1. Genetic risk scores and family history as predictors of schizophrenia in Nordic registers
- Author
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Srdjan Djurovic, Yi Lu, Andres Metspalu, Patrick F. Sullivan, Thomas Werge, Jennie G. Pouget, Christina M. Hultman, Ole A. Andreassen, Tõnu Esko, and Lili Milani
- Subjects
Adult ,Estonia ,Male ,0301 basic medicine ,medicine.medical_specialty ,Multivariate analysis ,Genome-wide association study ,Scandinavian and Nordic Countries ,Risk Assessment ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,mental disorders ,medicine ,Humans ,Genetic Predisposition to Disease ,Registries ,Bipolar disorder ,Risk factor ,Family history ,Medical History Taking ,Psychiatry ,Applied Psychology ,business.industry ,fungi ,Middle Aged ,medicine.disease ,Psychiatry and Mental health ,Logistic Models ,030104 developmental biology ,Schizophrenia ,Case-Control Studies ,Multivariate Analysis ,Autism ,Female ,business ,Risk assessment ,030217 neurology & neurosurgery ,Genome-Wide Association Study ,Clinical psychology - Abstract
BackgroundFamily history is a long-standing and readily obtainable risk factor for schizophrenia (SCZ). Low-cost genotyping technologies have enabled large genetic studies of SCZ, and the results suggest the utility of genetic risk scores (GRS, direct assessments of inherited common variant risk). Few studies have evaluated family history and GRS simultaneously to ask whether one can explain away the other.MethodsWe studied 5959 SCZ cases and 8717 controls from four Nordic countries. All subjects had family history data from national registers and genome-wide genotypes that were processed through the quality control procedures used by the Psychiatric Genomics Consortium. Using external training data, GRS were estimated for SCZ, bipolar disorder (BIP), major depression, autism, educational attainment, and body mass index. Multivariable modeling was used to estimate effect sizes.ResultsUsing harmonized genomic and national register data from Denmark, Estonia, Norway, and Sweden, we confirmed that family history of SCZ and GRS for SCZ and BIP were risk factors for SCZ. In a joint model, the effects of GRS for SCZ and BIP were essentially unchanged, and the effect of family history was attenuated but remained significant. The predictive capacity of a model including GRS and family history neared the minimum for clinical utility.ConclusionsCombining national register data with measured genetic risk factors represents an important investigative approach for psychotic disorders. Our findings suggest the potential clinical utility of combining GRS and family history for early prediction and diagnostic improvements.
- Published
- 2017