OBJECTIVE: The Consortium on the Genetics of Schizophrenia has undertaken a large multisite study to characterize 12 neurophysiological and neurocognitive endophenotypic measures as a step toward understanding the complex genetic basis of schizophrenia. The authors previously demonstrated the heritability of these endophenotypes; in the present study, genetic linkage was evaluated. METHOD: Each family consisted of a proband with schizophrenia, at least one unaffected sibling, and both parents. A total of 1,286 participants from 296 families were genotyped in two phases, and 1,004 individuals were also assessed for the endophenotypes. Linkage analyses of the 6,055 single-nucleotide polymorphisms that were successfully assayed, 5,760 of which were common to both phases, were conducted using both variance components and pedigree-wide regression methods. RESULTS: Linkage analyses of the 12 endophenotypes collectively identified one region meeting genome-wide significance criteria, with a LOD (log of odds) score of 4.0 on chromosome 3p14 for the antisaccade task, and another region on 1p36 nearly meeting genome-wide significance, with a LOD score of 3.5 for emotion recognition. Chromosomal regions meeting genome-wide suggestive criteria with LOD scores >2.2 were identified for spatial processing (2p25 and 16q23), sensorimotor dexterity (2q24 and 2q32), prepulse inhibition (5p15), the California Verbal Learning Test (8q24), the degraded-stimulus Continuous Performance Test (10q26), face memory (10q26 and 12p12), and the Letter-Number Span (14q23). CONCLUSIONS: Twelve regions meeting genome-wide significant and suggestive criteria for previously identified heritable, schizophrenia-related endophenotypes were observed, and several genes of potential neurobiological interest were identified. Replication and further genomic studies are needed to assess the biological significance of these results.
OBJECTIVE: The Consortium on the Genetics of Schizophrenia has undertaken a large multisite study to characterize 12 neurophysiological and neurocognitive endophenotypic measures as a step toward understanding the complex genetic basis of schizophrenia. The authors previously demonstrated the heritability of these endophenotypes; in the present study, genetic linkage was evaluated. METHOD: Each family consisted of a proband with schizophrenia, at least one unaffected sibling, and both parents. A total of 1,286 participants from 296 families were genotyped in two phases, and 1,004 individuals were also assessed for the endophenotypes. Linkage analyses of the 6,055 single-nucleotide polymorphisms that were successfully assayed, 5,760 of which were common to both phases, were conducted using both variance components and pedigree-wide regression methods. RESULTS: Linkage analyses of the 12 endophenotypes collectively identified one region meeting genome-wide significance criteria, with a LOD (log of odds) score of 4.0 on chromosome 3p14 for the antisaccade task, and another region on 1p36 nearly meeting genome-wide significance, with a LOD score of 3.5 for emotion recognition. Chromosomal regions meeting genome-wide suggestive criteria with LOD scores >2.2 were identified for spatial processing (2p25 and 16q23), sensorimotor dexterity (2q24 and 2q32), prepulse inhibition (5p15), the California Verbal Learning Test (8q24), the degraded-stimulus Continuous Performance Test (10q26), face memory (10q26 and 12p12), and the Letter-Number Span (14q23). CONCLUSIONS: Twelve regions meeting genome-wide significant and suggestive criteria for previously identified heritable, schizophrenia-related endophenotypes were observed, and several genes of potential neurobiological interest were identified. Replication and further genomic studies are needed to assess the biological significance of these results.
Authors: M Martinez; L R Goldin; Q Cao; J Zhang; A R Sanders; D J Nancarrow; J M Taylor; D F Levinson; A Kirby; R R Crowe; N C Andreasen; D W Black; J M Silverman; D P Lennon; D A Nertney; D M Brown; B J Mowry; E S Gershon; P V Gejman Journal: Am J Med Genet Date: 1999-08-20
Authors: Q Cao; M Martinez; J Zhang; A R Sanders; J A Badner; A Cravchik; C J Markey; E Beshah; J J Guroff; M E Maxwell; D M Kazuba; R Whiten; L R Goldin; E S Gershon; P V Gejman Journal: Genomics Date: 1997-07-01 Impact factor: 5.736
Authors: S Leonard; J Gault; T Moore; J Hopkins; M Robinson; A Olincy; L E Adler; C R Cloninger; C A Kaufmann; M T Tsuang; S V Faraone; D Malaspina; D M Svrakic; R Freedman Journal: Am J Med Genet Date: 1998-07-10
Authors: Stephanie M Perez; David D Aguilar; Jennifer L Neary; Melanie A Carless; Andrea Giuffrida; Daniel J Lodge Journal: Neuropsychopharmacology Date: 2015-06-12 Impact factor: 7.853
Authors: William S Stone; Raquelle I Mesholam-Gately; David L Braff; Monica E Calkins; Robert Freedman; Michael F Green; Tiffany A Greenwood; Raquel E Gur; Ruben C Gur; Laura C Lazzeroni; Gregory A Light; Keith H Nuechterlein; Ann Olincy; Allen D Radant; Larry J Siever; Jeremy M Silverman; Joyce Sprock; Catherine A Sugar; Neal R Swerdlow; Debby W Tsuang; Ming T Tsuang; Bruce I Turetsky; Larry J Seidman Journal: Schizophr Res Date: 2014-12-12 Impact factor: 4.939
Authors: Steven P Millard; Jane Shofer; David Braff; Monica Calkins; Kristin Cadenhead; Robert Freedman; Michael F Green; Tiffany A Greenwood; Raquel Gur; Ruben Gur; Laura C Lazzeroni; Gregory A Light; Ann Olincy; Keith Nuechterlein; Larry Seidman; Larry Siever; Jeremy Silverman; William S Stone; Joyce Sprock; Catherine A Sugar; Neal R Swerdlow; Ming Tsuang; Bruce Turetsky; Allen Radant; Debby W Tsuang Journal: Schizophr Res Date: 2016-04-28 Impact factor: 4.939