertine J., Smit, Jan H., Verschuren, W. M.Monique, Willemsen, Gonneke, de Geus, Eco J.C., Boomsma, Dorret I., Penninx, Brenda W.J.H., Lamers, Femke, Jansen, Rick, Circulatory Health, JC onderzoeksprogramma Cardiovasculaire Epidemiologie, Cardiometabolic Health, Vreijling, Sarah R., van Haeringen, Marije, Milaneschi, Yuri, Huider, Floris, Bot, Mariska, Amin, Najaf, Bremmer, Marijke A., Elders, Petra J., Galesloot, Tessel E., Kiemeney, Lambertus A., van Loo, Hanna M., Picavet, H. Susan J., Rutters, Femke, van der Spek, Ashley, van de Wiel, Anne M., van Duijn, Cornelia, Feskens, Edith J.M., Hartman, Catharina A., Oldehinkel, Albertine J., Smit, Jan H., Verschuren, W. M.Monique, Willemsen, Gonneke, de Geus, Eco J.C., Boomsma, Dorret I., Penninx, Brenda W.J.H., Lamers, Femke, and Jansen, Rick
Published: 2023

27. GWAS Meta-Analysis of Suicide Attempt:Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Author: Docherty, Anna R., Mullins, Niamh, Ashley-Koch, Allison E., Qin, Xuejun, Coleman, Jonathan R.I., Shabalin, Andrey, Kang, Joo Eun, Murnyak, Balasz, Wendt, Frank, Adams, Mark, Campos, Adrian I., DiBlasi, Emily, Fullerton, Janice M., Kranzler, Henry R., Bakian, Amanda V., Monson, Eric T., Rentería, Miguel E., Walss-Bass, Consuelo, Andreassen, Ole A., Behera, Chittaranjan, Bulik, Cynthia M., Edenberg, Howard J., Kessler, Ronald C., John Mann, J., Nurnberger, John I., Pistis, Giorgio, Streit, Fabian, Ursano, Robert J., Polimanti, Renato, Dennis, Michelle, Garrett, Melanie, Hair, Lauren, Harvey, Philip, Hauser, Elizabeth R., Hauser, Michael A., Huffman, Jennifer, Jacobson, Daniel, Madduri, Ravi, McMahon, Benjamin, Oslin, David W., Trafton, Jodie, Awasthi, Swapnil, Berrettini, Wade H., Bohus, Martin, Chang, Xiao, Chen, Hsi Chung, Chen, Wei J., Christensen, Erik D.M.D., Crow, Scott, Duriez, Philibert, Edwards, Alexis C., Fernández-Aranda, Fernando, Galfalvy, Hanga, Gandal, Michael, Gorwood, Philip, Guo, Yiran, Hafferty, Jonathan D., Hakonarson, Hakon, Halmi, Katherine A., Hishimoto, Akitoyo, Jain, Sonia, Jamain, Stéphane, Jiménez-Murcia, Susana, Johnson, Craig, Kaplan, Allan S., Kaye, Walter H., Keel, Pamela K., Kennedy, James L., Kim, Minsoo, Klump, Kelly L., Levey, Daniel F., Li, Dong, Liao, Shih Cheng, Lieb, Klaus, Lilenfeld, Lisa, Marshall, Christian R., Mitchell, James E., Okazaki, Satoshi, Otsuka, Ikuo, Pinto, Dalila, Powers, Abigail, Ramoz, Nicolas, Ripke, Stephan, Roepke, Stefan, Rozanov, Vsevolod, Scherer, Stephen W., Schmahl, Christian, Sokolowski, Marcus, Starnawska, Anna, Strober, Michael, Su, Mei Hsin, Thornton, Laura M., Treasure, Janet, Ware, Erin B., Watson, Hunna J., Witt, Stephanie H., Blake Woodside, D., Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Appadurai, Vivek, Artigas, María Soler, Van Der Auwera, Sandra, Helena Azevedo, M., Bass, Nicholas, Bau, Claiton H.D., Baune, Bernhard T., Bellivier, Frank, Berger, Klaus, Biernacka, Joanna M., Bigdeli, Tim B., Binder, Elisabeth B., Boehnke, Michael, Boks, Marco P., Braff, David L., Bryant, Richard, Budde, Monika, Byrne, Enda M., Cahn, Wiepke, Castelao, Enrique, Cervilla, Jorge A., Chaumette, Boris, Corvin, Aiden, Craddock, Nicholas, Djurovic, Srdjan, Foo, Jerome C., Forstner, Andreas J., Frye, Mark, Gatt, Justine M., Giegling, Ina, Grabe, Hans J., Green, Melissa J., Grevet, Eugenio H., Grigoroiu-Serbanescu, Maria, Gutierrez, Blanca, Guzman-Parra, Jose, Hamshere, Marian L., Hartmann, Annette M., Hauser, Joanna, Heilmann-Heimbach, Stefanie, Hoffmann, Per, Ising, Marcus, Jones, Ian, Jones, Lisa A., Jonsson, Lina, Kahn, René S., Kelsoe, John R., Kendler, Kenneth S., Kloiber, Stefan, Koenen, Karestan C., Kogevinas, Manolis, Krebs, Marie Odile, Landén, Mikael, Leboyer, Marion, Lee, Phil H., Levinson, Douglas F., Liao, Calwing, Lissowska, Jolanta, Mayoral, Fermin, McElroy, Susan L., McGrath, Patrick, McGuffin, Peter, McQuillin, Andrew, Mehta, Divya, Melle, Ingrid, Mitchell, Philip B., Molina, Esther, Morken, Gunnar, Nievergelt, Caroline, Nöthen, Markus M., O'Donovan, Michael C., Ophoff, Roel A., Owen, Michael J., Pato, Carlos, Pato, Michele T., Penninx, Brenda W.J.H., Potash, James B., Power, Robert A., Preisig, Martin, Quested, Digby, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Richarte, Vanesa, Rietschel, Marcella, Rivera, Margarita, Roberts, Andrea, Roberts, Gloria, Rouleau, Guy A., Rovaris, Diego L., Sanders, Alan R., Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Serretti, Alessandro, Shi, Jianxin, Sirignano, Lea, Sklar, Pamela, Smeland, Olav B., Smoller, Jordan W., Sonuga-Barke, Edmund J.S., Trzaskowski, MacIej, Tsuang, Ming T., Turecki, Gustavo, Vilar-Ribó, Laura, Vincent, John B., Völzke, Henry, Walters, James T.R., Weickert, Cynthia Shannon, Weickert, Thomas W., Weissman, Myrna M., Williams, Leanne M., Wray, Naomi R., Zai, Clement C., Agerbo, Esben, Børglum, Anders D., Breen, Gerome, Demontis, Ditte, Erlangsen, Annette, Gelernter, Joel, Glatt, Stephen J., Hougaard, David M., Hwu, Hai Gwo, Kuo, Po Hsiu, Lewis, Cathryn M., Li, Qingqin S., Liu, Chih Min, Martin, Nicholas G., McIntosh, Andrew M., Medland, Sarah E., Mors, Ole, Nordentoft, Merete, Olsen, Catherine M., Porteous, David, Smith, Daniel J., Stahl, Eli A., Stein, Murray B., Wasserman, Danuta, Werge, Thomas, Whiteman, David C., Willour, Virginia, Coon, Hilary, Beckham, Jean C., Kimbrel, Nathan A., Ruderfer, Douglas M., Docherty, Anna R., Mullins, Niamh, Ashley-Koch, Allison E., Qin, Xuejun, Coleman, Jonathan R.I., Shabalin, Andrey, Kang, Joo Eun, Murnyak, Balasz, Wendt, Frank, Adams, Mark, Campos, Adrian I., DiBlasi, Emily, Fullerton, Janice M., Kranzler, Henry R., Bakian, Amanda V., Monson, Eric T., Rentería, Miguel E., Walss-Bass, Consuelo, Andreassen, Ole A., Behera, Chittaranjan, Bulik, Cynthia M., Edenberg, Howard J., Kessler, Ronald C., John Mann, J., Nurnberger, John I., Pistis, Giorgio, Streit, Fabian, Ursano, Robert J., Polimanti, Renato, Dennis, Michelle, Garrett, Melanie, Hair, Lauren, Harvey, Philip, Hauser, Elizabeth R., Hauser, Michael A., Huffman, Jennifer, Jacobson, Daniel, Madduri, Ravi, McMahon, Benjamin, Oslin, David W., Trafton, Jodie, Awasthi, Swapnil, Berrettini, Wade H., Bohus, Martin, Chang, Xiao, Chen, Hsi Chung, Chen, Wei J., Christensen, Erik D.M.D., Crow, Scott, Duriez, Philibert, Edwards, Alexis C., Fernández-Aranda, Fernando, Galfalvy, Hanga, Gandal, Michael, Gorwood, Philip, Guo, Yiran, Hafferty, Jonathan D., Hakonarson, Hakon, Halmi, Katherine A., Hishimoto, Akitoyo, Jain, Sonia, Jamain, Stéphane, Jiménez-Murcia, Susana, Johnson, Craig, Kaplan, Allan S., Kaye, Walter H., Keel, Pamela K., Kennedy, James L., Kim, Minsoo, Klump, Kelly L., Levey, Daniel F., Li, Dong, Liao, Shih Cheng, Lieb, Klaus, Lilenfeld, Lisa, Marshall, Christian R., Mitchell, James E., Okazaki, Satoshi, Otsuka, Ikuo, Pinto, Dalila, Powers, Abigail, Ramoz, Nicolas, Ripke, Stephan, Roepke, Stefan, Rozanov, Vsevolod, Scherer, Stephen W., Schmahl, Christian, Sokolowski, Marcus, Starnawska, Anna, Strober, Michael, Su, Mei Hsin, Thornton, Laura M., Treasure, Janet, Ware, Erin B., Watson, Hunna J., Witt, Stephanie H., Blake Woodside, D., Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Appadurai, Vivek, Artigas, María Soler, Van Der Auwera, Sandra, Helena Azevedo, M., Bass, Nicholas, Bau, Claiton H.D., Baune, Bernhard T., Bellivier, Frank, Berger, Klaus, Biernacka, Joanna M., Bigdeli, Tim B., Binder, Elisabeth B., Boehnke, Michael, Boks, Marco P., Braff, David L., Bryant, Richard, Budde, Monika, Byrne, Enda M., Cahn, Wiepke, Castelao, Enrique, Cervilla, Jorge A., Chaumette, Boris, Corvin, Aiden, Craddock, Nicholas, Djurovic, Srdjan, Foo, Jerome C., Forstner, Andreas J., Frye, Mark, Gatt, Justine M., Giegling, Ina, Grabe, Hans J., Green, Melissa J., Grevet, Eugenio H., Grigoroiu-Serbanescu, Maria, Gutierrez, Blanca, Guzman-Parra, Jose, Hamshere, Marian L., Hartmann, Annette M., Hauser, Joanna, Heilmann-Heimbach, Stefanie, Hoffmann, Per, Ising, Marcus, Jones, Ian, Jones, Lisa A., Jonsson, Lina, Kahn, René S., Kelsoe, John R., Kendler, Kenneth S., Kloiber, Stefan, Koenen, Karestan C., Kogevinas, Manolis, Krebs, Marie Odile, Landén, Mikael, Leboyer, Marion, Lee, Phil H., Levinson, Douglas F., Liao, Calwing, Lissowska, Jolanta, Mayoral, Fermin, McElroy, Susan L., McGrath, Patrick, McGuffin, Peter, McQuillin, Andrew, Mehta, Divya, Melle, Ingrid, Mitchell, Philip B., Molina, Esther, Morken, Gunnar, Nievergelt, Caroline, Nöthen, Markus M., O'Donovan, Michael C., Ophoff, Roel A., Owen, Michael J., Pato, Carlos, Pato, Michele T., Penninx, Brenda W.J.H., Potash, James B., Power, Robert A., Preisig, Martin, Quested, Digby, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Richarte, Vanesa, Rietschel, Marcella, Rivera, Margarita, Roberts, Andrea, Roberts, Gloria, Rouleau, Guy A., Rovaris, Diego L., Sanders, Alan R., Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Serretti, Alessandro, Shi, Jianxin, Sirignano, Lea, Sklar, Pamela, Smeland, Olav B., Smoller, Jordan W., Sonuga-Barke, Edmund J.S., Trzaskowski, MacIej, Tsuang, Ming T., Turecki, Gustavo, Vilar-Ribó, Laura, Vincent, John B., Völzke, Henry, Walters, James T.R., Weickert, Cynthia Shannon, Weickert, Thomas W., Weissman, Myrna M., Williams, Leanne M., Wray, Naomi R., Zai, Clement C., Agerbo, Esben, Børglum, Anders D., Breen, Gerome, Demontis, Ditte, Erlangsen, Annette, Gelernter, Joel, Glatt, Stephen J., Hougaard, David M., Hwu, Hai Gwo, Kuo, Po Hsiu, Lewis, Cathryn M., Li, Qingqin S., Liu, Chih Min, Martin, Nicholas G., McIntosh, Andrew M., Medland, Sarah E., Mors, Ole, Nordentoft, Merete, Olsen, Catherine M., Porteous, David, Smith, Daniel J., Stahl, Eli A., Stein, Murray B., Wasserman, Danuta, Werge, Thomas, Whiteman, David C., Willour, Virginia, Coon, Hilary, Beckham, Jean C., Kimbrel, Nathan A., and Ruderfer, Douglas M.
Abstract: Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide asso-ciation studies (GWASs) recently discovered and cross- validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic co-horts from both studies to conduct the largest GWAS meta- analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry ad-mixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and ge-netic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10–8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10–80). Significant brain tissue gene expression and drug set en-richment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major de-pressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical pheno-types. These findings provide insight into genetic fa, Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attemp
Published: 2023

28. GWAS Meta-Analysis of Suicide Attempt:Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors

Author: Docherty, Anna R., Mullins, Niamh, Ashley-Koch, Allison E., Qin, Xuejun, Coleman, Jonathan R.I., Shabalin, Andrey, Kang, Joo Eun, Murnyak, Balasz, Wendt, Frank, Adams, Mark, Campos, Adrian I., DiBlasi, Emily, Fullerton, Janice M., Kranzler, Henry R., Bakian, Amanda V., Monson, Eric T., Rentería, Miguel E., Walss-Bass, Consuelo, Andreassen, Ole A., Behera, Chittaranjan, Bulik, Cynthia M., Edenberg, Howard J., Kessler, Ronald C., John Mann, J., Nurnberger, John I., Pistis, Giorgio, Streit, Fabian, Ursano, Robert J., Polimanti, Renato, Dennis, Michelle, Garrett, Melanie, Hair, Lauren, Harvey, Philip, Hauser, Elizabeth R., Hauser, Michael A., Huffman, Jennifer, Jacobson, Daniel, Madduri, Ravi, McMahon, Benjamin, Oslin, David W., Trafton, Jodie, Awasthi, Swapnil, Berrettini, Wade H., Bohus, Martin, Chang, Xiao, Chen, Hsi Chung, Chen, Wei J., Christensen, Erik D.M.D., Crow, Scott, Duriez, Philibert, Edwards, Alexis C., Fernández-Aranda, Fernando, Galfalvy, Hanga, Gandal, Michael, Gorwood, Philip, Guo, Yiran, Hafferty, Jonathan D., Hakonarson, Hakon, Halmi, Katherine A., Hishimoto, Akitoyo, Jain, Sonia, Jamain, Stéphane, Jiménez-Murcia, Susana, Johnson, Craig, Kaplan, Allan S., Kaye, Walter H., Keel, Pamela K., Kennedy, James L., Kim, Minsoo, Klump, Kelly L., Levey, Daniel F., Li, Dong, Liao, Shih Cheng, Lieb, Klaus, Lilenfeld, Lisa, Marshall, Christian R., Mitchell, James E., Okazaki, Satoshi, Otsuka, Ikuo, Pinto, Dalila, Powers, Abigail, Ramoz, Nicolas, Ripke, Stephan, Roepke, Stefan, Rozanov, Vsevolod, Scherer, Stephen W., Schmahl, Christian, Sokolowski, Marcus, Starnawska, Anna, Strober, Michael, Su, Mei Hsin, Thornton, Laura M., Treasure, Janet, Ware, Erin B., Watson, Hunna J., Witt, Stephanie H., Blake Woodside, D., Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Appadurai, Vivek, Artigas, María Soler, Van Der Auwera, Sandra, Helena Azevedo, M., Bass, Nicholas, Bau, Claiton H.D., Baune, Bernhard T., Bellivier, Frank, Berger, Klaus, Biernacka, Joanna M., Bigdeli, Tim B., Binder, Elisabeth B., Boehnke, Michael, Boks, Marco P., Braff, David L., Bryant, Richard, Budde, Monika, Byrne, Enda M., Cahn, Wiepke, Castelao, Enrique, Cervilla, Jorge A., Chaumette, Boris, Corvin, Aiden, Craddock, Nicholas, Djurovic, Srdjan, Foo, Jerome C., Forstner, Andreas J., Frye, Mark, Gatt, Justine M., Giegling, Ina, Grabe, Hans J., Green, Melissa J., Grevet, Eugenio H., Grigoroiu-Serbanescu, Maria, Gutierrez, Blanca, Guzman-Parra, Jose, Hamshere, Marian L., Hartmann, Annette M., Hauser, Joanna, Heilmann-Heimbach, Stefanie, Hoffmann, Per, Ising, Marcus, Jones, Ian, Jones, Lisa A., Jonsson, Lina, Kahn, René S., Kelsoe, John R., Kendler, Kenneth S., Kloiber, Stefan, Koenen, Karestan C., Kogevinas, Manolis, Krebs, Marie Odile, Landén, Mikael, Leboyer, Marion, Lee, Phil H., Levinson, Douglas F., Liao, Calwing, Lissowska, Jolanta, Mayoral, Fermin, McElroy, Susan L., McGrath, Patrick, McGuffin, Peter, McQuillin, Andrew, Mehta, Divya, Melle, Ingrid, Mitchell, Philip B., Molina, Esther, Morken, Gunnar, Nievergelt, Caroline, Nöthen, Markus M., O'Donovan, Michael C., Ophoff, Roel A., Owen, Michael J., Pato, Carlos, Pato, Michele T., Penninx, Brenda W.J.H., Potash, James B., Power, Robert A., Preisig, Martin, Quested, Digby, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Richarte, Vanesa, Rietschel, Marcella, Rivera, Margarita, Roberts, Andrea, Roberts, Gloria, Rouleau, Guy A., Rovaris, Diego L., Sanders, Alan R., Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Serretti, Alessandro, Shi, Jianxin, Sirignano, Lea, Sklar, Pamela, Smeland, Olav B., Smoller, Jordan W., Sonuga-Barke, Edmund J.S., Trzaskowski, MacIej, Tsuang, Ming T., Turecki, Gustavo, Vilar-Ribó, Laura, Vincent, John B., Völzke, Henry, Walters, James T.R., Weickert, Cynthia Shannon, Weickert, Thomas W., Weissman, Myrna M., Williams, Leanne M., Wray, Naomi R., Zai, Clement C., Agerbo, Esben, Børglum, Anders D., Breen, Gerome, Demontis, Ditte, Erlangsen, Annette, Gelernter, Joel, Glatt, Stephen J., Hougaard, David M., Hwu, Hai Gwo, Kuo, Po Hsiu, Lewis, Cathryn M., Li, Qingqin S., Liu, Chih Min, Martin, Nicholas G., McIntosh, Andrew M., Medland, Sarah E., Mors, Ole, Nordentoft, Merete, Olsen, Catherine M., Porteous, David, Smith, Daniel J., Stahl, Eli A., Stein, Murray B., Wasserman, Danuta, Werge, Thomas, Whiteman, David C., Willour, Virginia, Coon, Hilary, Beckham, Jean C., Kimbrel, Nathan A., Ruderfer, Douglas M., Docherty, Anna R., Mullins, Niamh, Ashley-Koch, Allison E., Qin, Xuejun, Coleman, Jonathan R.I., Shabalin, Andrey, Kang, Joo Eun, Murnyak, Balasz, Wendt, Frank, Adams, Mark, Campos, Adrian I., DiBlasi, Emily, Fullerton, Janice M., Kranzler, Henry R., Bakian, Amanda V., Monson, Eric T., Rentería, Miguel E., Walss-Bass, Consuelo, Andreassen, Ole A., Behera, Chittaranjan, Bulik, Cynthia M., Edenberg, Howard J., Kessler, Ronald C., John Mann, J., Nurnberger, John I., Pistis, Giorgio, Streit, Fabian, Ursano, Robert J., Polimanti, Renato, Dennis, Michelle, Garrett, Melanie, Hair, Lauren, Harvey, Philip, Hauser, Elizabeth R., Hauser, Michael A., Huffman, Jennifer, Jacobson, Daniel, Madduri, Ravi, McMahon, Benjamin, Oslin, David W., Trafton, Jodie, Awasthi, Swapnil, Berrettini, Wade H., Bohus, Martin, Chang, Xiao, Chen, Hsi Chung, Chen, Wei J., Christensen, Erik D.M.D., Crow, Scott, Duriez, Philibert, Edwards, Alexis C., Fernández-Aranda, Fernando, Galfalvy, Hanga, Gandal, Michael, Gorwood, Philip, Guo, Yiran, Hafferty, Jonathan D., Hakonarson, Hakon, Halmi, Katherine A., Hishimoto, Akitoyo, Jain, Sonia, Jamain, Stéphane, Jiménez-Murcia, Susana, Johnson, Craig, Kaplan, Allan S., Kaye, Walter H., Keel, Pamela K., Kennedy, James L., Kim, Minsoo, Klump, Kelly L., Levey, Daniel F., Li, Dong, Liao, Shih Cheng, Lieb, Klaus, Lilenfeld, Lisa, Marshall, Christian R., Mitchell, James E., Okazaki, Satoshi, Otsuka, Ikuo, Pinto, Dalila, Powers, Abigail, Ramoz, Nicolas, Ripke, Stephan, Roepke, Stefan, Rozanov, Vsevolod, Scherer, Stephen W., Schmahl, Christian, Sokolowski, Marcus, Starnawska, Anna, Strober, Michael, Su, Mei Hsin, Thornton, Laura M., Treasure, Janet, Ware, Erin B., Watson, Hunna J., Witt, Stephanie H., Blake Woodside, D., Yilmaz, Zeynep, Zillich, Lea, Adolfsson, Rolf, Agartz, Ingrid, Alda, Martin, Alfredsson, Lars, Appadurai, Vivek, Artigas, María Soler, Van Der Auwera, Sandra, Helena Azevedo, M., Bass, Nicholas, Bau, Claiton H.D., Baune, Bernhard T., Bellivier, Frank, Berger, Klaus, Biernacka, Joanna M., Bigdeli, Tim B., Binder, Elisabeth B., Boehnke, Michael, Boks, Marco P., Braff, David L., Bryant, Richard, Budde, Monika, Byrne, Enda M., Cahn, Wiepke, Castelao, Enrique, Cervilla, Jorge A., Chaumette, Boris, Corvin, Aiden, Craddock, Nicholas, Djurovic, Srdjan, Foo, Jerome C., Forstner, Andreas J., Frye, Mark, Gatt, Justine M., Giegling, Ina, Grabe, Hans J., Green, Melissa J., Grevet, Eugenio H., Grigoroiu-Serbanescu, Maria, Gutierrez, Blanca, Guzman-Parra, Jose, Hamshere, Marian L., Hartmann, Annette M., Hauser, Joanna, Heilmann-Heimbach, Stefanie, Hoffmann, Per, Ising, Marcus, Jones, Ian, Jones, Lisa A., Jonsson, Lina, Kahn, René S., Kelsoe, John R., Kendler, Kenneth S., Kloiber, Stefan, Koenen, Karestan C., Kogevinas, Manolis, Krebs, Marie Odile, Landén, Mikael, Leboyer, Marion, Lee, Phil H., Levinson, Douglas F., Liao, Calwing, Lissowska, Jolanta, Mayoral, Fermin, McElroy, Susan L., McGrath, Patrick, McGuffin, Peter, McQuillin, Andrew, Mehta, Divya, Melle, Ingrid, Mitchell, Philip B., Molina, Esther, Morken, Gunnar, Nievergelt, Caroline, Nöthen, Markus M., O'Donovan, Michael C., Ophoff, Roel A., Owen, Michael J., Pato, Carlos, Pato, Michele T., Penninx, Brenda W.J.H., Potash, James B., Power, Robert A., Preisig, Martin, Quested, Digby, Ramos-Quiroga, Josep Antoni, Reif, Andreas, Ribasés, Marta, Richarte, Vanesa, Rietschel, Marcella, Rivera, Margarita, Roberts, Andrea, Roberts, Gloria, Rouleau, Guy A., Rovaris, Diego L., Sanders, Alan R., Schofield, Peter R., Schulze, Thomas G., Scott, Laura J., Serretti, Alessandro, Shi, Jianxin, Sirignano, Lea, Sklar, Pamela, Smeland, Olav B., Smoller, Jordan W., Sonuga-Barke, Edmund J.S., Trzaskowski, MacIej, Tsuang, Ming T., Turecki, Gustavo, Vilar-Ribó, Laura, Vincent, John B., Völzke, Henry, Walters, James T.R., Weickert, Cynthia Shannon, Weickert, Thomas W., Weissman, Myrna M., Williams, Leanne M., Wray, Naomi R., Zai, Clement C., Agerbo, Esben, Børglum, Anders D., Breen, Gerome, Demontis, Ditte, Erlangsen, Annette, Gelernter, Joel, Glatt, Stephen J., Hougaard, David M., Hwu, Hai Gwo, Kuo, Po Hsiu, Lewis, Cathryn M., Li, Qingqin S., Liu, Chih Min, Martin, Nicholas G., McIntosh, Andrew M., Medland, Sarah E., Mors, Ole, Nordentoft, Merete, Olsen, Catherine M., Porteous, David, Smith, Daniel J., Stahl, Eli A., Stein, Murray B., Wasserman, Danuta, Werge, Thomas, Whiteman, David C., Willour, Virginia, Coon, Hilary, Beckham, Jean C., Kimbrel, Nathan A., and Ruderfer, Douglas M.
Abstract: Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide asso-ciation studies (GWASs) recently discovered and cross- validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic co-horts from both studies to conduct the largest GWAS meta- analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry ad-mixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and ge-netic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10–8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10–80). Significant brain tissue gene expression and drug set en-richment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major de-pressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical pheno-types. These findings provide insight into genetic fa, Objective: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and crossvalidated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS metaanalysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. Methods: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. Results: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. Conclusions: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attemp
Published: 2023

29. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Blokland, Gabriëlla A.M., Grove, Jakob, Chen, Chia-yen, Cotsapas, Chris, Tobet, Stuart, Sullivan, Patrick F., Boomsma, Dorret I., Penninx, Brenda W.J.H., Hottenga, Jouke-Jan, de Geus, Eco J.C., Willemsen, Gonneke, Milaneschi, Yuri, Als, Thomas D., Børglum, Anders D., Petryshen, Tracey L., Smoller, Jordan W., Goldstein, Jill M., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, iPSYCH, Blokland, Gabriëlla A.M., Grove, Jakob, Chen, Chia-yen, Cotsapas, Chris, Tobet, Stuart, Sullivan, Patrick F., Boomsma, Dorret I., Penninx, Brenda W.J.H., Hottenga, Jouke-Jan, de Geus, Eco J.C., Willemsen, Gonneke, Milaneschi, Yuri, Als, Thomas D., Børglum, Anders D., Petryshen, Tracey L., Smoller, Jordan W., Goldstein, Jill M., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, and iPSYCH
Abstract: Background Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neurona
Published: 2022
Full Text: View/download PDF

30. Associations of depression and regional brain structure across the adult lifespan : Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Objective: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. Methods: We included 3,447 participants aged 18–89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. Results: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = −0.15/ rstatus = −0.22), rACC thickness (rsymptoms = −0.20/ rstatus = −0.25), hippocampal volume (rsymptoms = −0.13/ rstatus = 0.13) and total GMV (rsymptoms = −0.21/ rstatus = −0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. Conclusions: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied
Published: 2022
Full Text: View/download PDF

31. Associations of depression and regional brain structure across the adult lifespan : Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Objective: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. Methods: We included 3,447 participants aged 18–89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. Results: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = −0.15/ rstatus = −0.22), rACC thickness (rsymptoms = −0.20/ rstatus = −0.25), hippocampal volume (rsymptoms = −0.13/ rstatus = 0.13) and total GMV (rsymptoms = −0.21/ rstatus = −0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. Conclusions: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied
Published: 2022
Full Text: View/download PDF

32. Associations of depression and regional brain structure across the adult lifespan : Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Objective: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. Methods: We included 3,447 participants aged 18–89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. Results: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = −0.15/ rstatus = −0.22), rACC thickness (rsymptoms = −0.20/ rstatus = −0.25), hippocampal volume (rsymptoms = −0.13/ rstatus = 0.13) and total GMV (rsymptoms = −0.21/ rstatus = −0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. Conclusions: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied
Published: 2022
Full Text: View/download PDF

33. Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis

Author: Siddi, Sara, Giné-Vázquez, Iago, Bailon, Raquel, Matcham, Faith, Lamers, Femke, Kontaxis, Spyridon, Laporta, Estela, Garcia, Esther, Arranz, Belen, Dalla Costa, Gloria, Guerrero, Ana Isabel, Zabalza, Ana, Buron, Mathias Due, Comi, Giancarlo, Leocani, Letizia, Annas, Peter, Hotopf, Matthew, Penninx, Brenda W.J.H., Magyari, Melinda, Sørensen, Per S., Montalban, Xavier, Lavelle, Grace, Ivan, Alina, Oetzmann, Carolin, White, Katie M., Difrancesco, Sonia, Locatelli, Patrick, Mohr, David C., Aguiló, Jordi, Narayan, Vaibhav, Folarin, Amos, Dobson, Richard J.B., Dineley, Judith, Leightley, Daniel, Cummins, Nicholas, Vairavan, Srinivasan, Ranjan, Yathart, Rashid, Zulqarnain, Rintala, Aki, Girolamo, Giovanni De, Preti, Antonio, Simblett, Sara, Wykes, Til, Myin-Germeys, Inez, Haro, Josep Maria, Siddi, Sara, Giné-Vázquez, Iago, Bailon, Raquel, Matcham, Faith, Lamers, Femke, Kontaxis, Spyridon, Laporta, Estela, Garcia, Esther, Arranz, Belen, Dalla Costa, Gloria, Guerrero, Ana Isabel, Zabalza, Ana, Buron, Mathias Due, Comi, Giancarlo, Leocani, Letizia, Annas, Peter, Hotopf, Matthew, Penninx, Brenda W.J.H., Magyari, Melinda, Sørensen, Per S., Montalban, Xavier, Lavelle, Grace, Ivan, Alina, Oetzmann, Carolin, White, Katie M., Difrancesco, Sonia, Locatelli, Patrick, Mohr, David C., Aguiló, Jordi, Narayan, Vaibhav, Folarin, Amos, Dobson, Richard J.B., Dineley, Judith, Leightley, Daniel, Cummins, Nicholas, Vairavan, Srinivasan, Ranjan, Yathart, Rashid, Zulqarnain, Rintala, Aki, Girolamo, Giovanni De, Preti, Antonio, Simblett, Sara, Wykes, Til, Myin-Germeys, Inez, and Haro, Josep Maria
Abstract: Background: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDDs) and Multiple Sclerosis (MS). Methods: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse—Central Nervous System) program. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. Results: Participants with MDDs (N = 255) and MS (N = 214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. A lower mean HR and HR variation were observed between pre and during lockdown during the day for MDDs and during the night for MS. HR variation during rest periods also decreased between pre- and post-lockdown in both clinical conditions. We observed a reduction in physical activity for MDDs and MS upon the introduction of lockdowns. The group with MDDs exhibited a net increase in social interaction via social network apps over the three periods. Conclusions: Behavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.
Published: 2022

34. Biopsychosocial Response to the COVID-19 Lockdown in People with Major Depressive Disorder and Multiple Sclerosis

Author: Siddi, Sara, Giné-Vázquez, Iago, Bailon, Raquel, Matcham, Faith, Lamers, Femke, Kontaxis, Spyridon, Laporta, Estela, Garcia, Esther, Arranz, Belen, Dalla Costa, Gloria, Guerrero, Ana Isabel, Zabalza, Ana, Buron, Mathias Due, Comi, Giancarlo, Leocani, Letizia, Annas, Peter, Hotopf, Matthew, Penninx, Brenda W.J.H., Magyari, Melinda, Sørensen, Per S., Montalban, Xavier, Lavelle, Grace, Ivan, Alina, Oetzmann, Carolin, White, Katie M., Difrancesco, Sonia, Locatelli, Patrick, Mohr, David C., Aguiló, Jordi, Narayan, Vaibhav, Folarin, Amos, Dobson, Richard J.B., Dineley, Judith, Leightley, Daniel, Cummins, Nicholas, Vairavan, Srinivasan, Ranjan, Yathart, Rashid, Zulqarnain, Rintala, Aki, Girolamo, Giovanni De, Preti, Antonio, Simblett, Sara, Wykes, Til, Myin-Germeys, Inez, Haro, Josep Maria, Siddi, Sara, Giné-Vázquez, Iago, Bailon, Raquel, Matcham, Faith, Lamers, Femke, Kontaxis, Spyridon, Laporta, Estela, Garcia, Esther, Arranz, Belen, Dalla Costa, Gloria, Guerrero, Ana Isabel, Zabalza, Ana, Buron, Mathias Due, Comi, Giancarlo, Leocani, Letizia, Annas, Peter, Hotopf, Matthew, Penninx, Brenda W.J.H., Magyari, Melinda, Sørensen, Per S., Montalban, Xavier, Lavelle, Grace, Ivan, Alina, Oetzmann, Carolin, White, Katie M., Difrancesco, Sonia, Locatelli, Patrick, Mohr, David C., Aguiló, Jordi, Narayan, Vaibhav, Folarin, Amos, Dobson, Richard J.B., Dineley, Judith, Leightley, Daniel, Cummins, Nicholas, Vairavan, Srinivasan, Ranjan, Yathart, Rashid, Zulqarnain, Rintala, Aki, Girolamo, Giovanni De, Preti, Antonio, Simblett, Sara, Wykes, Til, Myin-Germeys, Inez, and Haro, Josep Maria
Abstract: Background: Changes in lifestyle, finances and work status during COVID-19 lockdowns may have led to biopsychosocial changes in people with pre-existing vulnerabilities such as Major Depressive Disorders (MDDs) and Multiple Sclerosis (MS). Methods: Data were collected as a part of the RADAR-CNS (Remote Assessment of Disease and Relapse—Central Nervous System) program. We analyzed the following data from long-term participants in a decentralized multinational study: symptoms of depression, heart rate (HR) during the day and night; social activity; sedentary state, steps and physical activity of varying intensity. Linear mixed-effects regression analyses with repeated measures were fitted to assess the changes among three time periods (pre, during and post-lockdown) across the groups, adjusting for depression severity before the pandemic and gender. Results: Participants with MDDs (N = 255) and MS (N = 214) were included in the analyses. Overall, depressive symptoms remained stable across the three periods in both groups. A lower mean HR and HR variation were observed between pre and during lockdown during the day for MDDs and during the night for MS. HR variation during rest periods also decreased between pre- and post-lockdown in both clinical conditions. We observed a reduction in physical activity for MDDs and MS upon the introduction of lockdowns. The group with MDDs exhibited a net increase in social interaction via social network apps over the three periods. Conclusions: Behavioral responses to the lockdown measured by social activity, physical activity and HR may reflect changes in stress in people with MDDs and MS. Remote technology monitoring might promptly activate an early warning of physical and social alterations in these stressful situations. Future studies must explore how stress does or does not impact depression severity.
Published: 2022

35. Associations of depression and regional brain structure across the adult lifespan : Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Objective: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. Methods: We included 3,447 participants aged 18–89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. Results: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = −0.15/ rstatus = −0.22), rACC thickness (rsymptoms = −0.20/ rstatus = −0.25), hippocampal volume (rsymptoms = −0.13/ rstatus = 0.13) and total GMV (rsymptoms = −0.21/ rstatus = −0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. Conclusions: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied
Published: 2022
Full Text: View/download PDF

36. A Delphi-method-based consensus guideline for definition of treatment-resistant depression for clinical trials

Author: Sforzini, Luca, Worrell, Courtney, Kose, Melisa, Anderson, Ian M., Aouizerate, Bruno, Arolt, Volker, Bauer, Michael, Baune, Bernhard T., Blier, Pierre, Cleare, Anthony J., Cowen, Philip J., Dinan, Timothy G., Fagiolini, Andrea, Ferrier, I. Nicol, Hegerl, Ulrich, Krystal, Andrew D., Leboyer, Marion, McAllister-Williams, R. Hamish, McIntyre, Roger S., Meyer-Lindenberg, Andreas, Miller, Andrew H., Nemeroff, Charles B., Normann, Claus, Nutt, David, Pallanti, Stefano, Pani, Luca, Penninx, Brenda W.J.H., Schatzberg, Alan F., Shelton, Richard C., Yatham, Lakshmi N., Young, Allan H., Zahn, Roland, Aislaitner, Georgios, Butlen-Ducuing, Florence, Fletcher, Christine, Haberkamp, Marion, Laughren, Thomas, Mäntylä, Fanni Laura, Schruers, Koen, Thomson, Andrew, Arteaga-Henríquez, Gara, Benedetti, Francesco, Cash-Gibson, Lucinda, Chae, Woo Ri, De Smedt, Heidi, Gold, Stefan M., Hoogendijk, Witte J.G., Mondragón, Valeria Jordán, Maron, Eduard, Martynowicz, Jadwiga, Melloni, Elisa, Otte, Christian, Perez-Fuentes, Gabriela, Poletti, Sara, Schmidt, Mark E., van de Ketterij, Edwin, Woo, Katherine, Flossbach, Yanina, Ramos-Quiroga, J. Antoni, Savitz, Adam J., Pariante, Carmine M., Sforzini, Luca, Worrell, Courtney, Kose, Melisa, Anderson, Ian M., Aouizerate, Bruno, Arolt, Volker, Bauer, Michael, Baune, Bernhard T., Blier, Pierre, Cleare, Anthony J., Cowen, Philip J., Dinan, Timothy G., Fagiolini, Andrea, Ferrier, I. Nicol, Hegerl, Ulrich, Krystal, Andrew D., Leboyer, Marion, McAllister-Williams, R. Hamish, McIntyre, Roger S., Meyer-Lindenberg, Andreas, Miller, Andrew H., Nemeroff, Charles B., Normann, Claus, Nutt, David, Pallanti, Stefano, Pani, Luca, Penninx, Brenda W.J.H., Schatzberg, Alan F., Shelton, Richard C., Yatham, Lakshmi N., Young, Allan H., Zahn, Roland, Aislaitner, Georgios, Butlen-Ducuing, Florence, Fletcher, Christine, Haberkamp, Marion, Laughren, Thomas, Mäntylä, Fanni Laura, Schruers, Koen, Thomson, Andrew, Arteaga-Henríquez, Gara, Benedetti, Francesco, Cash-Gibson, Lucinda, Chae, Woo Ri, De Smedt, Heidi, Gold, Stefan M., Hoogendijk, Witte J.G., Mondragón, Valeria Jordán, Maron, Eduard, Martynowicz, Jadwiga, Melloni, Elisa, Otte, Christian, Perez-Fuentes, Gabriela, Poletti, Sara, Schmidt, Mark E., van de Ketterij, Edwin, Woo, Katherine, Flossbach, Yanina, Ramos-Quiroga, J. Antoni, Savitz, Adam J., and Pariante, Carmine M.
Abstract: Criteria for treatment-resistant depression (TRD) and partially responsive depression (PRD) as subtypes of major depressive disorder (MDD) are not unequivocally defined. In the present document we used a Delphi-method-based consensus approach to define TRD and PRD and to serve as operational criteria for future clinical studies, especially if conducted for regulatory purposes. We reviewed the literature and brought together a group of international experts (including clinicians, academics, researchers, employees of pharmaceutical companies, regulatory bodies representatives, and one person with lived experience) to evaluate the state-of-the-art and main controversies regarding the current classification. We then provided recommendations on how to design clinical trials, and on how to guide research in unmet needs and knowledge gaps. This report will feed into one of the main objectives of the EUropean Patient-cEntric clinicAl tRial pLatforms, Innovative Medicines Initiative (EU-PEARL, IMI) MDD project, to design a protocol for platform trials of new medications for TRD/PRD.
Published: 2022

37. Sex-Dependent Shared and Nonshared Genetic Architecture Across Mood and Psychotic Disorders

Author: Blokland, Gabriëlla A.M., Grove, Jakob, Chen, Chia-yen, Cotsapas, Chris, Tobet, Stuart, Sullivan, Patrick F., Boomsma, Dorret I., Penninx, Brenda W.J.H., Hottenga, Jouke-Jan, de Geus, Eco J.C., Willemsen, Gonneke, Milaneschi, Yuri, Als, Thomas D., Børglum, Anders D., Petryshen, Tracey L., Smoller, Jordan W., Goldstein, Jill M., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, iPSYCH, Blokland, Gabriëlla A.M., Grove, Jakob, Chen, Chia-yen, Cotsapas, Chris, Tobet, Stuart, Sullivan, Patrick F., Boomsma, Dorret I., Penninx, Brenda W.J.H., Hottenga, Jouke-Jan, de Geus, Eco J.C., Willemsen, Gonneke, Milaneschi, Yuri, Als, Thomas D., Børglum, Anders D., Petryshen, Tracey L., Smoller, Jordan W., Goldstein, Jill M., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bipolar Disorder Working Group of the Psychiatric Genomics Consortium, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Sex Differences Cross-Disorder Analysis Group of the Psychiatric Genomics Consortium, and iPSYCH
Abstract: Background Sex differences in incidence and/or presentation of schizophrenia (SCZ), major depressive disorder (MDD), and bipolar disorder (BIP) are pervasive. Previous evidence for shared genetic risk and sex differences in brain abnormalities across disorders suggest possible shared sex-dependent genetic risk. Methods We conducted the largest to date genome-wide genotype-by-sex (G×S) interaction of risk for these disorders using 85,735 cases (33,403 SCZ, 19,924 BIP, and 32,408 MDD) and 109,946 controls from the PGC (Psychiatric Genomics Consortium) and iPSYCH. Results Across disorders, genome-wide significant single nucleotide polymorphism–by-sex interaction was detected for a locus encompassing NKAIN2 (rs117780815, p = 3.2 × 10−8), which interacts with sodium/potassium-transporting ATPase (adenosine triphosphatase) enzymes, implicating neuronal excitability. Three additional loci showed evidence (p < 1 × 10−6) for cross-disorder G×S interaction (rs7302529, p = 1.6 × 10−7; rs73033497, p = 8.8 × 10−7; rs7914279, p = 6.4 × 10−7), implicating various functions. Gene-based analyses identified G×S interaction across disorders (p = 8.97 × 10−7) with transcriptional inhibitor SLTM. Most significant in SCZ was a MOCOS gene locus (rs11665282, p = 1.5 × 10−7), implicating vascular endothelial cells. Secondary analysis of the PGC-SCZ dataset detected an interaction (rs13265509, p = 1.1 × 10−7) in a locus containing IDO2, a kynurenine pathway enzyme with immunoregulatory functions implicated in SCZ, BIP, and MDD. Pathway enrichment analysis detected significant G×S interaction of genes regulating vascular endothelial growth factor receptor signaling in MDD (false discovery rate-corrected p < .05). Conclusions In the largest genome-wide G×S analysis of mood and psychotic disorders to date, there was substantial genetic overlap between the sexes. However, significant sex-dependent effects were enriched for genes related to neurona
Published: 2022
Full Text: View/download PDF

38. Associations of depression and regional brain structure across the adult lifespan : Pooled analyses of six population-based and two clinical cohort studies in the European Lifebrain consortium

Author: Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., Penninx, Brenda W.J.H., Binnewies, Julia, Nawijn, Laura, Brandmaier, Andreas M., Baaré, William F.C., Bartrés-Faz, David, Drevon, Christian A., Düzel, Sandra, Fjell, Anders M., Han, Laura K.M., Knights, Ethan, Lindenberger, Ulman, Milaneschi, Yuri, Mowinckel, Athanasia M., Nyberg, Lars, Plachti, Anna, Madsen, Kathrine Skak, Solé-Padullés, Cristina, Suri, Sana, Walhovd, Kristine B., Zsoldos, Enikő, Ebmeier, Klaus P., and Penninx, Brenda W.J.H.
Abstract: Objective: Major depressive disorder has been associated with lower prefrontal thickness and hippocampal volume, but it is unknown whether this association also holds for depressive symptoms in the general population. We investigated associations of depressive symptoms and depression status with brain structures across population-based and patient-control cohorts, and explored whether these associations are similar over the lifespan and across sexes. Methods: We included 3,447 participants aged 18–89 years from six population-based and two clinical patient-control cohorts of the European Lifebrain consortium. Cross-sectional meta-analyses using individual person data were performed for associations of depressive symptoms and depression status with FreeSurfer-derived thickness of bilateral rostral anterior cingulate cortex (rACC) and medial orbitofrontal cortex (mOFC), and hippocampal and total grey matter volume (GMV), separately for population-based and clinical cohorts. Results: Across patient-control cohorts, depressive symptoms and presence of mild-to-severe depression were associated with lower mOFC thickness (rsymptoms = −0.15/ rstatus = −0.22), rACC thickness (rsymptoms = −0.20/ rstatus = −0.25), hippocampal volume (rsymptoms = −0.13/ rstatus = 0.13) and total GMV (rsymptoms = −0.21/ rstatus = −0.25). Effect sizes were slightly larger for presence of moderate-to-severe depression. Associations were similar across age groups and sex. Across population-based cohorts, no associations between depression and brain structures were observed. Conclusions: Fitting with previous meta-analyses, depressive symptoms and depression status were associated with lower mOFC, rACC thickness, and hippocampal and total grey matter volume in clinical patient-control cohorts, although effect sizes were small. The absence of consistent associations in population-based cohorts with mostly mild depressive symptoms, suggests that significantly lower thickness and volume of the studied
Published: 2022
Full Text: View/download PDF

39. Genome-wide analysis of 102,084 migraine cases identifies 123 risk loci and subtype-specific risk alleles

Author: Hautakangas, Heidi, Winsvold, Bendik S., Ruotsalainen, Sanni E., Bjornsdottir, Gyda, Harder, Aster V.E., Kogelman, Lisette J.A., Thomas, Laurent F., Noordam, Raymond, Benner, Christian, Gormley, Padhraig, Artto, Ville, Banasik, Karina, Bjornsdottir, Anna, Boomsma, Dorret I., Brumpton, Ben M., Burgdorf, Kristoffer Sølvsten, Buring, Julie E., Chalmer, Mona Ameri, de Boer, Irene, Dichgans, Martin, Erikstrup, Christian, Färkkilä, Markus, Garbrielsen, Maiken Elvestad, Ghanbari, Mohsen, Hagen, Knut, Häppölä, Paavo, Hottenga, Jouke Jan, Hrafnsdottir, Maria G., Hveem, Kristian, Johnsen, Marianne Bakke, Kähönen, Mika, Kristoffersen, Espen S., Kurth, Tobias, Lehtimäki, Terho, Lighart, Lannie, Magnusson, Sigurdur H., Malik, Rainer, Pedersen, Ole Birger, Pelzer, Nadine, Penninx, Brenda W.J.H., Ran, Caroline, Ridker, Paul M., Rosendaal, Frits R., Sigurdardottir, Gudrun R., Skogholt, Anne Heidi, Sveinsson, Olafur A., Thorgeirsson, Thorgeir E., Ullum, Henrik, Vijfhuizen, Lisanne S., Ikram, M. Arfan, Hautakangas, Heidi, Winsvold, Bendik S., Ruotsalainen, Sanni E., Bjornsdottir, Gyda, Harder, Aster V.E., Kogelman, Lisette J.A., Thomas, Laurent F., Noordam, Raymond, Benner, Christian, Gormley, Padhraig, Artto, Ville, Banasik, Karina, Bjornsdottir, Anna, Boomsma, Dorret I., Brumpton, Ben M., Burgdorf, Kristoffer Sølvsten, Buring, Julie E., Chalmer, Mona Ameri, de Boer, Irene, Dichgans, Martin, Erikstrup, Christian, Färkkilä, Markus, Garbrielsen, Maiken Elvestad, Ghanbari, Mohsen, Hagen, Knut, Häppölä, Paavo, Hottenga, Jouke Jan, Hrafnsdottir, Maria G., Hveem, Kristian, Johnsen, Marianne Bakke, Kähönen, Mika, Kristoffersen, Espen S., Kurth, Tobias, Lehtimäki, Terho, Lighart, Lannie, Magnusson, Sigurdur H., Malik, Rainer, Pedersen, Ole Birger, Pelzer, Nadine, Penninx, Brenda W.J.H., Ran, Caroline, Ridker, Paul M., Rosendaal, Frits R., Sigurdardottir, Gudrun R., Skogholt, Anne Heidi, Sveinsson, Olafur A., Thorgeirsson, Thorgeir E., Ullum, Henrik, Vijfhuizen, Lisanne S., and Ikram, M. Arfan
Abstract: Migraine affects over a billion individuals worldwide but its genetic underpinning remains largely unknown. Here, we performed a genome-wide association study of 102,084 migraine cases and 771,257 controls and identified 123 loci, of which 86 are previously unknown. These loci provide an opportunity to evaluate shared and distinct genetic components in the two main migraine subtypes: migraine with aura and migraine without aura. Stratification of the risk loci using 29,679 cases with subtype information indicated three risk variants that seem specific for migraine with aura (in HMOX2, CACNA1A and MPPED2), two that seem specific for migraine without aura (near SPINK2 and near FECH) and nine that increase susceptibility for migraine regardless of subtype. The new risk loci include genes encoding recent migraine-specific drug targets, namely calcitonin gene-related peptide (CALCA/CALCB) and serotonin 1F receptor (HTR1F). Overall, genomic annotations among migraine-associated variants were enriched in both vascular and central nervous system tissue/cell types, supporting unequivocally that neurovascular mechanisms underlie migraine pathophysiology.
Published: 2022

40. Impact of long-term exposure to PM2.5 on peripheral blood gene expression pathways involved in cell signaling and immune response

Author: Planetary Health & Exposoom, Cancer, Circulatory Health, Vlaanderen, Jelle, Vermeulen, Roel, Whitaker, Matthew, Chadeau-Hyam, Marc, Hottenga, Jouke Jan, de Geus, Eco, Willemsen, Gonneke, Penninx, Brenda W.J.H., Jansen, Rick, Boomsma, Dorret I., Planetary Health & Exposoom, Cancer, Circulatory Health, Vlaanderen, Jelle, Vermeulen, Roel, Whitaker, Matthew, Chadeau-Hyam, Marc, Hottenga, Jouke Jan, de Geus, Eco, Willemsen, Gonneke, Penninx, Brenda W.J.H., Jansen, Rick, and Boomsma, Dorret I.
Published: 2022

41. Duration of anxiety disorder and its associated risk indicators: Results of a longitudinal study of the general population

Author: ten Have, Margreet, Tuithof, Marlous, van Dorsselaer, Saskia, Kleinjan, Marloes, Penninx, Brenda W.J.H., Batelaan, Neeltje M., de Graaf, Ron, ten Have, Margreet, Tuithof, Marlous, van Dorsselaer, Saskia, Kleinjan, Marloes, Penninx, Brenda W.J.H., Batelaan, Neeltje M., and de Graaf, Ron
Abstract: Background: Data on episode duration of anxiety disorders are required for informing patients and for disease management, but such data from population studies are lacking. Methods: Three-year longitudinal data were used from the Netherlands Mental Health Survey and Incidence Study-2, a psychiatric epidemiological cohort study among the general adult population (N = 6646). Respondents with a new (first or recurrent) anxiety disorder were selected (n = 158). DSM-IV diagnoses were assessed with the Composite International Diagnostic Interview; the Life Chart Interview assessed episode duration and recovery rates. Results: Among those with anxiety disorder, median episode duration was 7.5 months and mean duration was 15.2 months. 38.8% had not recovered at 12 months and 30.1% not at 36 months. Longer duration was associated with older age, not having a paid job, higher neuroticism, more physical disorders, and worse physical functioning. Conclusions: Also, in the general population, anxiety disorder has a rather chronic course. After 12 months the cumulative recovery rate flattened. To prevent and manage chronicity, timely treatment, and chronic disease management are required. The risk indicators found may help to identify individuals with an anxiety disorder at risk for chronicity.
Published: 2021

42. Examining sex differences in neurodevelopmental and psychiatric genetic risk in anxiety and depression

Author: Martin, Joanna, Asjadi, Kimiya, Hubbard, Leon, Kendall, Kimberley, Pardiñas, Antonio F., Jermy, Bradley, Lewis, Cathryn M., Baune, Bernhard T., Boomsma, Dorret I., Hamilton, Steven P., Lucae, Susanne, Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Mehta, Divya, Mors, Ole, Mullins, Niamh, Penninx, Brenda W.J.H., Preisig, Martin, Rietschel, Marcella, Jones, Ian, Walters, James T.R., Rice, Frances, Thapar, Anita, O'Donovan, Michael, other, and, Martin, Joanna, Asjadi, Kimiya, Hubbard, Leon, Kendall, Kimberley, Pardiñas, Antonio F., Jermy, Bradley, Lewis, Cathryn M., Baune, Bernhard T., Boomsma, Dorret I., Hamilton, Steven P., Lucae, Susanne, Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Mehta, Divya, Mors, Ole, Mullins, Niamh, Penninx, Brenda W.J.H., Preisig, Martin, Rietschel, Marcella, Jones, Ian, Walters, James T.R., Rice, Frances, Thapar, Anita, O'Donovan, Michael, and other, and
Abstract: Anxiety and depression are common mental health disorders and have a higher prevalence in females. They are modestly heritable, share genetic liability with other psychiatric disorders, and are highly heterogeneous. There is evidence that genetic liability to neurodevelopmental disorders, such as attention deficit hyperactivity disorder (ADHD) is associated with anxiety and depression, particularly in females. We investigated sex differences in family history for neurodevelopmental and psychiatric disorders and neurodevelopmental genetic risk burden (indexed by ADHD polygenic risk scores (PRS) and rare copy number variants; CNVs) in individuals with anxiety and depression, also taking into account age at onset. We used two complementary datasets: 1) participants with a self-reported diagnosis of anxiety or depression (N = 4,178, 65.5% female; mean age = 41.5 years; N = 1,315 with genetic data) from the National Centre for Mental Health (NCMH) cohort and 2) a clinical sample of 13,273 (67.6% female; mean age = 45.2 years) patients with major depressive disorder (MDD) from the Psychiatric Genomics Consortium (PGC). We tested for sex differences in family history of psychiatric problems and presence of rare CNVs (neurodevelopmental and >500kb loci) in NCMH only and for sex differences in ADHD PRS in both datasets. In the NCMH cohort, females were more likely to report family history of neurodevelopmental and psychiatric disorders, but there were no robust sex differences in ADHD PRS or presence of rare CNVs. There was weak evidence of higher ADHD PRS in females compared to males in the PGC MDD sample, particularly in those with an early onset of MDD. These results do not provide strong evidence of sex differences in neurodevelopmental genetic risk burden in adults with anxiety and depression. This indicates that sex may not be a major index of neurodevelopmental genetic heterogeneity, that is captured by ADHD PRS and rare CNV burden, in adults with anxiety and depre
Published: 2021

43. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., Medland, Sarah E., Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., and Medland, Sarah E.
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10−8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
Published: 2021
Full Text: View/download PDF

44. Genome-wide association study identifies 48 common genetic variants associated with handedness

Author: Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., Medland, Sarah E., Cuellar-Partida, Gabriel, Tung, Joyce Y., Eriksson, Nicholas, Albrecht, Eva, Aliev, Fazil, Andreassen, Ole A., Barroso, Inês, Beckmann, Jacques S., Boks, Marco P., Boomsma, Dorret I., Boyd, Heather A., Breteler, Monique M.B., Campbell, Harry, Chasman, Daniel I., Cherkas, Lynn F., Davies, Gail, de Geus, Eco J.C., Deary, Ian J., Deloukas, Panos, Dick, Danielle M., Duffy, David L., Eriksson, Johan G., Esko, Tõnu, Feenstra, Bjarke, Geller, Frank, Gieger, Christian, Giegling, Ina, Gordon, Scott D., Han, Jiali, Hansen, Thomas F., Hartmann, Annette M., Hayward, Caroline, Heikkilä, Kauko, Hicks, Andrew A., Hirschhorn, Joel N., Hottenga, Jouke Jan, Huffman, Jennifer E., Hwang, Liang Dar, Ikram, M. Arfan, Kaprio, Jaakko, Kemp, John P., Khaw, Kay Tee, Klopp, Norman, Konte, Bettina, Kutalik, Zoltan, Lahti, Jari, Li, Xin, Loos, Ruth J.F., Luciano, Michelle, Magnusson, Sigurdur H., Mangino, Massimo, Marques-Vidal, Pedro, Martin, Nicholas G., McArdle, Wendy L., McCarthy, Mark I., Medina-Gomez, Carolina, Melbye, Mads, Melville, Scott A., Metspalu, Andres, Milani, Lili, Mooser, Vincent, Nelis, Mari, Nyholt, Dale R., O’Connell, Kevin S., Ophoff, Roel A., Palmer, Cameron, Palotie, Aarno, Palviainen, Teemu, Pare, Guillaume, Paternoster, Lavinia, Peltonen, Leena, Penninx, Brenda W.J.H., Polasek, Ozren, Pramstaller, Peter P., Prokopenko, Inga, Raikkonen, Katri, Ripatti, Samuli, Rivadeneira, Fernando, Rudan, Igor, Rujescu, Dan, Smit, Johannes H., Smith, George Davey, Smoller, Jordan W., Soranzo, Nicole, Spector, Tim D., Pourcain, Beate St, Starr, John M., Stefánsson, Hreinn, Steinberg, Stacy, Teder-Laving, Maris, Thorleifsson, Gudmar, Stefánsson, Kári, Timpson, Nicholas J., Uitterlinden, André G., van Duijn, Cornelia M., van Rooij, Frank J.A., Vink, Jaqueline M., Vollenweider, Peter, Vuoksimaa, Eero, Waeber, Gérard, Wareham, Nicholas J., Warrington, Nicole, Waterworth, Dawn, Werge, Thomas, Wichmann, H. Erich, Widen, Elisabeth, Willemsen, Gonneke, Wright, Alan F., Wright, Margaret J., Xu, Mousheng, Zhao, Jing Hua, Kraft, Peter, Hinds, David A., Lindgren, Cecilia M., Mägi, Reedik, Neale, Benjamin M., Evans, David M., and Medland, Sarah E.
Abstract: Handedness has been extensively studied because of its relationship with language and the over-representation of left-handers in some neurodevelopmental disorders. Using data from the UK Biobank, 23andMe and the International Handedness Consortium, we conducted a genome-wide association meta-analysis of handedness (N = 1,766,671). We found 41 loci associated (P < 5 × 10−8) with left-handedness and 7 associated with ambidexterity. Tissue-enrichment analysis implicated the CNS in the aetiology of handedness. Pathways including regulation of microtubules and brain morphology were also highlighted. We found suggestive positive genetic correlations between left-handedness and neuropsychiatric traits, including schizophrenia and bipolar disorder. Furthermore, the genetic correlation between left-handedness and ambidexterity is low (rG = 0.26), which implies that these traits are largely influenced by different genetic mechanisms. Our findings suggest that handedness is highly polygenic and that the genetic variants that predispose to left-handedness may underlie part of the association with some psychiatric disorders.
Published: 2021

45. Sleep characteristics across the lifespan in 1.1 million people from the Netherlands, United Kingdom and United States: a systematic review and meta-analysis

Author: Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-Verhoeff, M. Elisabeth, Luijk, Maartje P.C.M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., de Bruin, Eduard J., de Graaf, Ron, Derks, Ivonne P.M., Dewald-Kaufmann, Julia F., Elders, Petra J.M., Gemke, Reinoldus J.B.J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W.J.H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, ten Have, Margreet, Twisk, Jos W.R., Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B., van der Velden, Peter G., van Lenthe, Frank J., van Litsenburg, Raphaële R.L., van Oostrom, Sandra H., van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C.M., Vermeulen, Roel C.H., Verschuren, W. M.Monique, Vrijkotte, Tanja G.M., Wijga, Alet H., Willemen, Agnes M., ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J.W., Tiemeier, Henning, Kocevska, Desana, Lysen, Thom S., Dotinga, Aafje, Koopman-Verhoeff, M. Elisabeth, Luijk, Maartje P.C.M., Antypa, Niki, Biermasz, Nienke R., Blokstra, Anneke, Brug, Johannes, Burk, Wiliam J., Comijs, Hannie C., Corpeleijn, Eva, Dashti, Hassan S., de Bruin, Eduard J., de Graaf, Ron, Derks, Ivonne P.M., Dewald-Kaufmann, Julia F., Elders, Petra J.M., Gemke, Reinoldus J.B.J., Grievink, Linda, Hale, Lauren, Hartman, Catharina A., Heijnen, Cobi J., Huisman, Martijn, Huss, Anke, Ikram, M. Arfan, Jones, Samuel E., Velderman, Mariska Klein, Koning, Maaike, Meijer, Anne Marie, Meijer, Kim, Noordam, Raymond, Oldehinkel, Albertine J., Groeniger, Joost Oude, Penninx, Brenda W.J.H., Picavet, H. Susan J., Pieters, Sara, Reijneveld, Sijmen A., Reitz, Ellen, Renders, Carry M., Rodenburg, Gerda, Rutters, Femke, Smith, Matt C., Singh, Amika S., Snijder, Marieke B., Stronks, Karien, ten Have, Margreet, Twisk, Jos W.R., Van de Mheen, Dike, van der Ende, Jan, van der Heijden, Kristiaan B., van der Velden, Peter G., van Lenthe, Frank J., van Litsenburg, Raphaële R.L., van Oostrom, Sandra H., van Schalkwijk, Frank J., Sheehan, Connor M., Verheij, Robert A., Verhulst, Frank C., Vermeulen, Marije C.M., Vermeulen, Roel C.H., Verschuren, W. M.Monique, Vrijkotte, Tanja G.M., Wijga, Alet H., Willemen, Agnes M., ter Wolbeek, Maike, Wood, Andrew R., Xerxa, Yllza, Bramer, Wichor M., Franco, Oscar H., Luik, Annemarie I., Van Someren, Eus J.W., and Tiemeier, Henning
Abstract: We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1–100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40–69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the ‘acceptable’ sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8–10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6–19.4%) were more prevalent than short sleep duration (6.5% with TST <6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending
Published: 2021
Full Text: View/download PDF

46. Metabolomics dissection of depression heterogeneity and related cardiometabolic risk

Author: Alshehri, Tahani, Mook-Kanamori, Dennis O., Dijk, Ko Willems van, Dinga, R., Penninx, Brenda W.J.H., Rosendaal, Frits R., Cessie, Saskia le, Milaneschi, Yuri, Alshehri, Tahani, Mook-Kanamori, Dennis O., Dijk, Ko Willems van, Dinga, R., Penninx, Brenda W.J.H., Rosendaal, Frits R., Cessie, Saskia le, and Milaneschi, Yuri
Abstract: Item does not contain fulltext
Published: 2021

47. Metabolomics dissection of depression heterogeneity and related cardiometabolic risk

Author: Alshehri, Tahani, Mook-Kanamori, Dennis O., Dijk, Ko Willems van, Dinga, R., Penninx, Brenda W.J.H., Rosendaal, Frits R., Cessie, Saskia le, Milaneschi, Yuri, Alshehri, Tahani, Mook-Kanamori, Dennis O., Dijk, Ko Willems van, Dinga, R., Penninx, Brenda W.J.H., Rosendaal, Frits R., Cessie, Saskia le, and Milaneschi, Yuri
Abstract: Item does not contain fulltext
Published: 2021

48. Duration of anxiety disorder and its associated risk indicators: Results of a longitudinal study of the general population

Author: Leerstoel Finkenauer, Youth in Changing Cultural Contexts, ten Have, Margreet, Tuithof, Marlous, van Dorsselaer, Saskia, Kleinjan, Marloes, Penninx, Brenda W.J.H., Batelaan, Neeltje M., de Graaf, Ron, Leerstoel Finkenauer, Youth in Changing Cultural Contexts, ten Have, Margreet, Tuithof, Marlous, van Dorsselaer, Saskia, Kleinjan, Marloes, Penninx, Brenda W.J.H., Batelaan, Neeltje M., and de Graaf, Ron
Published: 2021

49. Educational attainment does not influence brain aging

Author: Nyberg, Lars, Magnussen, Fredrik, Lundquist, Anders, Baaré, William, Bartrés-Faz, David, Bertram, Lars, Boraxbekk, Carl-Johan, Brandmaier, Andreas M., Drevon, Christian A., Ebmeier, Klaus, Ghisletta, Paolo, Henson, Richard N., Junqué, Carme, Kievit, Rogier, Kleemeyer, Maike, Knights, Ethan, Kühn, Simone, Lindenberger, Ulman, Penninx, Brenda W.J.H., Pudas, Sara, Sørensen, Øystein, Vaqué-Alcázar, Lídia, Walhovd, Kristine B., Fjell, Anders M., Nyberg, Lars, Magnussen, Fredrik, Lundquist, Anders, Baaré, William, Bartrés-Faz, David, Bertram, Lars, Boraxbekk, Carl-Johan, Brandmaier, Andreas M., Drevon, Christian A., Ebmeier, Klaus, Ghisletta, Paolo, Henson, Richard N., Junqué, Carme, Kievit, Rogier, Kleemeyer, Maike, Knights, Ethan, Kühn, Simone, Lindenberger, Ulman, Penninx, Brenda W.J.H., Pudas, Sara, Sørensen, Øystein, Vaqué-Alcázar, Lídia, Walhovd, Kristine B., and Fjell, Anders M.
Abstract: Education has been related to various advantageous lifetime outcomes. Here, using longitudinal structural MRI data (4,422 observations), we tested the influential hypothesis that higher education translates into slower rates of brain aging. Cross-sectionally, education was modestly associated with regional cortical volume. However, despite marked mean atrophy in the cortex and hippocampus, education did not influence rates of change. The results were replicated across two independent samples. Our findings challenge the view that higher education slows brain aging.
Published: 2021
Full Text: View/download PDF

50. Educational attainment does not influence brain aging

Author: Nyberg, Lars, Magnussen, Fredrik, Lundquist, Anders, Baaré, William, Bartrés-Faz, David, Bertram, Lars, Boraxbekk, Carl-Johan, Brandmaier, Andreas M., Drevon, Christian A., Ebmeier, Klaus, Ghisletta, Paolo, Henson, Richard N., Junqué, Carme, Kievit, Rogier, Kleemeyer, Maike, Knights, Ethan, Kühn, Simone, Lindenberger, Ulman, Penninx, Brenda W.J.H., Pudas, Sara, Sørensen, Øystein, Vaqué-Alcázar, Lídia, Walhovd, Kristine B., Fjell, Anders M., Nyberg, Lars, Magnussen, Fredrik, Lundquist, Anders, Baaré, William, Bartrés-Faz, David, Bertram, Lars, Boraxbekk, Carl-Johan, Brandmaier, Andreas M., Drevon, Christian A., Ebmeier, Klaus, Ghisletta, Paolo, Henson, Richard N., Junqué, Carme, Kievit, Rogier, Kleemeyer, Maike, Knights, Ethan, Kühn, Simone, Lindenberger, Ulman, Penninx, Brenda W.J.H., Pudas, Sara, Sørensen, Øystein, Vaqué-Alcázar, Lídia, Walhovd, Kristine B., and Fjell, Anders M.
Abstract: Education has been related to various advantageous lifetime outcomes. Here, using longitudinal structural MRI data (4,422 observations), we tested the influential hypothesis that higher education translates into slower rates of brain aging. Cross-sectionally, education was modestly associated with regional cortical volume. However, despite marked mean atrophy in the cortex and hippocampus, education did not influence rates of change. The results were replicated across two independent samples. Our findings challenge the view that higher education slows brain aging.
Published: 2021
Full Text: View/download PDF

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Publication Year Range

Publication Type

Database

Publisher

145 results on '"Penninx, Brenda W.J.H."'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources