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Abstract

Objective:

Individuals at high risk for schizophrenia may benefit from early intervention, but few validated risk predictors are available. Genetic profiling is one approach to risk stratification that has been extensively validated in research cohorts. The authors sought to test the utility of this approach in clinical settings and to evaluate the broader health consequences of high genetic risk for schizophrenia.

Methods:

The authors used electronic health records for 106,160 patients from four health care systems to evaluate the penetrance and pleiotropy of genetic risk for schizophrenia. Polygenic risk scores (PRSs) for schizophrenia were calculated from summary statistics and tested for association with 1,359 disease categories, including schizophrenia and psychosis, in phenome-wide association studies. Effects were combined through meta-analysis across sites.

Results:

PRSs were robustly associated with schizophrenia (odds ratio per standard deviation increase in PRS, 1.55; 95% CI=1.4, 1.7), and patients in the highest risk decile of the PRS distribution had up to 4.6-fold higher odds of schizophrenia compared with those in the bottom decile (95% CI=2.9, 7.3). PRSs were also positively associated with other phenotypes, including anxiety, mood, substance use, neurological, and personality disorders, as well as suicidal behavior, memory loss, and urinary syndromes; they were inversely related to obesity.

Conclusions:

The study demonstrates that an available measure of genetic risk for schizophrenia is robustly associated with schizophrenia in health care settings and has pleiotropic effects on related psychiatric disorders as well as other medical syndromes. The results provide an initial indication of the opportunities and limitations that may arise with the future application of PRS testing in health care systems.

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Supplementary Material

File (ajp_18091085_ds002_supplementarytables.xlsx)
File (ajp_18091085_ds003_supplementaryfigures.pdf)
File (appi.ajp.2019.18091085.ds001.pdf)

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 846 - 855
PubMed: 31416338

History

Received: 20 September 2018
Revision received: 20 March 2019
Revision received: 4 June 2019
Accepted: 19 June 2019
Published online: 16 August 2019
Published in print: October 01, 2019

Keywords

  1. Chronic Psychiatric Illness
  2. Genetics
  3. Schizophrenia
  4. Cognitive Neuroscience

Authors

Affiliations

Amanda B. Zheutlin, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Jessica Dennis, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Richard Karlsson Linnér, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Arden Moscati, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Nicole Restrepo, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Peter Straub, M.S.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Douglas Ruderfer, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Victor M. Castro
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Chia-Yen Chen, Sc.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Tian Ge, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Laura M. Huckins, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Alexander Charney, M.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
H. Lester Kirchner, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Eli A. Stahl, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Christopher F. Chabris, Ph.D.
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Lea K. Davis, Ph.D. [email protected]
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).
Jordan W. Smoller, M.D., Sc.D. [email protected]
Psychiatric and Neurodevelopmental Genetics Unit (Zheutlin, Chen, Ge, Smoller) and Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston (Chen); Stanley Center for Psychiatric Research, Broad Institute, Cambridge, Mass. (Zheutlin, Chen, Stahl, Smoller); Division of Genetic Medicine, Department of Medicine (Dennis, Straub, Ruderfer, Davis), Vanderbilt Genetics Institute (Dennis, Straub, Ruderfer, Davis), and Department of Biomedical Informatics (Ruderfer), Vanderbilt University Medical Center, Nashville; Department of Economics, School of Business and Economics, Vrije Universiteit Amsterdam, Amsterdam (Karlsson Linnér); Autism and Developmental Medicine Institute, Geisinger, Lewisburg, Pa. (Karlsson Linnér, Chabris); Charles Bronfman Institute for Personalized Medicine (Moscati), Pamela Sklar Division of Psychiatric Genomics (Huckins, Charney, Stahl), and Department of Genetics and Genomic Sciences (Huckins, Charney, Stahl, ), Icahn School of Medicine at Mount Sinai, New York; Department of Biomedical and Translational Informatics, Geisinger, Rockville, Md. (Restrepo, Kirchner); Research Information Science and Computing, Partners HealthCare, Somerville, Mass. (Castro).

Notes

Send correspondence to Dr. Smoller ([email protected]) and Dr. Davis ([email protected]).

Competing Interests

Dr. Smoller is an unpaid member of the Bipolar/Depression Research Community Advisory Panel of 23andMe. Dr. Kirchner has received funding from Regeneron Genetics Center as part of the DiscovEHR study. All other authors report no financial relationships with commercial interests.

Funding Information

National Heart, Lung, and Blood Institutehttp://dx.doi.org/10.13039/100000050: U19HL065962
National Institute of General Medical Sciencesehttp://dx.doi.org/10.13039/100000057: P50GM115305
National Eye Institutehttp://dx.doi.org/10.13039/100000053: P30EY08126
National Institute of Mental Healthhttp://dx.doi.org/10.13039/100000025: R01MH095034, R01MH106531, R01MH111776, R01MH113362, R01MH118233, U01MH109536
National Center for Research Resourceshttp://dx.doi.org/10.13039/100000097: S10RR025141, UL1RR024975
National Cancer Institutehttp://dx.doi.org/10.13039/100000054: P30CA068485
National Human Genome Research Institutehttp://dx.doi.org/10.13039/100000051: U01HG008679, U01HG008685
Canadian Institutes of Health Researchhttp://dx.doi.org/10.13039/501100000024: MFE-142936
National Center for Advancing Translational Scienceshttp://dx.doi.org/10.13039/100006108: UL1TR000445, UL1TR002243
Supported in part by NIMH grant R01MH118233 (to Drs. Smoller and Davis). Dr. Ge was supported in part by National Institute on Aging grant K99AG054573, Dr. Dennis was supported by the Canadian Institutes of Health Research (MFE-142936), Dr. Stahl was supported in part by NIMH grants U01MH109536, R01MH106531, and R01MH095034, Dr. Davis was supported by NIMH grant R01MH113362, Dr. Ruderfer was supported by NIMH grant R01MH111776, and Dr. Smoller was supported in part by National Human Genome Research Institute grant U01HG008685 supporting the eMERGE Network; he is also a Tepper Family MGH Research Scholar and is supported in part by the Demarest Lloyd, Jr. Foundation.

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