The vastly reduced life expectancy in schizophrenia is primarily due to medical comorbidities, yet these are often overlooked in a research context. Numerous psychiatric and somatic diagnoses have increased rates in schizophrenia, and the majority of schizophrenia patients have comorbid conditions. Since lifestyle factors and medication side-effects likely contribute to many of these increased medical problems, it has been difficult to resolve the extent to which shared biological underpinnings contribute to comorbid conditions.
The aims for this proposal will be accomplished using data from the Genomic Aggregation Project in Sweden (GAPS) with >200k genotyped subjects and comprehensive medical and demographic information from the Swedish National Registers. This wealth of information allows for additional clinical risk from schizophrenia-associated variants to be captured.
In Aim 1, carriers of previously identified schizophrenia risk variants without this diagnosis will be studied for increased risk of diagnoses across multiple psychiatric and somatic domains compared to non-carriers using logistic regression. Furthermore, comorbidities may offer clues to the pathophysiological mechanisms leading to different forms of schizophrenia. With this in mind, comorbid conditions will be leveraged to define schizophrenia subtypes in Aim 2 using the >5000 cases in the Swedish Schizophrenia Study within GAPS. Following cluster analysis using comorbidities, validity will be assessed by testing for group differences in genetic and clinical variation. These studies will yield new insights into the relationships between schizophrenia and other medical conditions, and identify subtypes of schizophrenia that will facilitate personalized medical care.
Comorbidities are a fundamental feature of schizophrenia and may arise due to shared biological foundations, deleterious lifestyle factors or combinations of these influences. This study explores the origins of these comorbidities by studying the extent to which genetic risk for schizophrenia in unaffected individuals impacts risk for other psychiatric or somatic diagnoses. Furthermore, in a population with schizophrenia, patterns of comorbidity will be leveraged to identify subtypes with etiological and clinical significance.
