Schizophrenia susceptibility genes: emergence of positional candidates and future directions

被引:74
作者
Gogos, JA [1 ]
Gerber, DJ
机构
[1] Columbia Univ, Coll Phys & Surg, Dept Physiol & Cellular Biophys, New York, NY 10032 USA
[2] Columbia Univ, Coll Phys & Surg, Ctr Neurobiol & Behav, New York, NY 10032 USA
[3] Galenea Corp, Cambridge, MA 02139 USA
关键词
D O I
10.1016/j.tips.2006.02.005
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Schizophrenia is a devastating psychiatric disorder that affects similar to 1% of the population worldwide. It is characterized by so-called 'positive symptoms' - including delusions and hallucinations - 'negative symptoms' including blunted emotions and social isolation - and cognitive deficits - including impairments in attention and working memory. Studies of the inheritance of schizophrenia have revealed that it is a multifactorial disease that is characterized by multiple genetic susceptibility elements, each contributing a modest degree of risk. Linkage studies have identified several potential schizophrenia susceptibility loci, and in recent years major progress has been made in the identification of positional candidate susceptibility genes from these loci. A central goal of future research will be to use this genetic knowledge to generate specific animal models, characterize genetic interactions, investigate the disease pathophysiology and assist drug-discovery efforts.
引用
收藏
页码:226 / 233
页数:8
相关论文
共 99 条
[1]   Polymorphisms in the 13q33.2 gene G72/G30 are associated with childhood-onset schizophrenia and psychosis not otherwise specified [J].
Addington, AM ;
Gornick, M ;
Sporn, AL ;
Gogtay, N ;
Greenstein, D ;
Lenane, M ;
Gochman, P ;
Baker, N ;
Balkissoon, R ;
Vakkalanka, RK ;
Weinberger, DR ;
Straub, RE ;
Rapoport, JL .
BIOLOGICAL PSYCHIATRY, 2004, 55 (10) :976-980
[2]   Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia [J].
Badner, JA ;
Gershon, ES .
MOLECULAR PSYCHIATRY, 2002, 7 (04) :405-411
[3]   Functional consequences of PRODH missense mutations [J].
Bender, HU ;
Almashanu, S ;
Steel, G ;
Hu, CA ;
Lin, WW ;
Willis, A ;
Pulver, A ;
Valle, D .
AMERICAN JOURNAL OF HUMAN GENETICS, 2005, 76 (03) :409-420
[4]   Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain [J].
Benson, MA ;
Newey, SE ;
Martin-Rendon, E ;
Hawkes, R ;
Blake, DJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (26) :24232-24241
[5]   Trace amines: Identification of a family of mammalian G protein-coupled receptors [J].
Borowsky, B ;
Adham, N ;
Jones, KA ;
Raddatz, R ;
Artymyshyn, R ;
Ogozalek, KL ;
Durkin, MM ;
Lakhlani, PP ;
Bonini, JA ;
Pathirana, S ;
Boyle, N ;
Pu, XS ;
Kouranova, E ;
Lichtblau, H ;
Ochoa, FY ;
Branchek, TA ;
Gerald, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (16) :8966-8971
[6]   A haplotype implicated in schizophrenia susceptibility is associated with reduced COMT expression in human brain [J].
Bray, NJ ;
Buckland, PR ;
Williams, NM ;
Williams, HJ ;
Norton, N ;
Owen, MJ ;
O'Donovan, MC .
AMERICAN JOURNAL OF HUMAN GENETICS, 2003, 73 (01) :152-161
[7]   Location of a major susceptibility locus for familiar schizophrenia on chromosome 1q21-q22 [J].
Brzustowicz, LM ;
Hodgkinson, KA ;
Chow, EWC ;
Honer, WG ;
Bassett, AS .
SCIENCE, 2000, 288 (5466) :678-682
[8]   Linkage disequilibrium mapping of schizophrenia susceptibility to the CAPON region of chromosome 1q22 [J].
Brzustowicz, LM ;
Simone, J ;
Mohseni, P ;
Hayter, JE ;
Hodgkinson, KA ;
Chow, EWC ;
Bassett, AS .
AMERICAN JOURNAL OF HUMAN GENETICS, 2004, 74 (05) :1057-1063
[9]   Variation in DISC1 affects hippocampal structure and function and increases risk for schizophrenia [J].
Callicott, JH ;
Straub, RE ;
Pezawas, L ;
Egan, MF ;
Mattay, VS ;
Hariri, AR ;
Verchinski, BA ;
Meyer-Lindenberg, A ;
Balkissoon, R ;
Kolachana, B ;
Goldberg, TE ;
Weinberger, DR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (24) :8627-8632
[10]   Demonstrating stratification in a European American population [J].
Campbell, CD ;
Ogburn, EL ;
Lunetta, KL ;
Lyon, HN ;
Freedman, ML ;
Groop, LC ;
Altshuler, D ;
Ardlie, KG ;
Hirschhorn, JN .
NATURE GENETICS, 2005, 37 (08) :868-872