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