Suchergebnisse

Anecdotal and biographical reports have long suggested that bipolar disorder is more common in people with exceptional cognitive or creative ability. Epidemiological evidence for such a link is sparse. We investigated the relationship between intelligence and subsequent risk of hospitalisation for bipolar disorder in a prospective cohort study of 1,049,607 Swedish men. Intelligence was measured on conscription for military service at a mean age of 18.3 years and data on psychiatric hospital admissions over a mean follow-up period of 22.6 years was obtained from national records. Risk of hospitalization with any form of bipolar disorder fell in a stepwise manner as intelligence increased (p for linear trend <0.0001). However, when we restricted analyses to men with no psychiatric comorbidity, there was a 'reversed-J' shaped association: men with the lowest intelligence had the greatest risk of being admitted with pure bipolar disorder, but risk was also elevated among men with the highest intelligence (p for quadratic trend = 0.03), primarily in those with the highest verbal (p for quadratic trend=0.009) or technical ability (p for quadratic trend <0.0001). At least in men, high intelligence may indeed be a risk factor for bipolar disorder, but only in the minority of cases who have the disorder in a pure form with no psychiatric comorbidity.

Copyright: © 2013 Tenesa et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Genotyping of the ABC1936, LBC1921, and LBC1936 cohorts and the analyses conducted here were supported by the UK's Biotechnology and Biological Sciences Research Council (BBSRC). Phenotype collection in the Lothian Birth Cohort 1921 was supported by the BBSRC, The Royal Society, and The Chief Scientist Office of the Scottish Government. Phenotype collection in the Lothian Birth Cohort 1936 was supported by Research Into Ageing (continues as part of Age UK's The Disconnected Mind project). Phenotype collection in the Aberdeen Birth Cohort 1936 was supported by the BBSRC, the Wellcome Trust, and the Alzheimer's Research Trust. SJR, AR and AT are funded by the BBSRC through the Roslin Institute's strategic programme grant and project grant BB/K000195/1. The Brain data was provided by the Division of Aging Biology and the Division of Geriatrics and Clinical Gerontology (NIA) through the NIH GWAS Data Repository (dbGaP Accession Number: phs000249.v1.p1) and funded as part of the Intramural Research Program, NIA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ; Peer reviewed ; Publisher PDF

ACKNOWLEDGEMENTS We are grateful to the families who took part in GS:SFHS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole GS team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z. The Chief Scientist Office of the Scottish Government and the Scottish Funding Council provided core support for Generation Scotland. GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office, number CZD/16/6. We acknowledge with gratitude the financial support received for this work from the Dr Mortimer and Theresa Sackler Foundation. PT, DJP, IJD, and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged. ; Peer reviewed ; Publisher PDF

Acknowledgements: The authors thank all LBC study participants and research team members who have contributed, and continue to contribute, to the ongoing LBC study. The LBC1936 is supported by Age UK (Disconnected Mind programme) and the Medical Research Council [MR/M01311/1]. The LBC1921 is supported by the Biotechnology and Biological Sciences Research Council [SR176], the Chief Scientist Office [CZB/4/505; ETM/55] and the Medical Research Council [R42550]. Methylation typing was supported by the Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland. This work was conducted in the Centre for Cognitive Ageing and Cognitive Epidemiology, which is supported by the Medical Research Council and Biotechnology and Biological Sciences Research Council [MR/K026992/1], and which supports Ian Deary. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" [(STRADL) 104036/Z/14/Z]) ; Peer reviewed ; Publisher PDF

This work was supported by a Alzheimer's Research UK Major Project grant (ARUK-PG2017B-10). Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team that includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, health-care assistants and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland, and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" [STRADL];104036/Z/14/Z). DNA methylation data collection was funded by the Wellcome Trust Strategic Award (10436/Z/14/Z). The research was conducted in the University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross-council Lifelong Health and Wellbeing Initiative (MR/K026992/1); funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. CCACE supports I.J.D. with some additional support from the Dementias Platform UK (MR/L015382/1). A.M.M. and H.C.W. have received support from the Sackler Institute. ; Peer reviewed ; Publisher PDF

We are grateful to the families who took part in GS:SFHS, general practitioners and the Scottish School of Primary Care for their help in recruitment, and the whole GS:SFHS team that includes academic researchers, clinic staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. The research reported here, and the genotyping of GS:SFHS samples was funded by the Wellcome Trust, (Wellcome Trust Strategic Award 'STratifying Resilience and Depression Longitudinally' (STRADL) Reference 104036/Z/14/Z) and by the Medical Research Council. SF acknowledges support from the National Institute of Mental Health, USA (R01MH113619; R01MH116147) and the consortium for Psychopathology and Allostatic load across the Life Span (PALS; https://www.pals-network.org) AMM acknowledges the financial support received from the Dr. Mortimer and Theresa Sackler Foundation. IJD and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Funding from the Biotechnology and Biological Sciences Research Council and Medical Research Council is gratefully acknowledged. ; Peer reviewed ; Publisher PDF

Variation in human cognitive ability is of consequence to a large number of health and social outcomes and is substantially heritable. Genetic linkage, genome-wide association, and copy number variant studies have investigated the contribution of genetic variation to individual differences in normal cognitive ability, but little research has considered the role of rare genetic variants. Exome sequencing studies have already met with success in discovering novel trait-gene associations for other complex traits. Here, we use exome sequencing to investigate the effects of rare variants on general cognitive ability. Unrelated Scottish individuals were selected for high scores on a general component of intelligence (g). The frequency of rare genetic variants (in n = 146) was compared with those from Scottish controls (total n = 486) who scored in the lower to middle range of the g distribution or on a proxy measure of g. Biological pathway analysis highlighted enrichment of the mitochondrial inner membrane component and apical part of cell gene ontology terms. Global burden analysis showed a greater total number of rare variants carried by high g cases versus controls, which is inconsistent with a mutation load hypothesis whereby mutations negatively affect g. The general finding of greater non-synonymous (vs. synonymous) variant effects is in line with evolutionary hypotheses for g. Given that this first sequencing study of high g was small, promising results were found, suggesting that the study of rare variants in larger samples would be worthwhile.

Generation Scotland has received core funding from the Chief Scientist Office of the Scottish Government Health DirectoratesCZD/16/6 and the Scottish Funding CouncilHR03006. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the UK's Medical Research Council. The Quantitative Trait Locus team at the Human Genetics Unit is funded by the Medical Research Council. REM, GD, DL, ML, DJP, PMV, and IJD undertook the work within The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (MR/K026992/1), part of the cross council Lifelong Health and Wellbeing Initiative. Funding from the BBSRC and MRC is gratefully acknowledged. REM is an Alzheimer's Research UK Fellow (ART-RF2010-2). ; Peer reviewed ; Publisher PDF

Acknowledgements: This work was supported by Alzheimer's Research UK Major Project Grant [ARUK–PG2017B–10]. Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006]. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants, and nurses. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" (STRADL) [104036/Z/14/Z]. DNA methylation data collection was funded by the Wellcome Trust Strategic Award [10436/Z/14/Z]. The research was conducted in The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology (CCACE), part of the cross–council Lifelong Health and Wellbeing Initiative [MR/K026992/1]; funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged. CCACE supports Ian Deary, with some additional support from Dementias Platform UK [MR/L015382/1]. HCW is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh. AMM and HCW have received support from the Sackler Institute ; Peer reviewed ; Publisher PDF

Generation Scotland received core funding from the Chief Scientist Office of the Scottish Government Health Directorate CZD/16/6 and the Scottish Funding Council HR03006. Genotyping of the GS:SFHS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award "STratifying Resilience and Depression Longitudinally" (STRADL) Reference 104036/Z/14/Z. YZ acknowledges support from China Scholarship Council. IJD is supported by the Centre for Cognitive Ageing and Cognitive Epidemiology which is funded by the Medical Research Council and the Biotechnology and Biological Sciences Research Council (MR/K026992/1). AMMcI and T-KC acknowledges support from the Dr Mortimer and Theresa Sackler Foundation. We are grateful to all the families who took part, the general practitioners and the Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists, healthcare assistants and nurses. Ethics approval for the study was given by the NHS Tayside committee on research ethics (reference 05/S1401/8) ; Peer reviewed ; Publisher PDF

Acknowledgements We are grateful to the families who took part in GS:SFHS, the GPs and Scottish School of Primary Care for their help in recruiting them, and the whole GS team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, IT staff, statisticians and research managers. Funded by Scottish Government Health Department, Chief Scientist Office. Grant Number: CZD/16/6 National Institutes of Health. Grant Numbers: N01-HG-65403, HHSN268200782096C, RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, P50 AA12870, MSTP T32GM07205, CTSA 8UL1TR000142 NIH Genes, Environment and Health Initiative [GEI]. Grant Numbers: U01 HG004422, U01HG004438 Gene Environment Association Studies (GENEVA). Grant Number: U01 HG004446 Collaborative Study on the Genetics of Alcoholism. Grant Number: U10 AA008401 Collaborative Genetic Study of Nicotine Dependence. Grant Number: P01 CA089392 Family Study of Cocaine Dependence. Grant Number: R01 DA013423 National Institute on Alcohol Abuse and Alcoholism National Institute on Drug Abuse Dr Mortimer and Theresa Sackler Foundation Biotechnology and Biological Sciences Research Council (BBSRC) Medical Research Council (MRC) ; Peer reviewed ; Publisher PDF

This work is supported by the Wellcome Trust through a Strategic Award, reference 104036/Z/14/Z. GS:SFHS was funded by a grant from the Scottish Government Health Department, Chief Scientist Office, number CZD/16/6. The authors acknowledge with gratitude the financial support received for this work from the Dr. Mortimer and Theresa Sackler Foundation. PAT, DJP and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). Funding from the Biotechnology and Biological Sciences Research Council (BBSRC) and Medical Research Council (MRC) is gratefully acknowledged by PN and CSH (BB/J004235/1). DJM is an NRS Fellow, funded by the CSO. ; Peer reviewed ; Publisher PDF

ACKNOWLEDGEMENTS We would like to thank all of the Generation Scotland participants for their contribution to this study. We also thank the research assistants, clinicians and technicians for their help in collecting the data. Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates [CZD/16/6] and the Scottish Funding Council [HR03006] and is currently supported by the Wellcome Trust [216767/Z/19/Z]. This study was also supported and funded by the Wellcome Trust Strategic Award 'Stratifying Resilience and Depression Longitudinally' (STRADL) (Reference 104036/Z/14/Z). We acknowledge the support of the British Heart Foundation (RE/18/5/34216). CG is supported by the Medical Research Council and the University of Edinburgh through the Precision Medicine Doctoral Training Programme. MCB is supported by a Guarantors of Brain Non-Clinical Post-Doctoral Fellowship. JMW is funded by the UK Dementia Research Institute which is funded by the UK Medical Research Council, Alzheimer's Research UK and Alzheimer's Society ; Peer reviewed ; Publisher PDF

This work was supported by the Wellcome Trust through a Strategic Award Reference No. 104036/Z/14/Z, the Dr. Mortimer and Theresa Sackler Foundation (T-KC and AMM), the Medical Research Council (MRC) to the Human Genetics Unit (PN and CSH), and the Biotechnology and Biological Sciences Research Council Grant No. BB/J004235/1 (PN and CSH). The Chief Scientist Office of the Scottish Government and the Scottish Funding Council provided core support for Generation Scotland (GS). GS: The Scottish Family Health Study (SFHS) was funded by a grant from the Scottish Government Health Department, Chief Scientist Office, No. CZD/16/6. This work was also supported by National Institutes of Health Grant No. UO1MH105630. We thank the families who took part in GS:SFHS, the general practitioners, and Scottish School of Primary Care for their help in recruiting them, and the whole GS team, which includes academic researchers, clinic staff, laboratory technicians, clerical workers, information technology staff, statisticians, and research managers. YZ thanks Mr. Ian White for the suggestion for analysis of polygenic score. AMF-P, LSH, BHS, LJH, SP, CH, and NRW report no biomedical financial interests or potential conflicts of interest. YZ received support from China Scholarship Council. PN and CSH received support from the MRC. T-KC and AMM received financial support for this work from the Dr. Mortimer and Theresa Sackler Foundation. PAT, IJD, DJP, and AMM are members of The University of Edinburgh Centre for Cognitive Ageing and Cognitive Epidemiology, part of the cross council Lifelong Health and Wellbeing Initiative (MR/K026992/1). DJM is an NRS (National Health Service Research Scotland) Fellow, funded by the Chief Scientist Office. AMM previously received grant support from Pfizer, Lilly, and Janssen; those studies are not connected to the present investigation. ; Peer reviewed ; Publisher PDF