Human Molecular Genetics, 2001, Vol. 10, No. 15 1611-1617
© 2001 Oxford University Press
Chromosome 1 loci in Finnish schizophrenia families
1Department of Molecular Medicine and 2Department of Mental Health and Alcohol Research, National Public Health Institute, Helsinki, Finland, 3Millennium Pharmaceuticals Inc., Cambridge, MA, USA, 4Department of Human Genetics and 5Department of Biomathematics, UCLA, Los Angeles, CA, USA
We have earlier reported evidence for linkage to two regions on chromosome 1q32–q42 in schizophrenia families collected for two separate studies in Finland. Here we report the results of a fine mapping effort aimed at further definition of the chromosomal region of interest using a large, population-based study sample (221 families, 557 affected individuals). Most affecteds (78%) had a DSM-IV schizophrenia diagnosis and the remaining had schizophrenia spectrum disorders. We genotyped a total of 147 microsatellite markers on a wide 45 cM region of chromosome 1q. The results were analyzed separately for families originating from an internal isolate of Finland and for families from the rest of Finland, as well as for all families jointly. We used traditional two-point linkage analysis, SimWalk2 multipoint analysis and a novel gamete-competition association/linkage method. Evidence for linkage was obtained for one locus in the combined sample (Zmax = 2.71, D1S2709) and in the nuclear families from outside the internal isolate (Zmax = 3.21, D1S2709). In the families from the internal isolate the strongest evidence for linkage was obtained with markers located 22 cM centromeric from this marker (Zmax = 2.30, D1S245). Multipoint analysis also indicated these loci. Some evidence for association with several markers was observed using the gamete-competition method. Interestingly, the strongest evidence for linkage in the combined study sample was obtained for marker D1S2709, which is an intragenic marker of the DISC1 gene, previously suggested as a susceptibility gene for schizophrenia. These results are consistent with the presence of susceptibility gene(s) in this chromosomal region, a result also implied in other recent family studies of schizophrenia.
+ To whom correspondence should be addressed at present address: Department of Human Genetics, UCLA School of Medicine, 33-257 CHS, Box 851737, Los Angeles, CA 90095-1737, USA. Tel: +1 310 794 5631; Fax: +1 310 794 5446; Email: lpeltonen@mednet.ucla.edu
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  E. Ivleva, G. Thaker, and C. A. Tamminga Comparing Genes and Phenomenology in the Major Psychoses: Schizophrenia and Bipolar 1 Disorder Schizophr Bull, July 1, 2008; 34(4): 734 - 742. [Full Text] [PDF]
|
|
|
|
 |
|
 R. H. Perlis, S. Purcell, J. Fagerness, A. Kirby, T. L. Petryshen, J. Fan, and P. Sklar Family-Based Association Study of Lithium-Related and Other Candidate Genes in Bipolar Disorder Arch Gen Psychiatry, January 1, 2008; 65(1): 53 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. M. Palo, M. Antila, K. Silander, W. Hennah, H. Kilpinen, P. Soronen, A. Tuulio-Henriksson, T. Kieseppa, T. Partonen, J. Lonnqvist, et al. Association of distinct allelic haplotypes of DISC1 with psychotic and bipolar spectrum disorders and with underlying cognitive impairments Hum. Mol. Genet., October 15, 2007; 16(20): 2517 - 2528. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Ni, J. Valente, M. H Azevedo, M. T Pato, C. N Pato, and J. L Kennedy Connexin 50 gene on human chromosome 1q21 is associated with schizophrenia in matched case control and family-based studies J. Med. Genet., August 1, 2007; 44(8): 532 - 536. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Owen, N. Craddock, and A. Jablensky The Genetic Deconstruction of Psychosis Schizophr Bull, July 1, 2007; 33(4): 905 - 911. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hennah, L. Tomppo, T. Hiekkalinna, O. M. Palo, H. Kilpinen, J. Ekelund, A. Tuulio-Henriksson, K. Silander, T. Partonen, T. Paunio, et al. Families with the risk allele of DISC1 reveal a link between schizophrenia and another component of the same molecular pathway, NDE1 Hum. Mol. Genet., March 1, 2007; 16(5): 453 - 462. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. McClellan, E. Susser, and M.-C. King Schizophrenia: a common disease caused by multiple rare alleles The British Journal of Psychiatry, March 1, 2007; 190(3): 194 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. C. Roberts Schizophrenia in Translation: Disrupted in Schizophrenia (DISC1): Integrating Clinical and Basic Findings Schizophr Bull, January 1, 2007; 33(1): 11 - 15. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Hashimoto, T. Numakawa, T. Ohnishi, E. Kumamaru, Y. Yagasaki, T. Ishimoto, T. Mori, K. Nemoto, N. Adachi, A. Izumi, et al. Impact of the DISC1 Ser704Cys polymorphism on risk for major depression, brain morphology and ERK signaling Hum. Mol. Genet., October 15, 2006; 15(20): 3024 - 3033. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Gogos and D. J. Gerber Schizophrenia Susceptibility Genes: Emergence of Positional Candidates and Future Directions Focus, August 1, 2006; 4(3): 369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hennah, P. Thomson, L. Peltonen, and D. Porteous Genes and Schizophrenia: Beyond Schizophrenia: The Role of DISC1 in Major Mental Illness Schizophr Bull, July 1, 2006; 32(3): 409 - 416. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. MUIR, B. S. PICKARD, and D. H. R. BLACKWOOD Chromosomal abnormalities and psychosis The British Journal of Psychiatry, June 1, 2006; 188(6): 501 - 503. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. K. Lipska, T. Peters, T. M. Hyde, N. Halim, C. Horowitz, S. Mitkus, C. S. Weickert, M. Matsumoto, A. Sawa, R. E. Straub, et al. Expression of DISC1 binding partners is reduced in schizophrenia and associated with DISC1 SNPs Hum. Mol. Genet., April 15, 2006; 15(8): 1245 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Peltonen, M. Perola, J. Naukkarinen, and A. Palotie Lessons from studying monogenic disease for common disease. Hum. Mol. Genet., April 15, 2006; 15(suppl_1): R67 - R74. [Full Text] [PDF]
|
|
|
|
|
|
M. E Talkowski, K. Chowdari, D. A Lewis, and V. L Nimgaonkar Can RGS4 Polymorphisms Be Viewed as Credible Risk Factors for Schizophrenia? A Critical Review of the Evidence Schizophr Bull, April 1, 2006; 32(2): 203 - 208. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Craddock, M. C O'Donovan, and M. J Owen Genes for Schizophrenia and Bipolar Disorder? Implications for Psychiatric Nosology Schizophr Bull, January 1, 2006; 32(1): 9 - 16. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. D. Cannon, W. Hennah, T. G. M. van Erp, P. M. Thompson, J. Lonnqvist, M. Huttunen, T. Gasperoni, A. Tuulio-Henriksson, T. Pirkola, A. W. Toga, et al. Association of DISC1/TRAX Haplotypes With Schizophrenia, Reduced Prefrontal Gray Matter, and Impaired Short- and Long-term Memory Arch Gen Psychiatry, November 1, 2005; 62(11): 1205 - 1213. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. L. Hamshere, P. Bennett, N. Williams, R. Segurado, A. Cardno, N. Norton, D. Lambert, H. Williams, G. Kirov, A. Corvin, et al. Genomewide Linkage Scan in Schizoaffective Disorder: Significant Evidence for Linkage at 1q42 Close to DISC1, and Suggestive Evidence at 22q11 and 19p13 Arch Gen Psychiatry, October 1, 2005; 62(10): 1081 - 1088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Craddock, M C O'Donovan, and M J Owen The genetics of schizophrenia and bipolar disorder: dissecting psychosis J. Med. Genet., March 1, 2005; 42(3): 193 - 204. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Sawamura, T. Sawamura-Yamamoto, Y. Ozeki, C. A. Ross, and A. Sawa A form of DISC1 enriched in nucleus: Altered subcellular distribution in orbitofrontal cortex in psychosis and substance/alcohol abuse PNAS, January 25, 2005; 102(4): 1187 - 1192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Tuulio-Henriksson, T. Partonen, J. Suvisaari, J. Haukka, and J. Lonnqvist Age at onset and cognitive functioning in schizophrenia The British Journal of Psychiatry, September 1, 2004; 185(3): 215 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Paunio, A. Tuulio-Henriksson, T. Hiekkalinna, M. Perola, T. Varilo, T. Partonen, T. D. Cannon, J. Lonnqvist, and L. Peltonen Search for cognitive trait components of schizophrenia reveals a locus for verbal learning and memory on 4q and for visual working memory on 2q Hum. Mol. Genet., August 15, 2004; 13(16): 1693 - 1702. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Hennah, T. Varilo, M. Kestila, T. Paunio, R. Arajarvi, J. Haukka, A. Parker, R. Martin, S. Levitzky, T. Partonen, et al. Haplotype transmission analysis provides evidence of association for DISC1 to schizophrenia and suggests sex-dependent effects Hum. Mol. Genet., December 1, 2003; 12(23): 3151 - 3159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Sawa and A. Kamiya Elucidating the pathogenesis of schizophrenia BMJ, September 20, 2003; 327(7416): 632 - 633. [Full Text] [PDF]
|
|
|
|
|
|
J. A. Morris, G. Kandpal, L. Ma, and C. P. Austin DISC1 (Disrupted-In-Schizophrenia 1) is a centrosome-associated protein that interacts with MAP1A, MIPT3, ATF4/5 and NUDEL: regulation and loss of interaction with mutation Hum. Mol. Genet., July 1, 2003; 12(13): 1591 - 1608. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Miyamoto, A. S. LaMantia, G. E. Duncan, P. Sullivan, J. H. Gilmore, and J. A. Lieberman Recent Advances in the Neurobiology of Schizophrenia Mol. Interv., February 1, 2003; 3(1): 27 - 39. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. K. Millar, P. A. Thomson, N. R. Wray, W. J. Muir, D. H. R. Blackwood, and D. J. Porteous Response to Amar J. Klar: The Chromosome 1;11 Translocation Provides the Best Evidence Supporting Genetic Etiology for Schizophrenia and Bipolar Affective Disorders Genetics, February 1, 2003; 163(2): 833 - 835. [Full Text] [PDF]
|
|
|
|
|
|
A. J. S. Klar Response to Millar et al. Critique of Chromosome 1;11 Translocation Causing Psychosis Genetics, February 1, 2003; 163(2): 837 - 838. [Full Text] [PDF]
|
|
|
|
|
|
Y. Ozeki, T. Tomoda, J. Kleiderlein, A. Kamiya, L. Bord, K. Fujii, M. Okawa, N. Yamada, M. E. Hatten, S. H. Snyder, et al. From the Cover: Disrupted-in-Schizophrenia-1 (DISC-1): Mutant truncation prevents binding to NudE-like (NUDEL) and inhibits neurite outgrowth PNAS, January 7, 2003; 100(1): 289 - 294. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Macgregor, P. M. Visscher, S. Knott, D. Porteous, W. Muir, K. Millar, D. Blackwood, A. S. Bassett, E. W. C. Chow, V. J. Vieland, et al. Is Schizophrenia Linked to Chromosome 1q? Science, December 20, 2002; 298(5602): 2277a - 2277. [Full Text] [PDF]
|
|
|
|
|
|
A. Sawa and S. H. Snyder Schizophrenia: Diverse Approaches to a Complex Disease Science, April 26, 2002; 296(5568): 692 - 695. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. F. Levinson, P. A. Holmans, C. Laurent, B. Riley, A. E. Pulver, P. V. Gejman, S. G. Schwab, N. M. Williams, M. J. Owen, D. B. Wildenauer, et al. No Major Schizophrenia Locus Detected on Chromosome 1q in a Large Multicenter Sample Science, April 26, 2002; 296(5568): 739 - 741. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Paunio, J. Ekelund, T. Varilo, A. Parker, I. Hovatta, J. A. Turunen, K. Rinard, A. Foti, J. D. Terwilliger, H. Juvonen, et al. Genome-wide scan in a nationwide study sample of schizophrenia families in Finland reveals susceptibility loci on chromosomes 2q and 5q Hum. Mol. Genet., December 1, 2001; 10(26): 3037 - 3048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Pagani, R. Pariyarath, R. Garcia, C. Stuani, A. B. Burlina, G. Ruotolo, M. Rabusin, and F. E. Baralle New lysosomal acid lipase gene mutants explain the phenotype of Wolman disease and cholesteryl ester storage disease J. Lipid Res., July 1, 1998; 39(7): 1382 - 1388. [Abstract] [Full Text]
|
|