Characterisation of age and polarity at onset in bipolar disorder
Jazyk angličtina Země Velká Británie, Anglie Médium print
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural
Grantová podpora
R01 MH104964
NIMH NIH HHS - United States
G1000708
Medical Research Council - United Kingdom
R01 MH124873
NIMH NIH HHS - United States
K99 MH116115
NIMH NIH HHS - United States
R01 MH123451
NIMH NIH HHS - United States
Wellcome Trust - United Kingdom
R01 MH113078
NIMH NIH HHS - United States
R00 MH116115
NIMH NIH HHS - United States
Odkazy
PubMed
35048876
PubMed Central
PMC8636611
DOI
10.1192/bjp.2021.102
PII: S0007125021001021
Knihovny.cz E-zdroje
- Klíčová slova
- Bipolar disorder, GWAS, age at onset, polarity at onset, polygenic score,
- MeSH
- bipolární porucha * diagnóza epidemiologie genetika MeSH
- celogenomová asociační studie MeSH
- depresivní porucha unipolární * genetika MeSH
- lidé MeSH
- multifaktoriální dědičnost MeSH
- poruchy autistického spektra * MeSH
- věk při počátku nemoci MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Research Support, N.I.H., Extramural MeSH
BACKGROUND: Studying phenotypic and genetic characteristics of age at onset (AAO) and polarity at onset (PAO) in bipolar disorder can provide new insights into disease pathology and facilitate the development of screening tools. AIMS: To examine the genetic architecture of AAO and PAO and their association with bipolar disorder disease characteristics. METHOD: Genome-wide association studies (GWASs) and polygenic score (PGS) analyses of AAO (n = 12 977) and PAO (n = 6773) were conducted in patients with bipolar disorder from 34 cohorts and a replication sample (n = 2237). The association of onset with disease characteristics was investigated in two of these cohorts. RESULTS: Earlier AAO was associated with a higher probability of psychotic symptoms, suicidality, lower educational attainment, not living together and fewer episodes. Depressive onset correlated with suicidality and manic onset correlated with delusions and manic episodes. Systematic differences in AAO between cohorts and continents of origin were observed. This was also reflected in single-nucleotide variant-based heritability estimates, with higher heritabilities for stricter onset definitions. Increased PGS for autism spectrum disorder (β = -0.34 years, s.e. = 0.08), major depression (β = -0.34 years, s.e. = 0.08), schizophrenia (β = -0.39 years, s.e. = 0.08), and educational attainment (β = -0.31 years, s.e. = 0.08) were associated with an earlier AAO. The AAO GWAS identified one significant locus, but this finding did not replicate. Neither GWAS nor PGS analyses yielded significant associations with PAO. CONCLUSIONS: AAO and PAO are associated with indicators of bipolar disorder severity. Individuals with an earlier onset show an increased polygenic liability for a broad spectrum of psychiatric traits. Systematic differences in AAO across cohorts, continents and phenotype definitions introduce significant heterogeneity, affecting analyses.
Alexandru Obregia Clinical Psychiatric Hospital Bucharest Romania
Dalla Lana School of Public Health Biostatistics Division University of Toronto Canada
Department of Biochemistry and Molecular Biology Indiana University School of Medicine USA
Department of Clinical Sciences Medical Faculty Umeå University Sweden
Department of Medicine Surgery and Dentistry 'Scuola Medica Salernitana' University of Salerno Italy
Department of Psychiatric Genetics Poznan University of Medical Sciences Poland
Department of Psychiatry and Behavioral Sciences Emory University USA
Department of Psychiatry and Behavioral Sciences Howard University Hospital USA
Department of Psychiatry and Behavioral Sciences Johns Hopkins University USA
Department of Psychiatry and Psychology Mayo Clinic USA
Department of Psychiatry and Psychotherapeutic Medicine Medical University Graz Austria
Department of Psychiatry and Psychotherapy Charite Universitätsmedizin Germany
Department of Psychiatry and Psychotherapy Philipps University Marburg Germany
Department of Psychiatry and Psychotherapy University Hospital Munich Germany
Department of Psychiatry and Psychotherapy University Medical Center Göttingen Germany
Department of Psychiatry and Trinity Translational Medicine Institute Trinity College Dublin Ireland
Department of Psychiatry Dalhousie University Canada
Department of Psychiatry Geneva University Hospitals Switzerland
Department of Psychiatry Icahn School of Medicine at Mount Sinai USA
Department of Psychiatry McGill University Canada
Department of Psychiatry McGill University Canada; and Douglas Institute McGill University Canada
Department of Psychiatry Rush Medical College USA
Department of Psychiatry Stony Brook University USA
Department of Psychiatry University of California San Diego USA
Department of Psychiatry University of Campania 'Luigi Vanvitelli' Italy
Department of Psychiatry University of Michigan USA
Department of Psychiatry University of Perugia Italy
Department of Translational Research Max Planck Institute of Psychiatry Germany
Discipline of Psychiatry University of Adelaide Australia; and Bazil Hetzel Institute Australia
Division of Psychiatric Genomics Mount Sinai School of Medicine USA
Division of Psychiatry University College London UK
Division of Psychiatry University of Edinburgh UK
Hospital Clinic University of Barcelona IDIBAPS CIBERSAM Spain
Human Genetics Branch Intramural Research Program National Institute of Mental Health USA
Institute for Genomic Health SUNY Downstate Medical Center College of Medicine USA
Institute for Translational Psychiatry Westfälische Wilhelms Universität Münster Germany
Institute of Psychiatric Phenomics and Genomics Spain
Institute of Psychiatric Phenomics and Genomics University Hospital LMU Munich Germany
Max Planck Institute of Psychiatry Germany
Mental Health Department University Regional Hospital Biomedicine Institute Spain
Montreal Neurological Institute Canada and Department of Neurology McGill University Canada
Mood Disorders Centre of Ottawa Canada; and Department of Psychiatry University of Toronto Canada
National Institute of Mental Health Czech Republic
Neuroscience Janssen Research and Development USA
NORMENT Centre Division of Mental Health and Addiction Oslo University Hosptial Norway
NORMENT Division of Mental Health and Addiction Oslo University Hospital Norway
Nova Scotia Health Authority Canada
Psychiatric Clinic Alexander University Hospital Bulgaria
Psychiatry and the Behavioral Sciences University of Southern California USA
Psychiatry Indiana University School of Medicine USA
Psychiatry UMC Utrecht Brain Center the Netherlands
Psychiatry University of California San Francisco USA
Psychiatry University of Pennsylvania USA
Psychological Medicine University of Worcester UK
Research Institute Lindner Center of HOPE USA
School of Psychiatry University of New South Wales Australia
Translational Genomics USC USA
Unit of Clinical Pharmacology University Hospital Agency of Cagliari Italy
Universite Paris Est Creteil France; and INSERM U 955 Neuropsychiatrie Translationnelle France