Jaya L Padmanabhan1, Pranav Nanda2, Neeraj Tandon3, Suraj S Mothi4, Nicolas Bolo4, Steven McCarroll5, Brett A Clementz6, Elliot S Gershon7, Godfrey D Pearlson8, John A Sweeney9, Carol A Tamminga9, Matcheri S Keshavan10. 1. Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Behavioral Neurology and Neuropsychiatry, McLean Hospital, Belmont, MA, USA. 2. College of Physicians & Surgeons, Columbia University Medical Center, New York, NY, USA. 3. Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Baylor College of Medicine, Texas Medical Center, Houston, TX, USA. 4. Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA. 5. Department of Genetics, Harvard Medical School, Boston, MA, USA; Stanley Center for Psychiatric Research, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA. 6. Department of Psychology, BioImaging Research Center, University of Georgia, Athens, GA, USA; Department of Neuroscience, BioImaging Research Center, University of Georgia, Athens, GA, USA. 7. Department of Psychiatry and Behavioral Neuroscience, University of Chicago, IL, USA; Department of Human Genetics, University of Chicago, IL, USA. 8. Olin Neuropsychiatry Research Center, Institute of Living, Hartford, CT, USA; Departments of Psychiatry and Neurobiology, Yale University School of Medicine, New Haven, CT, USA. 9. Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, TX, USA. 10. Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA. Electronic address: mkeshava@bidmc.harvard.edu.
Abstract
BACKGROUND: An elevated prevalence of Type 2 diabetes (T2D) has been observed in people with psychotic disorders and their relatives compared to the general population. It is not known whether this population also has increased genetic risk for T2D. METHODS: Subjects included probands with schizophrenia, schizoaffective disorder, or psychotic bipolar I disorder, their first-degree relatives without psychotic disorders, and healthy controls, who participated in the Bipolar Schizophrenia Network for Intermediate Phenotypes study. We constructed sets of polygenic risk scores for T2D (PGRST2D) and schizophrenia (PGRSSCHIZ) using publicly available data from genome-wide association studies. We then explored the correlation of PGRST2D with psychiatric proband or relative status, and with self-reported diabetes. Caucasians and African-Americans were analyzed separately. We also evaluated correlations between PGRSSCHIZ and diabetes mellitus among Caucasian probands and their relatives. RESULTS: In Caucasians, PGRST2D was correlated with self-reported diabetes mellitus within probands, but was not correlated with proband or relative status in the whole sample. In African-Americans, a PGRST2D based on selected risk alleles for T2D in this population did not correlate with proband or relative status. PGRSSCHIZ was not correlated with self-reported diabetes within Caucasian probands. CONCLUSION: Differences in polygenic risk for T2D do not explain the increased prevalence of diabetes mellitus observed in psychosis probands and their relatives.
BACKGROUND: An elevated prevalence of Type 2 diabetes (T2D) has been observed in people with psychotic disorders and their relatives compared to the general population. It is not known whether this population also has increased genetic risk for T2D. METHODS: Subjects included probands with schizophrenia, schizoaffective disorder, or psychotic bipolar I disorder, their first-degree relatives without psychotic disorders, and healthy controls, who participated in the Bipolar Schizophrenia Network for Intermediate Phenotypes study. We constructed sets of polygenic risk scores for T2D (PGRST2D) and schizophrenia (PGRSSCHIZ) using publicly available data from genome-wide association studies. We then explored the correlation of PGRST2D with psychiatric proband or relative status, and with self-reported diabetes. Caucasians and African-Americans were analyzed separately. We also evaluated correlations between PGRSSCHIZ and diabetes mellitus among Caucasian probands and their relatives. RESULTS: In Caucasians, PGRST2D was correlated with self-reported diabetes mellitus within probands, but was not correlated with proband or relative status in the whole sample. In African-Americans, a PGRST2D based on selected risk alleles for T2D in this population did not correlate with proband or relative status. PGRSSCHIZ was not correlated with self-reported diabetes within Caucasian probands. CONCLUSION: Differences in polygenic risk for T2D do not explain the increased prevalence of diabetes mellitus observed in psychosis probands and their relatives.
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