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1. Shared genetic basis between genetic generalized epilepsy and background electroencephalographic oscillations

Author

Stevelink, Remi, Luykx, Jurjen J, Lin, Bochao D, Leu, Costin, Lal, Dennis, Smith, Alexander W, Schijven, Dick, Carpay, Johannes A, Rademaker, Koen, Baldez, Roiza A Rodrigues, Devinsky, Orrin, Braun, Kees PJ, Jansen, Floor E, Smit, Dirk JA, Koeleman, Bobby PC, Abou‐Khalil, Bassel, Auce, Pauls, Avbersek, Andreja, Bahlo, Melanie, Balding, David J, Bast, Thomas, Baum, Larry, Becker, Albert J, Becker, Felicitas, Berghuis, Bianca, Berkovic, Samuel F, Boysen, Katja E, Bradfield, Jonathan P, Brody, Lawrence C, Buono, Russell J, Campbell, Ellen, Cascino, Gregory D, Catarino, Claudia B, Cavalleri, Gianpiero L, Cherny, Stacey S, Chinthapalli, Krishna, Coffey, Alison J, Compston, Alastair, Coppola, Antonietta, Cossette, Patrick, Craig, John J, de Haan, Gerrit‐Jan, De Jonghe, Peter, de Kovel, Carolien GF, Delanty, Norman, Depondt, Chantal, Dlugos, Dennis J, Doherty, Colin P, Elger, Christian E, Eriksson, Johan G, Ferraro, Thomas N, Feucht, Martha, Francis, Ben, Franke, Andre, French, Jacqueline A, Freytag, Saskia, Gaus, Verena, Geller, Eric B, Gieger, Christian, Glauser, Tracy, Glynn, Simon, Goldstein, David B, Gui, Hongsheng, Guo, Youling, Haas, Kevin F, Hakonarson, Hakon, Hallmann, Kerstin, Haut, Sheryl, Heinzen, Erin L, Helbig, Ingo, Hengsbach, Christian, Hjalgrim, Helle, Iacomino, Michele, Ingason, Andrés, Jamnadas‐Khoda, Jennifer, Johnson, Michael R, Kälviäinen, Reetta, Kantanen, Anne‐Mari, Kasperavičiūte, Dalia, Trenite, Dorothee Kasteleijn‐Nolst, Kirsch, Heidi E, Knowlton, Robert C, Krause, Roland, Krenn, Martin, Kunz, Wolfram S, Kuzniecky, Ruben, Kwan, Patrick, Lau, Yu‐Lung, Lehesjoki, Anna‐Elina, Lerche, Holger, Lieb, Wolfgang, Lindhout, Dick, Lo, Warren D, Lopes‐Cendes, Iscia, Lowenstein, Daniel H, Malovini, Alberto, Marson, Anthony G, Mayer, Thomas, McCormack, Mark, and Mills, James L

Subjects
Biomedical and Clinical Sciences, Neurosciences, Clinical Sciences, Genetics, Brain Disorders, Clinical Research, Human Genome, Neurodegenerative, Epilepsy, 2.1 Biological and endogenous factors, Aetiology, Neurological, Adult, Algorithms, Beta Rhythm, Cohort Studies, Databases, Factual, Electroencephalography, Epilepsy, Generalized, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Mendelian Randomization Analysis, Risk Assessment, Theta Rhythm, beta power, EEG, generalized epilepsy, GGE, oscillations, PRS, International League Against Epilepsy Consortium on Complex Epilepsies, Epi25 Collaborative, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveParoxysmal epileptiform abnormalities on electroencephalography (EEG) are the hallmark of epilepsies, but it is uncertain to what extent epilepsy and background EEG oscillations share neurobiological underpinnings. Here, we aimed to assess the genetic correlation between epilepsy and background EEG oscillations.MethodsConfounding factors, including the heterogeneous etiology of epilepsies and medication effects, hamper studies on background brain activity in people with epilepsy. To overcome this limitation, we compared genetic data from a genome-wide association study (GWAS) on epilepsy (n = 12 803 people with epilepsy and 24 218 controls) with that from a GWAS on background EEG (n = 8425 subjects without epilepsy), in which background EEG oscillation power was quantified in four different frequency bands: alpha, beta, delta, and theta. We replicated our findings in an independent epilepsy replication dataset (n = 4851 people with epilepsy and 20 428 controls). To assess the genetic overlap between these phenotypes, we performed genetic correlation analyses using linkage disequilibrium score regression, polygenic risk scores, and Mendelian randomization analyses.ResultsOur analyses show strong genetic correlations of genetic generalized epilepsy (GGE) with background EEG oscillations, primarily in the beta frequency band. Furthermore, we show that subjects with higher beta and theta polygenic risk scores have a significantly higher risk of having generalized epilepsy. Mendelian randomization analyses suggest a causal effect of GGE genetic liability on beta oscillations.SignificanceOur results point to shared biological mechanisms underlying background EEG oscillations and the susceptibility for GGE, opening avenues to investigate the clinical utility of background EEG oscillations in the diagnostic workup of epilepsy.

Published
2021

3. Polygenic risk, familial liability and stress reactivity in psychosis: an experience sampling study

Author

Schick, Anita, van Winkel, Ruud, Lin, Bochao D, Luykx, Jurjen J, de Zwarte, Sonja MC, van Eijk, Kristel R, Investigators, Group, Myin-Germeys, Inez, Reininghaus, Ulrich, Psychiatrie & Neuropsychologie, and RS: MHeNs - R2 - Mental Health

Subjects
Psychiatry, MECHANISM, Science & Technology, polygenic risk, stress sensitivity, Psychology, Clinical, ecological momentary assessment, PSYCHOPATHOLOGY, Social Sciences, Digital phenotyping, ASSOCIATION, GENE-ENVIRONMENT INTERACTIONS, gene-environment interaction, CHILDHOOD TRAUMA, Psychiatry and Mental health, DAILY-LIFE, SCHIZOPHRENIA, Psychology, SENSITIVITY, Life Sciences & Biomedicine, PSYCHOLOGICAL PROCESSES, Applied Psychology, SCALE
Abstract

Background There is evidence for a polygenic contribution to psychosis. One targetable mechanism through which polygenic variation may impact on individuals and interact with the social environment is stress sensitization, characterized by elevated reactivity to minor stressors in daily life. The current study aimed to investigate whether stress reactivity is modified by polygenic risk score for schizophrenia (PRS) in cases with enduring non-affective psychotic disorder, first-degree relatives of cases, and controls. Methods We used the experience sampling method to assess minor stressors, negative affect, positive affect and psychotic experiences in 96 cases, 79 first-degree relatives, i.e. siblings, and 73 controls at wave 3 of the Dutch Genetic Risk and Outcome of Psychosis (GROUP) study. Genome-wide data were collected at baseline to calculate PRS. Results We found that associations of momentary stress with psychotic experiences, but not with negative and positive affect, were modified by PRS and group (all pFWEv. low level of PRS. By contrast, controls with high PRS showed more intense psychotic experiences in response to stress compared to those with low PRS. Conclusions This tentatively suggests that polygenic risk may operate in different ways than previously assumed and amplify reactivity to stress in unaffected individuals but operate as a resilience factor in relatives by attenuating their stress reactivity.

Published
2023

4. Gene-environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding

Author

Hersenen-Medisch 1, Onderzoek, Brain, Klingenberg, Boris, Guloksuz, Sinan, Pries, Lotta Katrin, Cinar, Ozan, Menne-Lothmann, Claudia, Decoster, Jeroen, Van Winkel, Ruud, Collip, Dina, Delespaul, Philippe, De Hert, Marc, Derom, Catherine, Thiery, Evert, Jacobs, Nele, Wichers, Marieke, Lin, Bochao D., Luykx, Jurjen, Van Os, Jim, Rutten, Bart P.F., Hersenen-Medisch 1, Onderzoek, Brain, Klingenberg, Boris, Guloksuz, Sinan, Pries, Lotta Katrin, Cinar, Ozan, Menne-Lothmann, Claudia, Decoster, Jeroen, Van Winkel, Ruud, Collip, Dina, Delespaul, Philippe, De Hert, Marc, Derom, Catherine, Thiery, Evert, Jacobs, Nele, Wichers, Marieke, Lin, Bochao D., Luykx, Jurjen, Van Os, Jim, and Rutten, Bart P.F.

Published
2023

5. Associations Between Polygenic Risk Score Loading, Psychosis Liability, and Clozapine Use Among Individuals With Schizophrenia

Author

Hersenen-Medisch 1, Diagnostiek & Vroege Psychose Medisch, Ontwikkelingsstoornissen Med., Onderzoeksgroep 9, Neurogenetica, Onderzoek, Brain, Lin, Bochao D., Pinzón-Espinosa, Justo, Blouzard, Elodie, Van Der Horst, Marte Z., Okhuijsen-Pfeifer, Cynthia, Van Eijk, Kristel R., Guloksuz, Sinan, Peyrot, Wouter J., Luykx, Jurjen J., Hersenen-Medisch 1, Diagnostiek & Vroege Psychose Medisch, Ontwikkelingsstoornissen Med., Onderzoeksgroep 9, Neurogenetica, Onderzoek, Brain, Lin, Bochao D., Pinzón-Espinosa, Justo, Blouzard, Elodie, Van Der Horst, Marte Z., Okhuijsen-Pfeifer, Cynthia, Van Eijk, Kristel R., Guloksuz, Sinan, Peyrot, Wouter J., and Luykx, Jurjen J.

Published
2023

6. Age- and sex-specific associations between risk scores for schizophrenia and self-reported health in the general population

Author

Hersenen-Medisch 1, Neurogenetica, Brain, Paquin, Vincent, Pries, Lotta-Katrin, Ten Have, Margreet, Bak, Maarten, Gunther, Nicole, de Graaf, Ron, van Dorsselaer, Saskia, Lin, Bochao D, van Eijk, Kristel R, Kenis, Gunter, Richards, Alexander, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, van Os, Jim, Shah, Jai L, Guloksuz, Sinan, Hersenen-Medisch 1, Neurogenetica, Brain, Paquin, Vincent, Pries, Lotta-Katrin, Ten Have, Margreet, Bak, Maarten, Gunther, Nicole, de Graaf, Ron, van Dorsselaer, Saskia, Lin, Bochao D, van Eijk, Kristel R, Kenis, Gunter, Richards, Alexander, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, van Os, Jim, Shah, Jai L, and Guloksuz, Sinan

Published
2023

7. Polygenic risk, familial liability and stress reactivity in psychosis: an experience sampling study

Author

Hersenen-Medisch 1, Onderzoek, Brain, Onderzoeksgroep 1, Neurogenetica, Schick, Anita, van Winkel, Ruud, Lin, Bochao D., Luykx, Jurjen J., de Zwarte, Sonja M.C., van Eijk, Kristel R., Reininghaus, Ulrich, Myin-Germeys, Inez, Hersenen-Medisch 1, Onderzoek, Brain, Onderzoeksgroep 1, Neurogenetica, Schick, Anita, van Winkel, Ruud, Lin, Bochao D., Luykx, Jurjen J., de Zwarte, Sonja M.C., van Eijk, Kristel R., Reininghaus, Ulrich, and Myin-Germeys, Inez

Published
2023

8. Context v. algorithm: Evidence that a transdiagnostic framework of contextual clinical characterization is of more clinical value than categorical diagnosis

Author

Hersenen-Medisch 1, Brain, TN groep Adan, Onderzoek, Neurogenetica, Van Os, Jim, Pries, Lotta Katrin, Ten Have, Margreet, De Graaf, Ron, Van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D., Gunther, Nicole, Luykx, Jurjen J., Rutten, Bart P.F., Guloksuz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, Onderzoek, Neurogenetica, Van Os, Jim, Pries, Lotta Katrin, Ten Have, Margreet, De Graaf, Ron, Van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D., Gunther, Nicole, Luykx, Jurjen J., Rutten, Bart P.F., and Guloksuz, Sinan

Published
2023

9. Gene–environment interaction study on the polygenic risk score for neuroticism, childhood adversity, and parental bonding

Author

Klingenberg, Boris, primary, Guloksuz, Sinan, additional, Pries, Lotta-Katrin, additional, Cinar, Ozan, additional, Menne-Lothmann, Claudia, additional, Decoster, Jeroen, additional, van Winkel, Ruud, additional, Collip, Dina, additional, Delespaul, Philippe, additional, De Hert, Marc, additional, Derom, Catherine, additional, Thiery, Evert, additional, Jacobs, Nele, additional, Wichers, Marieke, additional, Lin, Bochao D., additional, Luykx, Jurjen, additional, van Os, Jim, additional, and Rutten, Bart P. F., additional

Published
2023
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10. Examining the association between exposome score for schizophrenia and cognition in schizophrenia, siblings, and healthy controls: Results from the EUGEI study

Author

Bobes, Julio, Fusar-Poli, Laura, Prachason, Thanavadee, Erzin, Gamze, Pries, Lotta-Katrin, Brondino, Natascia, Politi, Pierluigi, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Andric-Petrovic, Sanja, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Saka, Meram Can, Alptekin, Köksal, Üçok, Alp, Atbaşoğlu, Cem, Maric, Nadja P, Parellada, Mara, González-Peñas, Javier, López, Gonzalo, Carracedo, Angel, Arrojo, Manuel, Jiménez-López, Estela, Santos, José Luis, Escarti, Maria Jose, Sanjuan, Julio, García-Portilla, Maria Paz, Saiz, Pilar A, Amoretti, Silvia, Guloksuz, Sinan, Rutten, Bart PF, van Os, Jim, O'Donovan, Michael, and Arango, Celso

Subjects
Psychiatry and Mental health, Biological Psychiatry
Abstract

Background: People with schizophrenia spectrum disorders (SSD) frequently present cognitive impairments. Here, we investigated whether the exposome score for schizophrenia (ES-SCZ) - a cumulative environmental exposure score - was associated with impairments of neurocognition, social cognition, and perception in patients with SSD, their unaffected siblings, and healthy controls. Methods: This cross-sectional sample consisted of 1200 patients, 1371 siblings, and 1564 healthy controls. Neurocognition, social cognition, and perception were assesed using a short version of the Wechsler Adult Intelligence Scale–Third Edition (WAIS-III), the Degraded Facial Affect Recognition Task (DFAR), and the Benton Facial Recognition Test (BFR), respectively. Regression models were used to analyze the association between ES-SCZ and cognitive domains in each group. Results: There were no statistically significant associations between ES-SCZ and cognitive domains in SSD. ES-SCZ was negatively associated with T-score of cognition in siblings (B=-0.40, 95% CI -0.76 to -0.03) and healthy controls (B=-0.63, 95% CI -1.06 to -0.21). Additionally, ES-SCZ was positively associated with DFAR-total in siblings (B=0.83, 95% CI 0.26 to 1.40). Sensitivity analyses excluding cannabis use history from ES-SCZ largely confirmed the main findings. Conclusions: Longitudinal cohorts may elucidate how environmental exposures influence the onset and course of cognitive impairments in trans-syndromic psychosis spectrum.

Published
2023

11. A polygenic-informed approach to a predictive EEG signature empowers antidepressant treatment prediction: A proof-of-concept study

Author

AIOS Psychiatrie, Hersenen-Medisch 1, Neurogenetica, Meijs, Hannah, Prentice, Amourie, Lin, Bochao D., De Wilde, Bieke, Van Hecke, Jan, Niemegeers, Peter, van Eijk, Kristel, Luykx, Jurjen J., Arns, Martijn, AIOS Psychiatrie, Hersenen-Medisch 1, Neurogenetica, Meijs, Hannah, Prentice, Amourie, Lin, Bochao D., De Wilde, Bieke, Van Hecke, Jan, Niemegeers, Peter, van Eijk, Kristel, Luykx, Jurjen J., and Arns, Martijn

Published
2022

12. Evidence, and replication thereof, that molecular-genetic and environmental risks for psychosis impact through an affective pathway

Author

Hersenen-Medisch 1, Brain, TN groep Adan, van Os, Jim, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Delespaul, Philippe, Bak, Maarten, Kenis, Gunter, Lin, Bochao D, Luykx, Jurjen J, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Guloksuz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, van Os, Jim, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Delespaul, Philippe, Bak, Maarten, Kenis, Gunter, Lin, Bochao D, Luykx, Jurjen J, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, and Guloksuz, Sinan

Published
2022

13. A replication study of JTC bias, genetic liability for psychosis and delusional ideation

Author

Hersenen-Medisch 1, Brain, TN groep Adan, Laboranten CT Radiologie, Henquet, Cécile, van Os, Jim, Pries, Lotta K, Rauschenberg, Christian, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem S, Kaymak, Semra U, Mihaljevic, Marina M, Petrovic, Sanja S, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria P, Sanjuan, Julio, Aguilar, Eduardo J, Santos, Jose L, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram C, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Gülöksüz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, Laboranten CT Radiologie, Henquet, Cécile, van Os, Jim, Pries, Lotta K, Rauschenberg, Christian, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem S, Kaymak, Semra U, Mihaljevic, Marina M, Petrovic, Sanja S, Mirjanic, Tijana, Bernardo, Miguel, Mezquida, Gisela, Amoretti, Silvia, Bobes, Julio, Saiz, Pilar A, García-Portilla, Maria P, Sanjuan, Julio, Aguilar, Eduardo J, Santos, Jose L, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram C, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, and Gülöksüz, Sinan

Published
2022

14. Examining the independent and joint effects of molecular genetic liability and environmental exposures in schizophrenia

Author

Guloksuz, Sinan, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altinyazar, Vesile, Yalinçetin, Berna, Gümüs-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulas, Halis, Cankurtaran, EylemSahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbasoglu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P.F., van Os, Jim, Alizadeh, Behrooz Z., van Amelsvoort, Therese, van Beveren, Nico J., Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, Myin?Germeys, Inez, van Winkel, Ruud, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Germeys, I, van Winkel, Ruud, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Promovendi MHN, MUMC+: MA Niet Med Staf Psychiatrie (9), RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), MUMC+: Hersen en Zenuw Centrum (3), and MUMC+: MA Med Staf Spec Psychiatrie (9)

Subjects
cannabis, Psychosis, medicine.medical_specialty, polygenic risk, Season of birth, DISORDERS, VALIDATION, 03 medical and health sciences, 0302 clinical medicine, PSYCHOSIS, Journal Article, medicine, IMPUTATION, genetics, Gene–environment interaction, Psychological abuse, Psychiatry, Science & Technology, childhood trauma, INSTRUMENT, biology, business.industry, HERITABILITY, Research Reports, ASSOCIATION, medicine.disease, biology.organism_classification, 030227 psychiatry, gene-environment interaction, Psychiatry and Mental health, Physical abuse, Sexual abuse, bullying, RELIABILITY, Schizophrenia, Phychiatric Mental Health, Cannabis, Pshychiatric Mental Health, business, Life Sciences & Biomedicine, environment, 030217 neurology & neurosurgery, Diagnosis of schizophrenia
Abstract

Schizophrenia is a heritable complex phenotype associated with a background risk involving multiple common genetic variants of small effect and a multitude of environmental exposures. Early twin and family studies using proxy-genetic liability measures suggest gene-environment interaction in the etiology of schizophrenia spectrum disorders, but the molecular evidence is scarce. Here, by analyzing the main and joint associations of polygenic risk score for schizophrenia (PRS-SCZ) and environmental exposures in 1,699 patients with a diagnosis of schizophrenia spectrum disorders and 1,542 unrelated controls with no lifetime history of a diagnosis of those disorders, we provide further evidence for gene-environment interaction in schizophrenia. Evidence was found for additive interaction of molecular genetic risk state for schizophrenia (binary mode of PRS-SCZ above 75% of the control distribution) with the presence of lifetime regular cannabis use and exposure to early-life adversities (sexual abuse, emotional abuse, emotional neglect, and bullying), but not with the presence of hearing impairment, season of birth (winter birth), and exposure to physical abuse or physical neglect in childhood. The sensitivity analyses replacing the a priori PRS-SCZ at 75% with alternative cut-points (50% and 25%) confirmed the additive interaction. Our results suggest that the etiopathogenesis of schizophrenia involves genetic underpinnings that act by making individuals more sensitive to the effects of some environmental exposures. ispartof: WORLD PSYCHIATRY vol:18 issue:2 pages:173-182 ispartof: location:Italy status: published

Published
2019

16. What makes the psychosis 'clinical high risk' state risky: psychosis itself or the co-presence of a non-psychotic disorder?

Author

Hersenen-Medisch 1, Brain, Hasmi, Laila, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Richards, Alexander, Lin, Bochao D, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, van Os, Jim, Hersenen-Medisch 1, Brain, Hasmi, Laila, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Richards, Alexander, Lin, Bochao D, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, and van Os, Jim

Published
2021

17. Erratum:Associations between psychiatric disorders, COVID-19 testing probability and COVID-19 testing results: Findings from a population-based study (BJPsych Open (2020) 6:5 (e87) DOI: 10.1192/bjo.2020.75)

Author

van der Meer, Dennis, Pinzón-Espinosa, Justo, Lin, Bochao D., Tijdink, Joeri K., Vinkers, Christiaan H., Guloksuz, Sinan, and Luykx, Jurjen J.

Abstract

This article failed to state the coequal contribution to the article of its first two authors, Dennis van der Meer and Justo Pinz n- Espinosa. This note was deleted accidentally during the production process, for which the publisher apologises.

Published
2020

18. A new genetic locus for antipsychotic-induced weight gain:A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Author

ter Hark, Sophie E., Jamain, Stéphane, Schijven, Dick, Lin, Bochao D., Bakker, Mark K., Boland-Auge, Anne, Deleuze, Jean François, Troudet, Réjane, Malhotra, Anil K., Gülöksüz, Sinan, Vinkers, Christiaan H., Ebdrup, Bjørn H., Kahn, René S., Leboyer, Marion, Luykx, Jurjen J., ter Hark, Sophie E., Jamain, Stéphane, Schijven, Dick, Lin, Bochao D., Bakker, Mark K., Boland-Auge, Anne, Deleuze, Jean François, Troudet, Réjane, Malhotra, Anil K., Gülöksüz, Sinan, Vinkers, Christiaan H., Ebdrup, Bjørn H., Kahn, René S., Leboyer, Marion, and Luykx, Jurjen J.

Abstract

Background: Antipsychotic-induced weight gain is a common and debilitating side effect of antipsychotics. Although genome-wide association studies of antipsychotic-induced weight gain have been performed, few genome-wide loci have been discovered. Moreover, these genome-wide association studies have included a wide variety of antipsychotic compounds. Aims: We aim to gain more insight in the genomic loci affecting antipsychotic-induced weight gain. Given the variable pharmacological properties of antipsychotics, we hypothesized that targeting a single antipsychotic compound would provide new clues about genomic loci affecting antipsychotic-induced weight gain. Methods: All subjects included for this genome-wide association study (n=339) were first-episode schizophrenia spectrum disorder patients treated with amisulpride and were minimally medicated (defined as antipsychotic use <2 weeks in the previous year and/or <6 weeks lifetime). Weight gain was defined as the increase in body mass index from before until approximately 1 month after amisulpride treatment. Results: Our genome-wide association analyses for antipsychotic-induced weight gain yielded one genome-wide significant hit (rs78310016; β=1.05; p=3.66 × 10−08; n=206) in a locus not previously associated with antipsychotic-induced weight gain or body mass index. Minor allele carriers had an odds ratio of 3.98 (p=1.0 × 10−03) for clinically meaningful antipsychotic-induced weight gain (⩾7% of baseline weight). In silico analysis elucidated a chromatin interaction with 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1. In an attempt to replicate single-nucleotide polymorphisms previously associated with antipsychotic-induced weight gain, we found none were associated with amisulpride-induced weight gain. Conclusion: Our findings suggest the involvement of rs78310016 and possibly 3-Hydroxy-3-Methylglutaryl-CoA Synthase 1 in antipsychotic-induced weight gain. In line with the unique binding p

Published
2020

19. Do Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health?

Author

TN groep Adan, Hersenen-Medisch 1, Brain, Marsman, Anne, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, van Os, Jim, TN groep Adan, Hersenen-Medisch 1, Brain, Marsman, Anne, Pries, Lotta-Katrin, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Kenis, Gunter, Lin, Bochao D, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, and van Os, Jim

Published
2020

20. Association of Recent Stressful Life Events With Mental and Physical Health in the Context of Genomic and Exposomic Liability for Schizophrenia

Author

Hersenen-Medisch 1, Brain, TN groep Adan, Neurogenetica, Pries, Lotta-Katrin, van Os, Jim, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Lin, Bochao D, van Eijk, Kristel R, Kenis, Gunter, Richards, Alexander, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, Guloksuz, Sinan, Hersenen-Medisch 1, Brain, TN groep Adan, Neurogenetica, Pries, Lotta-Katrin, van Os, Jim, Ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Bak, Maarten, Lin, Bochao D, van Eijk, Kristel R, Kenis, Gunter, Richards, Alexander, O'Donovan, Michael C, Luykx, Jurjen J, Rutten, Bart P F, and Guloksuz, Sinan

Published
2020

21. Association of preceding psychosis risk states and non-psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS-2 cohort

Author

Neurogenetica, Brain, Hersenen-Medisch 1, Guloksuz, Sinan, Pries, Lotta Katrin, ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Klingenberg, Boris, Bak, Maarten, Lin, Bochao D, van Eijk, Kristel R., Delespaul, Philippe, van Amelsvoort, Therese, Luykx, Jurjen J., Rutten, Bart P.F., van Os, Jim, Neurogenetica, Brain, Hersenen-Medisch 1, Guloksuz, Sinan, Pries, Lotta Katrin, ten Have, Margreet, de Graaf, Ron, van Dorsselaer, Saskia, Klingenberg, Boris, Bak, Maarten, Lin, Bochao D, van Eijk, Kristel R., Delespaul, Philippe, van Amelsvoort, Therese, Luykx, Jurjen J., Rutten, Bart P.F., and van Os, Jim

Published
2020

22. A new genetic locus for antipsychotic-induced weight gain: A genome-wide study of first-episode psychosis patients using amisulpride (from the OPTiMiSE cohort)

Author

Neurogenetica, Brain, TN groep Adan, MS Neonatologie, Onderzoeksgroep 11, Ter Hark, Sophie E, Jamain, Stéphane, Schijven, Dick, Lin, Bochao D, Bakker, Mark K, Boland-Auge, Anne, Deleuze, Jean-François, Troudet, Réjane, Malhotra, Anil K, Gülöksüz, Sinan, Vinkers, Christiaan H, Ebdrup, Bjørn H, Kahn, René S, Leboyer, Marion, Luykx, Jurjen J, Neurogenetica, Brain, TN groep Adan, MS Neonatologie, Onderzoeksgroep 11, Ter Hark, Sophie E, Jamain, Stéphane, Schijven, Dick, Lin, Bochao D, Bakker, Mark K, Boland-Auge, Anne, Deleuze, Jean-François, Troudet, Réjane, Malhotra, Anil K, Gülöksüz, Sinan, Vinkers, Christiaan H, Ebdrup, Bjørn H, Kahn, René S, Leboyer, Marion, and Luykx, Jurjen J

Published
2020

23. Replicated evidence that endophenotypic expression of schizophrenia polygenic risk is greater in healthy siblings of patients compared to controls, suggesting gene-environment interaction. The EUGEI study

Author

Brain, Hersenen-Medisch 1, Neurogenetica, TN groep Adan, van Os, Jim, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Guloksuz, Sinan, Genetic Risk and Outcome Investigators (GROUP), Brain, Hersenen-Medisch 1, Neurogenetica, TN groep Adan, van Os, Jim, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, O'Donovan, Michael, Rutten, Bart P F, Guloksuz, Sinan, and Genetic Risk and Outcome Investigators (GROUP)

Published
2020

24. What makes the psychosis ‘clinical high risk’ state risky: psychosis itself or the co-presence of a non-psychotic disorder?

Author

Hasmi, Laila, primary, Pries, Lotta-Katrin, additional, ten Have, Margreet, additional, de Graaf, Ron, additional, van Dorsselaer, Saskia, additional, Bak, Maarten, additional, Kenis, Gunter, additional, Richards, Alexander, additional, Lin, Bochao D., additional, O'Donovan, Michael C., additional, Luykx, Jurjen J., additional, Rutten, Bart P.F., additional, Guloksuz, Sinan, additional, and van Os, Jim, additional

Published
2021
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26. Do Current Measures of Polygenic Risk for Mental Disorders Contribute to Population Variance in Mental Health?

Author

Marsman, Anne, primary, Pries, Lotta-Katrin, additional, ten Have, Margreet, additional, de Graaf, Ron, additional, van Dorsselaer, Saskia, additional, Bak, Maarten, additional, Kenis, Gunter, additional, Lin, Bochao D, additional, Luykx, Jurjen J, additional, Rutten, Bart P F, additional, Guloksuz, Sinan, additional, and van Os, Jim, additional

Published
2020
Full Text
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27. Association of preceding psychosis risk states and non‐psychotic mental disorders with incidence of clinical psychosis in the general population: a prospective study in the NEMESIS‐2 cohort

Author

Guloksuz, Sinan, primary, Pries, Lotta‐Katrin, additional, Have, Margreet, additional, Graaf, Ron, additional, Dorsselaer, Saskia, additional, Klingenberg, Boris, additional, Bak, Maarten, additional, Lin, Bochao D., additional, Eijk, Kristel R., additional, Delespaul, Philippe, additional, Amelsvoort, Therese, additional, Luykx, Jurjen J., additional, Rutten, Bart P.F., additional, and Os, Jim, additional

Published
2020
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28. Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study

Author

Pries, Lotta-Katrin, Lage-Castellanos, Agustin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J, Lin, Bochao D, Richards, Alexander L, Akdede, Berna, Binbay, Tolga, Altinyazar, Vesile, Yalinçetin, Berna, Gümüs-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ula?, Halis, Cankurtaran, Eylem ?ahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M, Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A, García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J, Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P, Atba?o?lu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Alizadeh, Behrooz Z, van Amelsvoort, Therese, Bruggeman, Richard, Cahn, Wiepke, de Haan, Lieuwe, van Winkel, Ruud, Rutten, Bart P F, van Os, Jim, Arango, Celso, O'Donovan, Michael, Guloksuz, Sinan, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Perceptual and Cognitive Neuroscience (PCN), Life Course Epidemiology (LCE), Clinical Cognitive Neuropsychiatry Research Program (CCNP), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Promovendi MHN, Psychiatrie & Neuropsychologie, RS: MHeNs - R2 - Mental Health, Audition, RS: FPN CN 2, MUMC+: MA Niet Med Staf Psychiatrie (9), RS: MHeNs - R3 - Neuroscience, MUMC+: MA Psychiatrie (3), and RS: MHeNs School for Mental Health and Neuroscience

Subjects
Male, cannabis, Logistic regression, 0302 clinical medicine, Lasso (statistics), Adverse Childhood Experiences, Statistics, Odds Ratio, Child Abuse, POLYGENIC RISK, psychosis, Child, Psychiatry, SUMMER BIRTH, Framingham Risk Score, 3. Good health, Exposome, Psychiatry and Mental health, machine learning, Schizophrenia, Area Under Curve, Female, Marijuana Use, Seasons, Environment And Schizophrenia—Feature Editor: Jim van Os, Life Sciences & Biomedicine, environment, predictive modeling, Adult, DISORDERS, risk score, Young Adult, 03 medical and health sciences, PSYCHOSIS, medicine, Journal Article, Humans, Hearing Loss, METAANALYSIS, DEFICIT SCHIZOPHRENIA, ENVIRONMENT, Models, Statistical, Science & Technology, childhood trauma, Receiver operating characteristic, business.industry, Siblings, Bullying, Bayes Theorem, Child Abuse, Sexual, Odds ratio, hearing impairment, medicine.disease, 030227 psychiatry, schizophrenia, Logistic Models, ROC Curve, Sexual abuse, Case-Control Studies, business, CHILDHOOD ADVERSITIES, 030217 neurology & neurosurgery, winter birth
Abstract

The EUGEI project was supported by the grant agreement HEALTH-F2-2010-241909 from the European Community’s Seventh Framework Programme. The authors are grateful to the patients and their families for participating in the project. They also thank all research personnel involved in the GROUP project, in particular J. van Baaren, E. Veermans, G. Driessen, T. Driesen, E. van’t Hag and J. de Nijs. Bart PF Rutten was funded by a VIDI award number 91718336 from the Netherlands Scientific Organisation., Pries, L.-K., Lage-Castellanos, A., Delespaul, P., Kenis, G., Luykx, J.J., Lin, B.D., Richards, A.L., Akdede, B., Binbay, T., Altinyazar, V., Yalinçetin, B., Gümüş-Akay, G., Cihan, B., Soygür, H., Ulaş, H., Cankurtaran, E.Ş., Kaymak, S.U., Mihaljevic, M.M., Petrovic, S.A., Mirjanic, T., Bernardo, M., Cabrera, B., Bobes, J., Saiz, P.A., García-Portilla, M.P., Sanjuan, J., Aguilar, E.J., Santos, J.L., Jiménez-López, E., Arrojo, M., Carracedo, A., López, G., González-Peñas, J., Parellada, M., Maric, N.P., Atbaşoğlu, C., Ucok, A., Alptekin, K., Saka, M.C., Arango, C., O'Donovan, M., Rutten, B.P.F., van Os, J., Guloksuz, S.

Published
2019

29. Assessing causal links between metabolic traits, inflammation and schizophrenia : a univariable and multivariable, bidirectional Mendelian-randomization study

Author

Lin, Bochao D., Alkema, Anne, Peters, Triinu, Zinkstok, Janneke, Libuda, Lars, Hebebrand, Johannes, Antel, Jochen, Hinney, Anke, Cahn, Wiepke, Adan, Roger, Luykx, Jurjen J., Lin, Bochao D., Alkema, Anne, Peters, Triinu, Zinkstok, Janneke, Libuda, Lars, Hebebrand, Johannes, Antel, Jochen, Hinney, Anke, Cahn, Wiepke, Adan, Roger, and Luykx, Jurjen J.

Published
2019

30. White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?

Author

Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altinyazar, Vesile, Yalincetin, Berna, Gumus-Akay, Guvem, Cihan, Burcin, Soygur, Haldun, Ulas, Halis, Cankurtaran, Eylem Sahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., Paz Garcia-Portilla, Maria, Sanjuan, Julio, Aguilar, Eduardo J., Luis Santos, Jose, Jimenez-Lopez, Estela, Arrojo, Manuel, Carracedo, Angel, Lopez, Gonzalo, Gonzalez-Penas, Javier, Parellada, Mara, Maric, Nadja P., Atbasoglu, Cem, Ucok, Alp, Alptekin, Koksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P. F., van Os, Jim, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta-Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altinyazar, Vesile, Yalincetin, Berna, Gumus-Akay, Guvem, Cihan, Burcin, Soygur, Haldun, Ulas, Halis, Cankurtaran, Eylem Sahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., Paz Garcia-Portilla, Maria, Sanjuan, Julio, Aguilar, Eduardo J., Luis Santos, Jose, Jimenez-Lopez, Estela, Arrojo, Manuel, Carracedo, Angel, Lopez, Gonzalo, Gonzalez-Penas, Javier, Parellada, Mara, Maric, Nadja P., Atbasoglu, Cem, Ucok, Alp, Alptekin, Koksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P. F., and van Os, Jim

Published
2019

31. Assessing causal links between metabolic traits, inflammation and schizophrenia: a univariable and multivariable, bidirectional Mendelian-randomization study

Author

TN groep Adan, AIOS Psychiatrie, Affectieve & Psychotische Med., Onderzoek, Brain, Circulatory Health, Neurogenetica, Lin, Bochao D., Alkema, Anne, Peters, Triinu, Zinkstok, Janneke, Libuda, Lars, Hebebrand, Johannes, Antel, Jochen, Hinney, Anke, Cahn, Wiepke, Adan, Roger, Luykx, Jurjen J., TN groep Adan, AIOS Psychiatrie, Affectieve & Psychotische Med., Onderzoek, Brain, Circulatory Health, Neurogenetica, Lin, Bochao D., Alkema, Anne, Peters, Triinu, Zinkstok, Janneke, Libuda, Lars, Hebebrand, Johannes, Antel, Jochen, Hinney, Anke, Cahn, Wiepke, Adan, Roger, and Luykx, Jurjen J.

Published
2019

32. White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?

Author

Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Semra, Ulusoy Kaymak, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez López, Estela, Arrojo Romero, Manuel, Carracedo Álvarez, Ángel María, López, Gonzalo, González Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P.F., Os, Jim van, Universidade de Santiago de Compostela. Departamento de Psiquiatría, Radioloxía, Saúde Pública, Enfermaría e Medicina, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Semra, Ulusoy Kaymak, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez López, Estela, Arrojo Romero, Manuel, Carracedo Álvarez, Ángel María, López, Gonzalo, González Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P.F., and Os, Jim van

Abstract

Introduction: White noise speech illusions index liability for psychotic disorder in case–control comparisons. In the current study, we examined i) the rate of white noise speech illusions in siblings of patients with psychotic disorder and ii) to what degree this rate would be contingent on exposure to known environmental risk factors (childhood adversity and recent life events) and level of known endophenotypic dimensions of psychotic disorder [psychotic experiences assessed with the Community Assessment of Psychic Experiences (CAPE) scale and cognitive ability]. Methods: The white noise task was used as an experimental paradigm to elicit and measure speech illusions in 1,014 patients with psychotic disorders, 1,157 siblings, and 1,507 healthy participants. We examined associations between speech illusions and increasing familial risk (control -> sibling -> patient), modeled as both a linear and a categorical effect, and associations between speech illusions and level of childhood adversities and life events as well as with CAPE scores and cognitive ability scores. Results: While a positive association was found between white noise speech illusions across hypothesized increasing levels of familial risk (controls -> siblings -> patients) [odds ratio (OR) linear 1.11, 95% confidence interval (CI) 1.02–1.21, p = 0.019], there was no evidence for a categorical association with sibling status (OR 0.93, 95% CI 0.79–1.09, p = 0.360). The association between speech illusions and linear familial risk was greater if scores on the CAPE positive scale were higher (p interaction = 0.003; ORlow CAPE positive scale 0.96, 95% CI 0.85–1.07; ORhigh CAPE positive scale 1.26, 95% CI 1.09–1.46); cognitive ability was lower (p interaction < 0.001; ORhigh cognitive ability 0.94, 95% CI 0.84–1.05; ORlow cognitive ability 1.43, 95% CI 1.23–1.68); and exposure to childhood adversity was higher (p interaction < 0.001; ORlow adversity 0.92, 95% CI 0.82–1.04; ORhigh adversity 1.31, 95% CI 1.1

Published
2019

33. White noise speech illusions: A trait-dependent risk marker for psychotic disorder?

Author

Brain, Neurogenetica, TN groep Adan, Hersenen-Medisch 1, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P.F., van Os, Jim, Brain, Neurogenetica, TN groep Adan, Hersenen-Medisch 1, Schepers, Elaine, Lousberg, Richel, Guloksuz, Sinan, Pries, Lotta Katrin, Delespaul, Philippe, Kenis, Gunter, Luykx, Jurjen J., Lin, Bochao D., Richards, Alexander L., Akdede, Berna, Binbay, Tolga, Altınyazar, Vesile, Yalınçetin, Berna, Gümüş-Akay, Güvem, Cihan, Burçin, Soygür, Haldun, Ulaş, Halis, Cankurtaran, Eylem Şahin, Kaymak, Semra Ulusoy, Mihaljevic, Marina M., Petrovic, Sanja Andric, Mirjanic, Tijana, Bernardo, Miguel, Cabrera, Bibiana, Bobes, Julio, Saiz, Pilar A., García-Portilla, María Paz, Sanjuan, Julio, Aguilar, Eduardo J., Santos, José Luis, Jiménez-López, Estela, Arrojo, Manuel, Carracedo, Angel, López, Gonzalo, González-Peñas, Javier, Parellada, Mara, Maric, Nadja P., Atbaşoğlu, Cem, Ucok, Alp, Alptekin, Köksal, Saka, Meram Can, Arango, Celso, Rutten, Bart P.F., and van Os, Jim

Published
2019

34. Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability

Author

Valdes, Ana M., Hysi, Pirro G., Liu, Fan, Furlotte, Nicholas A., Evans, David M., Bataille, Veronique, Visconti, Alessia, Hemani, Gibran, McMahon, George, Ring, Susan M., Smith, George Davey, Duffy, David L., Zhu, Gu, Gordon, Scott D., Medland, Sarah E., Lin, Bochao D., Willemsen, Gonneke, Hottenga, Jouke Jan, Vuckovic, Dragana, Girotto, Giorgia, Gandin, Ilaria, Sala, Cinzia, Pina Concas, Maria, Brumat, Marco, Gasparini, Paolo, Toniolo, Daniela, Cocca, Massimiliano, Robino, Antonietta, Yazar, Seyhan, Hewitt, Alex W., Chen, Yan, Zeng, Changqing, Uitterlinden, Andre G., Arfan Ikram, M., Hamer, Merel A., van Duijn, Cornelia M., Nijsten, Tamar, Mackey, David A., Falchi, Mario, Boomsma, Dorret I., Martin, Nicholas G., Hinds, David A., Kayser, Manfred, Spector, Timothy D., and International Visible Trait Genetics Consortium

Subjects
integumentary system, sense organs
Abstract

© 2018 The Author(s). Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but 13 are novel. Collectively, single-nucleotide polymorphisms associated with hair color within these loci explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study populations. These results confirm the polygenic nature of complex phenotypes and improve our understanding of melanin pigment metabolism in humans.

Published
2018

35. White Noise Speech Illusions: A Trait-Dependent Risk Marker for Psychotic Disorder?

Author

Schepers, Elaine, primary, Lousberg, Richel, additional, Guloksuz, Sinan, additional, Pries, Lotta-Katrin, additional, Delespaul, Philippe, additional, Kenis, Gunter, additional, Luykx, Jurjen J., additional, Lin, Bochao D., additional, Richards, Alexander L., additional, Akdede, Berna, additional, Binbay, Tolga, additional, Altınyazar, Vesile, additional, Yalınçetin, Berna, additional, Gümüş-Akay, Güvem, additional, Cihan, Burçin, additional, Soygür, Haldun, additional, Ulaş, Halis, additional, Şahin Cankurtaran, Eylem, additional, Ulusoy Kaymak, Semra, additional, Mihaljevic, Marina M., additional, Andric Petrovic, Sanja, additional, Mirjanic, Tijana, additional, Bernardo, Miguel, additional, Cabrera, Bibiana, additional, Bobes, Julio, additional, Saiz, Pilar A., additional, García-Portilla, María Paz, additional, Sanjuan, Julio, additional, Aguilar, Eduardo J., additional, Luis Santos, José, additional, Jiménez-López, Estela, additional, Arrojo, Manuel, additional, Carracedo, Angel, additional, López, Gonzalo, additional, González-Peñas, Javier, additional, Parellada, Mara, additional, Maric, Nadja P., additional, Atbaşoğlu, Cem, additional, Ucok, Alp, additional, Alptekin, Köksal, additional, Can Saka, Meram, additional, Arango, Celso, additional, Rutten, Bart P.F., additional, and van Os, Jim, additional

Published
2019
Full Text
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37. Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability

Author

Hysi, Pirro G., Valdes, Ana M., Liu, Fan, Furlotte, Nicholas A., Evans, David M., Bataille, Veronique, Visconti, Alessia, Hemani, Gibran, McMahon, George, Ring, Susan M., Smith, George Davey, Duffy, David L., Zhu, Gu, Gordon, Scott D., Medland, Sarah E., Lin, Bochao D., Willemsen, Gonneke, Hottenga, Jouke Jan, Vuckovic, Dragana, Girotto, Giorgia, Gandin, Ilaria, Sala, Cinzia, Concas, Maria Pina, Brumat, Marco, Gasparini, Paolo, Toniolo, Daniela, Cocca, Massimiliano, Robino, Antonietta, Yazar, Seyhan, Hewitt, Alex W., Chen, Yan, Zeng, Changqing, Uitterlinden, Andre G., Ikram, M. Arfan, Hamer, Merel A., Van Duijn, Cornelia M., Nijsten, Tamar, MacKey, David A., Falchi, Mario, Boomsma, Dorret I., Martin, Nicholas G., Hinds, David A., Kayser, Manfred, Spector, Timothy D., Hysi, Pirro G., Valdes, Ana M., Liu, Fan, Furlotte, Nicholas A., Evans, David M., Bataille, Veronique, Visconti, Alessia, Hemani, Gibran, McMahon, George, Ring, Susan M., Smith, George Davey, Duffy, David L., Zhu, Gu, Gordon, Scott D., Medland, Sarah E., Lin, Bochao D., Willemsen, Gonneke, Hottenga, Jouke Jan, Vuckovic, Dragana, Girotto, Giorgia, Gandin, Ilaria, Sala, Cinzia, Concas, Maria Pina, Brumat, Marco, Gasparini, Paolo, Toniolo, Daniela, Cocca, Massimiliano, Robino, Antonietta, Yazar, Seyhan, Hewitt, Alex W., Chen, Yan, Zeng, Changqing, Uitterlinden, Andre G., Ikram, M. Arfan, Hamer, Merel A., Van Duijn, Cornelia M., Nijsten, Tamar, MacKey, David A., Falchi, Mario, Boomsma, Dorret I., Martin, Nicholas G., Hinds, David A., Kayser, Manfred, and Spector, Timothy D.

Abstract

Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but 13 are novel. Collectively, single-nucleotide polymorphisms associated with hair color within these loci explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study populations. These results confirm the polygenic nature of complex phenotypes and improve our understanding of melanin pigment metabolism in humans.

Published
2018
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38. Genetic Susceptibility to Clozapine-Induced Agranulocytosis/Neutropenia Across Ethnicities: Results From a New Cohort of Turkish and Other Caucasian Participants, and Meta-Analysis.

Author

Okhuijsen-Pfeifer, Cynthia, Ayhan, Yavuz, Lin, Bochao D., van Eijk, Kristel R., Bekema, Erwin, Kool, Lindy J. G. B., Bogers, Jan P. A. M., Muderrisoglu, Ahmet, Babaoglu, Melih O., Van Assche, Evelien, Medic, Jelena, Veerman, Selene, Cohen, Dan, van Beek, Hanneke, de Jonge, Annemieke A. M., Beld, Edwin, Yağcıoğlu, A. Elif Anıl, and Luykx, Jurjen J.

Subjects
CLOZAPINE, ANTIPSYCHOTIC agents, NEUTROPENIA, AGRANULOCYTOSIS, PHARMACOGENOMICS, INDIVIDUALIZED medicine
Abstract

Clozapine (CLZ) is considered the most effective antipsychotic, but its use is associated with neutropenia (CIN) and agranulocytosis (CIA). Although the exact etiology of these hazardous side effects is unknown, 4 genetic polymorphisms have been implicated by genomewide association studies (GWAS), mostly performed in North-Western Europeans. These polymorphisms are rs113332494 (HLA-DQB1), rs41549217 (HLA-B), and rs1546308/rs149104283 (SLCO1B3/7), several of which were not directly genotyped but imputed. To test whether these 4 single-nucleotide polymorphisms (SNPs) are associated with CIN/CIA in a Turkish population and in a more extensive group of Caucasians, we directly genotyped these polymorphisms using Taqman and Sanger sequencing and performed logistic regression. We divided our participants (234 CLZ-using participants of whom 31 CIN/CIA cases) into (1) North-Western European, (2) Turkish, (3) Caucasian (=1 + 2); and (4) a total group (Caucasian + other ethnicities). Rs113332494 (HLA-DQB1) was significantly associated with CIN/CIA in the total group (P = 3.5 x 10-8), in the Caucasian group (P = 9.3 x 10-6) and in the Turkish group (P = 2.8 x 10-5). Rs41549217 (HLA-B) was nominally significant in the Caucasian group (P = .018). In meta-analysis of our results and the previously reported genome-wide results, 3 SNPs were significantly associated with CIN/CIA in participants with Caucasian ancestry: rs113332494 (P = 2.05 x 10-8), rs41549217 (P = 7.19 x 10-9), and rs149104283 (P = 5.54 x 10-9), with the result for rs1546308 (SCLO1B3/SCLO1B7) being significantly heterogeneous across studies. Our results hint at ethnicity-dependent and clinically relevant effects of genetic polymorphisms on the risk to develop CIN/CIA. Pharmacogenetic testing can complement clinical decision making and thus empower appropriate CLZ prescribing, but ancestry should be taken into account when performing such testing for CLZ. [ABSTRACT FROM AUTHOR]

Published
2020
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39. Heritability and GWAS Studies for Monocyte-Lymphocyte Ratio

Author

Lin, Bochao D, Willemsen, Gonneke, Fedko, Iryna O, Jansen, Rick, Penninx, B.W.J.H., de Geus, E, Kluft, C., Hottenga, J.J., Boomsma, Dorret I, Lin, Bochao D, Willemsen, Gonneke, Fedko, Iryna O, Jansen, Rick, Penninx, B.W.J.H., de Geus, E, Kluft, C., Hottenga, J.J., and Boomsma, Dorret I

Abstract

The monocyte-lymphocyte ratio (MLR) is a useful biomarker for disease development, but little is known about the extent to which genetic and environmental factors influence MLR variation. Here, we study the genetic architecture of MLR and determine the influence of demographic and lifestyle factors on MLR in data from a Dutch non-patient twin-family population. Data were obtained in 9,501 individuals from the Netherlands Twin Register. We used regression analyses to determine the effects of age, sex, smoking, and body mass index (BMI) on MLR and its subcomponents. Data on twins, siblings and parents (N = 7,513) were analyzed by genetic structural equation modeling to establish heritability and genome wide single nucleotide polymorphism (SNP) data from a genotyped subsample (N = 5,892) and used to estimate heritability explained by SNPs. SNP and phenotype data were also analyzed in a genome-wide association study to identify the genes involved in MLR. Linkage disequilibrium (LD) score regression and expression quantitative trait loci (eQTL) analyses were performed to further explore the genetic findings. Results showed that age, sex, and age × sex interaction effects were present for MLR and its subcomponents. Variation in MLR was not related to BMI, but smoking was positively associated with MLR. Heritability was estimated at 40% for MLR, 58% for monocyte, and 58% for lymphocyte count. The Genome-wide association study (GWAS) identified a locus on ITGA4 that was associated with MLR and only marginally significantly associated with monocyte count. For monocyte count, additional genetic variants were identified on ITPR3, LPAP1, and IRF8. For lymphocyte count, GWAS provided no significant findings. Taking all measured SNPs together, their effects accounted for 13% of the heritability of MLR, while all known and identified genetic loci explained 1.3% of variation in MLR. eQTL analyses showed that these genetic variants were unlikely to be eQTLs. In conclusion, variat

Published
2017
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42. Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability

Author

Seyhan Yazar, M. Arfan Ikram, Gonneke Willemsen, Maria Pina Concas, Manfred Kayser, Tim D. Spector, David M. Evans, Nicholas G. Martin, David L. Duffy, Changqing Zeng, Bochao D. Lin, Daniela Toniolo, Pirro G. Hysi, Gibran Hemani, Jouke-Jan Hottenga, Paolo Gasparini, Gu Zhu, Sarah E. Medland, Cornelia M. van Duijn, Mario Falchi, Marco Brumat, Nicholas A. Furlotte, Alessia Visconti, André G. Uitterlinden, Cinzia Sala, George McMahon, David A. Hinds, Dorret I. Boomsma, Ilaria Gandin, Ana M. Valdes, Dragana Vuckovic, Giorgia Girotto, Veronique Bataille, Massimiliano Cocca, David A. Mackey, Susan M. Ring, Fan Liu, Tamar Nijsten, Scott D. Gordon, Yan Chen, George Davey Smith, Merel A. Hamer, Antonietta Robino, Alex W. Hewitt, Genetic Identification, Erasmus MC other, Epidemiology, Internal Medicine, Dermatology, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Methodology, Hysi, Pirro G., Valdes, A. M., Liu, Fan, Furlotte, Nicholas A., Evans, David M., Bataille, Veronique, Visconti, Alessia, Hemani, Gibran, Mcmahon, George, Ring, Susan M., Smith, George Davey, Duffy, David L., Zhu, Gu, Gordon, Scott D., Medland, Sarah E., Lin, Bochao D., Willemsen, Gonneke, Jan Hottenga, Jouke, Vuckovic, Dragana, Girotto, Giorgia, Gandin, Ilaria, Sala, Cinzia, Concas, Maria Pina, Brumat, Marco, Gasparini, Paolo, Toniolo, Daniela, Cocca, Massimiliano, Robino, Antonietta, Yazar, Seyhan, Hewitt, Alex W., Chen, Yan, Zeng, Changqing, Uitterlinden, Andre G., Ikram, M. Arfan, Hamer, Merel A., van Duijn, Cornelia M., Nijsten, Tamar, Mackey, David A., Falchi, Mario, Boomsma, Dorret I., Martin, Nicholas G., Hinds, David A., Kayser, Manfred, and Spector, Timothy D.

Subjects
0301 basic medicine, Male, Netherlands Twin Register (NTR), Multifactorial Inheritance, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, White People, 03 medical and health sciences, 0302 clinical medicine, Black hair, Genetic variation, Genotype, Genetics, Eye color, otorhinolaryngologic diseases, Journal Article, Humans, Hair Color, Aged, Chromosomes, Human, X, Autosome, integumentary system, Heritability, Middle Aged, 030104 developmental biology, Phenotype, Evolutionary biology, Genetic Loci, Female, sense organs, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but 13 are novel. Collectively, single-nucleotide polymorphisms associated with hair color within these loci explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study populations. These results confirm the polygenic nature of complex phenotypes and improve our understanding of melanin pigment metabolism in humans.

Published
2018

43. Associations Between Genetic Risk, Physical Activities, and Distressing Psychotic-like Experiences.

Author

Ku BS, Yuan Q, Arias-Magnasco A, Lin BD, Walker EF, Druss BG, Ren J, van Os J, and Guloksuz S

Abstract

Background and Hypothesis: Persistent distressing psychotic-like experiences (PLE) are associated with impaired functioning and future psychopathology. Prior research suggests that physical activities may be protective against psychopathology. However, it is unclear whether physical activities may interact with genetics in the development of psychosis., Study Design: This study included 4679 participants of European ancestry from the Adolescent Brain Cognitive Development Study. Persistent distressing PLE was derived from the Prodromal-Questionnaire-Brief Child Version using four years of data. Generalized linear mixed models tested the association between polygenic risk score for schizophrenia (PRS-SCZ), physical activities, and PLE. The models adjusted for age, sex, parental education, income-to-needs ratio, family history of psychosis, body mass index, puberty status, principal components for PRS-SCZ, study site, and family., Study Results: PRS-SCZ was associated with a greater risk for persistent distressing PLE (adjusted relative risk ratio (RRR) = 1.14, 95% CI [1.04, 1.24], P = .003). Physical activity was associated with less risk for persistent distressing PLE (adjusted RRR = 0.87, 95% CI [0.79, 0.96], P = .008). Moreover, physical activities moderated the association between PRS-SCZ and persistent distressing PLE (adjusted RRR = 0.89, 95% CI [0.81, 0.98], P = .015), such that the association was weaker as participants had greater participation in physical activities., Conclusions: These findings demonstrate that the interaction between genetic liability and physical activities is associated with trajectories of distressing PLE. Further research is needed to understand the mechanisms of physical activities and genetic liability for schizophrenia in the development of psychosis., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Published
2024
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44. Examining the association between exposome score for schizophrenia and functioning in schizophrenia, siblings, and healthy controls: Results from the EUGEI study.

Author

Erzin G, Pries LK, van Os J, Fusar-Poli L, Delespaul P, Kenis G, Luykx JJ, Lin BD, Richards AL, Akdede B, Binbay T, Altınyazar V, Yalınçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran EŞ, Kaymak SU, Mihaljevic MM, Andric-Petrovic S, Mirjanic T, Bernardo M, Mezquida G, Amoretti S, Bobes J, Saiz PA, García-Portilla MP, Sanjuan J, Aguilar EJ, Santos JL, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric NP, Atbaşoğlu C, Ucok A, Alptekin K, Saka MC, Arango C, O'Donovan MC, Rutten BPF, and Guloksuz S

Subjects
Cross-Sectional Studies, Humans, Siblings, Exposome, Psychotic Disorders, Schizophrenia genetics
Abstract

Background: A cumulative environmental exposure score for schizophrenia (exposome score for schizophrenia [ES-SCZ]) may provide potential utility for risk stratification and outcome prediction. Here, we investigated whether ES-SCZ was associated with functioning in patients with schizophrenia spectrum disorder, unaffected siblings, and healthy controls., Methods: This cross-sectional sample consisted of 1,261 patients, 1,282 unaffected siblings, and 1,525 healthy controls. The Global Assessment of Functioning (GAF) scale was used to assess functioning. ES-SCZ was calculated based on our previously validated method. The association between ES-SCZ and the GAF dimensions (symptom and disability) was analyzed by applying regression models in each group (patients, siblings, and controls). Additional models included polygenic risk score for schizophrenia (PRS-SCZ) as a covariate., Results: ES-SCZ was associated with the GAF dimensions in patients (symptom: B = -1.53, p-value = 0.001; disability: B = -1.44, p-value = 0.001), siblings (symptom: B = -3.07, p-value < 0.001; disability: B = -2.52, p-value < 0.001), and healthy controls (symptom: B = -1.50, p-value < 0.001; disability: B = -1.31, p-value < 0.001). The results remained the same after adjusting for PRS-SCZ. The degree of associations of ES-SCZ with both symptom and disability dimensions were higher in unaffected siblings than in patients and controls. By analyzing an independent dataset (the Genetic Risk and Outcome of Psychosis study), we replicated the results observed in the patient group., Conclusions: Our findings suggest that ES-SCZ shows promise for enhancing risk prediction and stratification in research practice. From a clinical perspective, ES-SCZ may aid in efforts of clinical characterization, operationalizing transdiagnostic clinical staging models, and personalizing clinical management.

Published
2021
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45. Estimating Exposome Score for Schizophrenia Using Predictive Modeling Approach in Two Independent Samples: The Results From the EUGEI Study.

Author

Pries LK, Lage-Castellanos A, Delespaul P, Kenis G, Luykx JJ, Lin BD, Richards AL, Akdede B, Binbay T, Altinyazar V, Yalinçetin B, Gümüş-Akay G, Cihan B, Soygür H, Ulaş H, Cankurtaran EŞ, Kaymak SU, Mihaljevic MM, Petrovic SA, Mirjanic T, Bernardo M, Cabrera B, Bobes J, Saiz PA, García-Portilla MP, Sanjuan J, Aguilar EJ, Santos JL, Jiménez-López E, Arrojo M, Carracedo A, López G, González-Peñas J, Parellada M, Maric NP, Atbaşoğlu C, Ucok A, Alptekin K, Saka MC, Arango C, O'Donovan M, Rutten BPF, van Os J, and Guloksuz S

Subjects
Adult, Adverse Childhood Experiences statistics & numerical data, Area Under Curve, Bayes Theorem, Case-Control Studies, Child, Child Abuse, Sexual statistics & numerical data, Female, Humans, Logistic Models, Machine Learning, Male, Models, Statistical, Odds Ratio, ROC Curve, Seasons, Young Adult, Bullying statistics & numerical data, Child Abuse statistics & numerical data, Exposome, Hearing Loss epidemiology, Marijuana Use epidemiology, Schizophrenia epidemiology, Siblings
Abstract

Exposures constitute a dense network of the environment: exposome. Here, we argue for embracing the exposome paradigm to investigate the sum of nongenetic "risk" and show how predictive modeling approaches can be used to construct an exposome score (ES; an aggregated score of exposures) for schizophrenia. The training dataset consisted of patients with schizophrenia and controls, whereas the independent validation dataset consisted of patients, their unaffected siblings, and controls. Binary exposures were cannabis use, hearing impairment, winter birth, bullying, and emotional, physical, and sexual abuse along with physical and emotional neglect. We applied logistic regression (LR), Gaussian Naive Bayes (GNB), the least absolute shrinkage and selection operator (LASSO), and Ridge penalized classification models to the training dataset. ESs, the sum of weighted exposures based on coefficients from each model, were calculated in the validation dataset. In addition, we estimated ES based on meta-analyses and a simple sum score of exposures. Accuracy, sensitivity, specificity, area under the receiver operating characteristic, and Nagelkerke's R2 were compared. The ESMeta-analyses performed the worst, whereas the sum score and the ESGNB were worse than the ESLR that performed similar to the ESLASSO and ESRIDGE. The ESLR distinguished patients from controls (odds ratio [OR] = 1.94, P < .001), patients from siblings (OR = 1.58, P < .001), and siblings from controls (OR = 1.21, P = .001). An increase in ESLR was associated with a gradient increase of schizophrenia risk. In reference to the remaining fractions, the ESLR at top 30%, 20%, and 10% of the control distribution yielded ORs of 3.72, 3.74, and 4.77, respectively. Our findings demonstrate that predictive modeling approaches can be harnessed to evaluate the exposome., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Published
2019
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