Rikke Hilker1, Dorte Helenius2, Birgitte Fagerlund3, Axel Skytthe4, Kaare Christensen4, Thomas M Werge5, Merete Nordentoft6, Birte Glenthøj7. 1. CINS-Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; CNSR-Center for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark; Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark. Electronic address: rikke.hilker@regionh.dk. 2. Mental Health Centre Sct Hans, Mental Health Services, Capital Region of Denmark, Roskilde, Denmark; iPSYCH-Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. 3. CINS-Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; CNSR-Center for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark. 4. The Danish Twin Register, University of Southern Denmark, Odense, Denmark. 5. CINS-Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; Mental Health Centre Sct Hans, Mental Health Services, Capital Region of Denmark, Roskilde, Denmark; iPSYCH-Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. 6. CINS-Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; iPSYCH-Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark; Mental Health Centre Copenhagen, Mental Health Services, Capital Region of Denmark, Copenhagen, Denmark. 7. CINS-Lundbeck Foundation Center of Excellence for Clinical Intervention and Neuropsychiatric Schizophrenia Research, Glostrup, Denmark; CNSR-Center for Neuropsychiatric Schizophrenia Research, Mental Health Centre Glostrup, Mental Health Services, Capital Region of Denmark, Glostrup, Denmark; Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark.
Abstract
BACKGROUND: Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology. METHODS: Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951 and 2000 (N = 31,524 twin pairs). Twins were followed until June 1, 2011. Liability threshold models adjusting for censoring with inverse probability weighting were used to estimate probandwise concordance rates and heritability of the diagnoses of SZ and SZ spectrum disorders. RESULTS: The probandwise concordance rate of SZ is 33% in monozygotic twins and 7% in dizygotic twins. We estimated the heritability of SZ to be 79%. When expanding illness outcome to include SZ spectrum disorders, the heritability estimate was almost similar (73%). CONCLUSIONS: The key strength of this study is the application of a novel statistical method accounting for censoring in the follow-up period to a nationwide twin sample. The estimated 79% heritability of SZ is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader phenotype of SZ spectrum disorders. The low concordance rate of 33% in monozygotic twins demonstrates that illness vulnerability is not solely indicated by genetic factors.
BACKGROUND: Twin studies have provided evidence that both genetic and environmental factors contribute to schizophrenia (SZ) risk. Heritability estimates of SZ in twin samples have varied methodologically. This study provides updated heritability estimates based on nationwide twin data and an improved statistical methodology. METHODS: Combining two nationwide registers, the Danish Twin Register and the Danish Psychiatric Research Register, we identified a sample of twins born between 1951 and 2000 (N = 31,524 twin pairs). Twins were followed until June 1, 2011. Liability threshold models adjusting for censoring with inverse probability weighting were used to estimate probandwise concordance rates and heritability of the diagnoses of SZ and SZ spectrum disorders. RESULTS: The probandwise concordance rate of SZ is 33% in monozygotic twins and 7% in dizygotic twins. We estimated the heritability of SZ to be 79%. When expanding illness outcome to include SZ spectrum disorders, the heritability estimate was almost similar (73%). CONCLUSIONS: The key strength of this study is the application of a novel statistical method accounting for censoring in the follow-up period to a nationwide twin sample. The estimated 79% heritability of SZ is congruent with previous reports and indicates a substantial genetic risk. The high genetic risk also applies to a broader phenotype of SZ spectrum disorders. The low concordance rate of 33% in monozygotic twins demonstrates that illness vulnerability is not solely indicated by genetic factors.
Authors: Nirmal Vadgama; Alan Pittman; Michael Simpson; Niranjanan Nirmalananthan; Robin Murray; Takeo Yoshikawa; Peter De Rijk; Elliott Rees; George Kirov; Deborah Hughes; Tomas Fitzgerald; Mark Kristiansen; Kerra Pearce; Eliza Cerveira; Qihui Zhu; Chengsheng Zhang; Charles Lee; John Hardy; Jamal Nasir Journal: Eur J Hum Genet Date: 2019-03-18 Impact factor: 4.246
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Authors: Sinan Guloksuz; Lotta-Katrin Pries; Philippe Delespaul; Gunter Kenis; Jurjen J Luykx; Bochao D Lin; Alexander L Richards; Berna Akdede; Tolga Binbay; Vesile Altınyazar; Berna Yalınçetin; Güvem Gümüş-Akay; Burçin Cihan; Haldun Soygür; Halis Ulaş; EylemŞahin Cankurtaran; Semra Ulusoy Kaymak; Marina M Mihaljevic; Sanja Andric Petrovic; Tijana Mirjanic; Miguel Bernardo; Bibiana Cabrera; Julio Bobes; Pilar A Saiz; María Paz García-Portilla; Julio Sanjuan; Eduardo J Aguilar; José Luis Santos; Estela Jiménez-López; Manuel Arrojo; Angel Carracedo; Gonzalo López; Javier González-Peñas; Mara Parellada; Nadja P Maric; Cem Atbaşog Lu; Alp Ucok; Köksal Alptekin; Meram Can Saka; Celso Arango; Michael O'Donovan; Bart P F Rutten; Jim van Os Journal: World Psychiatry Date: 2019-06 Impact factor: 49.548