Analysis of 94 Candidate Genes and 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia
- Tiffany A. Greenwood,
Ph.D. , - Laura C. Lazzeroni,
Ph.D. , - Sarah S. Murray,
Ph.D. , - Kristin S. Cadenhead,
M.D. , - Monica E. Calkins,
Ph.D. , - Dorcas J. Dobie,
M.D. , - Michael F. Green,
Ph.D. , - Raquel E. Gur,
M.D., Ph.D. , - Ruben C. Gur,
Ph.D. , - Gary Hardiman,
Ph.D. , - John R. Kelsoe,
M.D. , - Sherry Leonard,
Ph.D. , - Gregory A. Light,
Ph.D. , - Keith H. Nuechterlein,
Ph.D. , - Ann Olincy,
M.D. , - Allen D. Radant,
M.D. , - Nicholas J. Schork,
Ph.D. , - Larry J. Seidman,
Ph.D. , - Larry J. Siever,
M.D. , - Jeremy M. Silverman,
Ph.D. , - William S. Stone,
Ph.D. , - Neal R. Swerdlow,
M.D., Ph.D. , - Debby W. Tsuang,
M.D., M.Sc. , - Ming T. Tsuang,
M.D., Ph.D., D.Sc. , - Bruce I. Turetsky,
M.D. , - Robert Freedman,
M.D. , and - David L. Braff,
M.D.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
From the Department of Psychiatry, the Department of Medicine, and the Biomedical Genomics Laboratory, University of California at San Diego, La Jolla; the San Diego VA Healthcare System; Scripps Genomic Medicine and the Department of Molecular and Experimental Medicine, Scripps Research Institute, La Jolla, Calif.; the Department of Psychiatry and Behavioral Sciences and the Department of Pediatrics, Stanford University, Stanford, Calif.; the Department of Psychiatry, University of Pennsylvania, Philadelphia; the Department of Psychiatry and Behavioral Sciences, University of Washington, Seattle; the VA Puget Sound Health Care System, Seattle; the Department of Psychiatry and Biobehavioral Sciences, Geffen School of Medicine, UCLA; the Department of Psychiatry, University of Colorado Health Sciences Center, Denver; the Department of Psychiatry, Harvard Medical School and the Harvard Institute of Psychiatric Epidemiology and Genetics, Boston; the Mental Health Center Public Psychiatry Division, Beth Israel Deaconess Medical Center, Boston; the Department of Psychiatry, Mount Sinai School of Medicine, New York; and the James J. Peters VA Medical Center, New York.
Abstract
Objective:
The authors used a custom array of 1,536 single-nucleotide polymorphisms (SNPs) to interrogate 94 functionally relevant candidate genes for schizophrenia and identify associations with 12 heritable neurophysiological and neurocognitive endophenotypes in data collected by the Consortium on the Genetics of Schizophrenia.
Method:
Variance-component association analyses of 534 genotyped subjects from 130 families were conducted by using Merlin software. A novel bootstrap total significance test was also developed to overcome the limitations of existing genomic multiple testing methods and robustly demonstrate significant associations in the context of complex family data and possible population stratification effects.
Results:
Associations with endophenotypes were observed for 46 genes of potential functional significance, with three SNPs at p<10–4, 27 SNPs at p<10–3, and 147 SNPs at p<0.01. The bootstrap analyses confirmed that the 47 SNP-endophenotype combinations with the strongest evidence of association significantly exceeded that expected by chance alone, with 93% of these findings expected to be true. Many of the genes interact on a molecular level, and eight genes (e.g., NRG1 and ERBB4) displayed evidence for pleiotropy, revealing associations with four or more endophenotypes. The results collectively support a strong role for genes related to glutamate signaling in mediating schizophrenia susceptibility.
Conclusions:
This study supports use of relevant endophenotypes and the bootstrap total significance test for identifying genetic variation underlying the etiology of schizophrenia. In addition, the observation of extensive pleiotropy for some genes and singular associations for others suggests alternative, independent pathways mediating pathogenesis in the “group of schizophrenias.”
