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Genome-Wide Linkage Analyses of 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia.

Genome-Wide Linkage Analyses of 12 Endophenotypes for Schizophrenia From the Consortium on the Genetics of Schizophrenia.

Authors :
Greenwood, Tiffany A.
Swerdlow, Neal R.
Gur, Raquel E.
Cadenhead, Kristin S.
Calkins, Monica E.
Dobie, Dorcas J.
Freedman, Robert
Green, Michael F.
Gur, Ruben C
lazzeroni, taura C.
Nuechterlein, Keith H.
Oiincy, Ann
Radant, Allen D.
Ray, Amrita
Schork, Nicholas J.
Seidman, Larry J.
Siever, Larry J.
Silverman, Jeremy M.
Stone, William S.
Sugar, Catherine A.
Source :
American Journal of Psychiatry; May2013, Vol. 170 Issue 5, p521-532, 12p
Publication Year :
2013

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. 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 singlenucleotide polymorphisms that were successfully assayed, 5,760 of which were common to both phases, were conducted using both variance components and pedigreewide 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 degradedstimulus 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. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
0002953X
Volume :
170
Issue :
5
Database :
Complementary Index
Journal :
American Journal of Psychiatry
Publication Type :
Academic Journal
Accession number :
87663223
Full Text :
https://doi.org/10.1176/appi.ajp.2012.12020186