title: Familial Aggregation and Heritability of Schizophrenia and Co-aggregation of Psychiatric Illnesses in Affected Families.
abstract: Strong familial aggregation of schizophrenia has been reported but there is uncertainty concerning the degree of genetic contribution to the phenotypic variance of the disease. This study aimed to examine the familial aggregation and heritability of schizophrenia, and the relative risks (RRs) of other psychiatric diseases, in relatives of people with schizophrenia using the Taiwan National Health Insurance Database. The study population included individuals with affected first-degree or second-degree relatives identified from all beneficiaries (n = 23 422 955) registered in 2013. Diagnoses of schizophrenia made by psychiatrists were ascertained between January 1, 1996 and December 31, 2013. Having an affected co-twin, first-degree relative, second-degree relative, or spouse was associated with an adjusted RR (95% CI) of 37.86 (30.55-46.92), 6.30 (6.09-6.53), 2.44 (1.91-3.12), and 1.88 (1.64-2.15), respectively. Compared with the general population, individuals with one affected first-degree relative had a RR (95% CI) of 6.00 (5.79-6.22) and those with 2 or more had a RR (95% CI) of 14.66 (13.00-16.53) for schizophrenia. The accountability for the phenotypic variance of schizophrenia was 47.3% for genetic factors, 15.5% for shared environmental factors, and 37.2% for non-shared environmental factors. The RR (95% CI) in individuals with a first-degree relative with schizophrenia was 3.49 (3.34-3.64) for mood disorders and 3.91 (3.35-4.57) for delusional disorders. A family history of schizophrenia is therefore associated with a higher risk of developing schizophrenia, mood disorders, and delusional disorders. Heritability and environmental factors each account for half of the phenotypic variance of schizophrenia.
authors.affiliation: Division of Clinical Neuroscience, School of Medicine, University of Nottingham, Nottingham, UK.|Division of Paediatric Neurology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: I-Jun
authors.initials: IJ
authors.lastname: Chou
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.|Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Chang-Fu
authors.initials: CF
authors.lastname: Kuo
authors.affiliation: Department of Child Psychiatry, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|School of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Yu-Shu
authors.initials: YS
authors.lastname: Huang
authors.affiliation: Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Grainge
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Ana M
authors.initials: AM
authors.lastname: Valdes
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Department of Public Health, College of Medicine and Biostatistics Core Laboratory, Molecular Medicine Research Centre, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Lai-Chu
authors.initials: LC
authors.lastname: See
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|School of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Kuang-Hui
authors.initials: KH
authors.lastname: Yu
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|School of Medicine, Chang Gung University, Taoyuan, Taiwan.
authors.forename: Shue-Fen
authors.initials: SF
authors.lastname: Luo
authors.affiliation: Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Lu-Shuang
authors.initials: LS
authors.lastname: Huang
authors.affiliation: Kennedy Institute of Rheumatology, University of Oxford, Oxford, UK.|Division of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Keelung, Taiwan.
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Tseng
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Weiya
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Division of Rheumatology, Orthopaedics and Dermatology, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Michael
authors.initials: M
authors.lastname: Doherty
mesh_terms: D000328:Adult; D005190:Family; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D019964:Mood Disorders / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D012042:Registries / Q000706:statistics & numerical data*; D012306:Risk; D012559:Schizophrenia / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics*; D012563:Schizophrenia, Paranoid / Q000453:epidemiology / Q000209:etiology / Q000235:genetics; D013624:Taiwan / Q000453:epidemiology; D055815:Young Adult
keywords: delusional disorders; familial aggregation; heritability; mood disorders; schizophrenia