Genome-wide scan in Portuguese Island families identifies 5q31-5q35 as a susceptibility locus for schizophrenia and psychosis

被引:93
作者
Sklar, P
Pato, MT
Kirby, A
Petryshen, TL
Medeiros, H
Carvalho, C
Macedo, A
Dourado, A
Coelho, I
Valente, J
Soares, MJ
Ferreira, CP
Lei, M
Verner, A
Hudson, TJ
Morley, CP
Kennedy, JL
Azevedo, MH
Lander, E
Daly, MJ
Pato, CN
机构
[1] Harvard Univ, Sch Med, Dept Psychiat, Charlestown, MA USA
[2] Massachusetts Gen Hosp, Psychiat & Neurodev Genet Unit, Charlestown, MA USA
[3] Broad Inst, Cambridge, MA USA
[4] Vet Adm, Syracuse, NY USA
[5] SUNY Upstate Med Univ, Ctr Psychiat & Mol Genet, Syracuse, NY USA
[6] Univ Coimbra, Coimbra, Portugal
[7] Psychiat Serv, Azores, Portugal
[8] McGill Univ, Montreal, PQ H3A 1A4, Canada
[9] Genome Quebec Innovat Ctr, Montreal, PQ H3A 1A4, Canada
[10] Ctr Addict & Mental Hlth, Clarke Div, Toronto, ON, Canada
关键词
schizophrenia; bipolar disorder; linkage; genetic;
D O I
10.1038/sj.mp.4001418
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Schizophrenia is a common psychiatric disorder with a complex genetic etiology. To understand the genetic basis of this syndrome in Portuguese Island populations, we performed a genome-wide scan of 29 families with schizophrenia, which identified a single region on 5q31 - 5q35 with strong linkage (NPL = 3.09, P = 0.0012 at D5S820). Empirical simulations set a genome-wide threshold of NPL = 3.10 for significant linkage. Additional support for this locus in schizophrenia comes from higher-density mapping and mapping of 11 additional families. The combined set of 40 families had a peak NPL = 3.28 ( P = 0.00066) at markers D5S2112 D5S820. These data and previous linkage findings from other investigators provide strong and consistent evidence for this genomic region as a susceptibility locus for schizophrenia. Exploratory analyses of a novel phenotype, psychosis, in families with schizophrenia and bipolar disorder detected evidence for linkage to the same markers as found in schizophrenia ( peak NPL = 3.03, P = 0.0012 at D5S820), suggesting that this locus may be responsible for the psychotic symptoms observed in both diseases.
引用
收藏
页码:213 / 218
页数:6
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