BACKGROUND: Epidemiological studies indicate that having any family member with schizophrenia increases the risk of schizophrenia in the probands. However, genome-wide association studies (GWAS) have accounted for little of this variation. The aim of this study was to use a population-based sample to explore the influence of single-nucleotide polymorphisms (SNPs) on the excess schizophrenia risk in offspring of parents with a psychotic, bipolar affective or other psychiatric disorder. METHOD: A nested case-control study with 739 cases with schizophrenia and 800 controls. Their parents and siblings. Information from national health registers and GWAS data from the national neonatal biobank. RESULTS: Offspring schizophrenia risk was elevated in those whose mother, father or siblings had been diagnosed with schizophrenia or related psychosis, bipolar affective disorder or any other psychiatric disorder. The rate ratio was 9.31 (3.85; 22.44) in offspring whose 1st degree relative was diagnosed with schizophrenia. This rate ranged between 8.31 and 11.34 when adjusted for each SNP individually and shrank to 8.23 (3.13; 21.64) when adjusted for 25% of the SNP-variation in candidate genes. The percentage of the excess risk associated with a family history of schizophrenia mediated through genome-wide SNP-variation ranged between -6.1%(-17.0%;2.6%) and 4.1%(-3.9%;15.2%). Analogous results were seen for each parent and for histories of bipolar affective and other psychiatric diagnoses. CONCLUSIONS: The excess risk of schizophrenia in offspring of parents who have a psychotic, bipolar affective or other psychiatric disorder is not currently explained by the SNP variation included in this study in accordance with findings from published genetic studies.
BACKGROUND: Epidemiological studies indicate that having any family member with schizophrenia increases the risk of schizophrenia in the probands. However, genome-wide association studies (GWAS) have accounted for little of this variation. The aim of this study was to use a population-based sample to explore the influence of single-nucleotide polymorphisms (SNPs) on the excess schizophrenia risk in offspring of parents with a psychotic, bipolar affective or other psychiatric disorder. METHOD: A nested case-control study with 739 cases with schizophrenia and 800 controls. Their parents and siblings. Information from national health registers and GWAS data from the national neonatal biobank. RESULTS: Offspring schizophrenia risk was elevated in those whose mother, father or siblings had been diagnosed with schizophrenia or related psychosis, bipolar affective disorder or any other psychiatric disorder. The rate ratio was 9.31 (3.85; 22.44) in offspring whose 1st degree relative was diagnosed with schizophrenia. This rate ranged between 8.31 and 11.34 when adjusted for each SNP individually and shrank to 8.23 (3.13; 21.64) when adjusted for 25% of the SNP-variation in candidate genes. The percentage of the excess risk associated with a family history of schizophrenia mediated through genome-wide SNP-variation ranged between -6.1%(-17.0%;2.6%) and 4.1%(-3.9%;15.2%). Analogous results were seen for each parent and for histories of bipolar affective and other psychiatric diagnoses. CONCLUSIONS: The excess risk of schizophrenia in offspring of parents who have a psychotic, bipolar affective or other psychiatric disorder is not currently explained by the SNP variation included in this study in accordance with findings from published genetic studies.
Authors: S M Meier; E Agerbo; R Maier; C B Pedersen; M Lang; J Grove; M V Hollegaard; D Demontis; B B Trabjerg; C Hjorthøj; S Ripke; F Degenhardt; M M Nöthen; D Rujescu; W Maier; T Werge; O Mors; D M Hougaard; A D Børglum; N R Wray; M Rietschel; M Nordentoft; P B Mortensen; M Mattheisen Journal: Mol Psychiatry Date: 2015-09-01 Impact factor: 15.992
Authors: Pia Jeppesen; Janne Tidselbak Larsen; Lars Clemmensen; Anja Munkholm; Martin Kristian Rimvall; Charlotte Ulrikka Rask; Jim van Os; Liselotte Petersen; Anne Mette Skovgaard Journal: Schizophr Bull Date: 2014-12-01 Impact factor: 9.306
Authors: D Paksarian; B B Trabjerg; K R Merikangas; O Mors; A D Børglum; D M Hougaard; J J McGrath; C B Pedersen; P B Mortensen; E Agerbo Journal: Psychol Med Date: 2017-06-29 Impact factor: 7.723
Authors: Anna Wiste; Elise B Robinson; Yuri Milaneschi; Sandra Meier; Stephan Ripke; Caitlin C Clements; Garrett M Fitzmaurice; Marcella Rietschel; Brenda W Penninx; Jordan W Smoller; Roy H Perlis Journal: Bipolar Disord Date: 2014-04-12 Impact factor: 6.744
Authors: Annette Erlangsen; Vivek Appadurai; Yunpeng Wang; Gustavo Turecki; Ole Mors; Thomas Werge; Preben B Mortensen; Anna Starnawska; Anders D Børglum; Andrew Schork; Ron Nudel; Marie Bækvad-Hansen; Jonas Bybjerg-Grauholm; David M Hougaard; Wesley K Thompson; Merete Nordentoft; Esben Agerbo Journal: Mol Psychiatry Date: 2018-08-16 Impact factor: 15.992
Authors: Antonella Trotta; Marta Di Forti; Conrad Iyegbe; Priscilla Green; Paola Dazzan; Valeria Mondelli; Craig Morgan; Robin M Murray; Helen L Fisher Journal: BJPsych Open Date: 2015-06-23
Authors: C B Pedersen; J Bybjerg-Grauholm; M G Pedersen; J Grove; E Agerbo; M Bækvad-Hansen; J B Poulsen; C S Hansen; J J McGrath; T D Als; J I Goldstein; B M Neale; M J Daly; D M Hougaard; O Mors; M Nordentoft; A D Børglum; T Werge; P B Mortensen Journal: Mol Psychiatry Date: 2017-09-19 Impact factor: 15.992