title: Genome-wide linkage analyses of 12 endophenotypes for schizophrenia from the Consortium on the Genetics of Schizophrenia.
abstract: 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.
  
  
  METHODS
  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.affiliation: Department of Psychiatry, University of California San Diego,La Jolla, Calif, USA.
authors.forename: Tiffany A
authors.initials: TA
authors.lastname: Greenwood
authors.forename: Neal R
authors.initials: NR
authors.lastname: Swerdlow
authors.forename: Raquel E
authors.initials: RE
authors.lastname: Gur
authors.forename: Kristin S
authors.initials: KS
authors.lastname: Cadenhead
authors.forename: Monica E
authors.initials: ME
authors.lastname: Calkins
authors.forename: Dorcas J
authors.initials: DJ
authors.lastname: Dobie
authors.forename: Robert
authors.initials: R
authors.lastname: Freedman
authors.forename: Michael F
authors.initials: MF
authors.lastname: Green
authors.forename: Ruben C
authors.initials: RC
authors.lastname: Gur
authors.forename: Laura C
authors.initials: LC
authors.lastname: Lazzeroni
authors.forename: Keith H
authors.initials: KH
authors.lastname: Nuechterlein
authors.forename: Ann
authors.initials: A
authors.lastname: Olincy
authors.forename: Allen D
authors.initials: AD
authors.lastname: Radant
authors.forename: Amrita
authors.initials: A
authors.lastname: Ray
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Schork
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Seidman
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Siever
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Silverman
authors.forename: William S
authors.initials: WS
authors.lastname: Stone
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Sugar
authors.forename: Debby W
authors.initials: DW
authors.lastname: Tsuang
authors.forename: Ming T
authors.initials: MT
authors.lastname: Tsuang
authors.forename: Bruce I
authors.initials: BI
authors.lastname: Turetsky
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Light
authors.forename: David L
authors.initials: DL
authors.lastname: Braff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D058068:Endophenotypes / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012559:Schizophrenia / Q000097:blood / Q000235:genetics*; D012565:Schizophrenic Psychology