Location of a Major Susceptibility Locus for Familial Schizophrenia on Chromosome 1q21-q22

Overview

Journal Science

Specialty Science

Date 2000 Apr 28

PMID 10784452

Citations 119

Authors

L M Brzustowicz

K A Hodgkinson

E W Chow

W G Honer

A S Bassett

Affiliations

Soon will be listed here.

Abstract

Schizophrenia is a complex disorder, and there is substantial evidence supporting a genetic etiology. Despite this, prior attempts to localize susceptibility loci have produced predominantly suggestive findings. A genome-wide scan for schizophrenia susceptibility loci in 22 extended families with high rates of schizophrenia provided highly significant evidence of linkage to chromosome 1 (1q21-q22), with a maximum heterogeneity logarithm of the likelihood of linkage (lod) score of 6.50. This linkage result should provide sufficient power to allow the positional cloning of the underlying susceptibility gene.

Citing Articles

Synaptotagmin-11 deficiency mediates schizophrenia-like behaviors in mice via dopamine over-transmission.

Chen Y, Gu Y, Wang B, Wei A, Dong N, Jiang Y Nat Commun. 2024; 15(1):10571.

PMID: 39632880 PMC: 11618495. DOI: 10.1038/s41467-024-54604-4.

Gene Variants and Their Role in Metabolic Syndrome: A Study of Patients with Schizophrenia.

Mednova I, Pozhidaev I, Tiguntsev V, Bocharova A, Paderina D, Boiko A Biomedicines. 2024; 12(3).

PMID: 38540239 PMC: 10968077. DOI: 10.3390/biomedicines12030627.

The Gut-Brain Axis in Schizophrenia: The Implications of the Gut Microbiome and SCFA Production.

Ju S, Shin Y, Han S, Kwon J, Choi T, Kang I Nutrients. 2023; 15(20).

PMID: 37892465 PMC: 10610543. DOI: 10.3390/nu15204391.

and missense variants implicate defective neurotransmission in early-onset inherited schizophrenias.

Kanwal A, Pardo J, Naz S J Psychiatry Neurosci. 2022; 47(6):E379-E390.

PMID: 36318984 PMC: 9633053. DOI: 10.1503/jpn.220070.

Effects of psychosis-associated genetic markers on brain volumetry: a systematic review of replicated findings and an independent validation.

Vouga Ribeiro N, Tavares V, Bramon E, Toulopoulou T, Valli I, Shergill S Psychol Med. 2022; :1-16.

PMID: 36168994 PMC: 9811278. DOI: 10.1017/S0033291722002896.

References

Blouin J, Dombroski B, Nath S, Lasseter V, Wolyniec P, Nestadt G . Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21. Nat Genet. 1998; 20(1):70-3. DOI: 10.1038/1734. View

Risch N, Botstein D . A manic depressive history. Nat Genet. 1996; 12(4):351-3. DOI: 10.1038/ng0496-351. View

McGuffin P, Asherson P, Owen M, Farmer A . The strength of the genetic effect. Is there room for an environmental influence in the aetiology of schizophrenia?. Br J Psychiatry. 1994; 164(5):593-9. DOI: 10.1192/bjp.164.5.593. View

Dror V, Shamir E, Ghanshani S, Kimhi R, Swartz M, Barak Y . hKCa3/KCNN3 potassium channel gene: association of longer CAG repeats with schizophrenia in Israeli Ashkenazi Jews, expression in human tissues and localization to chromosome 1q21. Mol Psychiatry. 1999; 4(3):254-60. DOI: 10.1038/sj.mp.4000508. View

LANDER E, Kruglyak L . Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995; 11(3):241-7. DOI: 10.1038/ng1195-241. View

Brzustowicz L, Honer W, Chow E, Little D, Hogan J, Hodgkinson K . Linkage of familial schizophrenia to chromosome 13q32. Am J Hum Genet. 1999; 65(4):1096-103. PMC: 1288243. DOI: 10.1086/302579. View

Abreu P, Greenberg D, Hodge S . Direct power comparisons between simple LOD scores and NPL scores for linkage analysis in complex diseases. Am J Hum Genet. 1999; 65(3):847-57. PMC: 1377991. DOI: 10.1086/302536. View

Hovatta I, Varilo T, Suvisaari J, Terwilliger J, Ollikainen V, Arajarvi R . A genomewide screen for schizophrenia genes in an isolated Finnish subpopulation, suggesting multiple susceptibility loci. Am J Hum Genet. 1999; 65(4):1114-24. PMC: 1288245. DOI: 10.1086/302567. View

Levinson D, Mahtani M, Nancarrow D, Brown D, Kruglyak L, Kirby A . Genome scan of schizophrenia. Am J Psychiatry. 1998; 155(6):741-50. DOI: 10.1176/ajp.155.6.741. View

10.

Straub R, MacLean C, ONeill F, Walsh D, Kendler K . Support for a possible schizophrenia vulnerability locus in region 5q22-31 in Irish families. Mol Psychiatry. 1997; 2(2):148-55. DOI: 10.1038/sj.mp.4000258. View

11.

Fananas L, Fuster C, Guillamat R, Miro R . Chromosomal fragile site 1q21 in schizophrenic patients. Am J Psychiatry. 1997; 154(5):716. DOI: 10.1176/ajp.154.5.716a. View

12.

Detera-Wadleigh S, Badner J, Berrettini W, Yoshikawa T, Goldin L, Turner G . A high-density genome scan detects evidence for a bipolar-disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2. Proc Natl Acad Sci U S A. 1999; 96(10):5604-9. PMC: 21907. DOI: 10.1073/pnas.96.10.5604. View

13.

Durner M, Vieland V, Greenberg D . Further evidence for the increased power of LOD scores compared with nonparametric methods. Am J Hum Genet. 1999; 64(1):281-9. PMC: 1377726. DOI: 10.1086/302181. View

14.

Bassett A, Collins E, Nuttall S, Honer W . Positive and negative symptoms in families with schizophrenia. Schizophr Res. 1993; 11(1):9-19. PMC: 3188302. DOI: 10.1016/0920-9964(93)90033-f. View

15.

Risch N . Linkage strategies for genetically complex traits. I. Multilocus models. Am J Hum Genet. 1990; 46(2):222-8. PMC: 1684987. View

16.

OConnell J, Weeks D . The VITESSE algorithm for rapid exact multilocus linkage analysis via genotype set-recoding and fuzzy inheritance. Nat Genet. 1995; 11(4):402-8. DOI: 10.1038/ng1295-402. View

17.

Morton N . Significance levels in complex inheritance. Am J Hum Genet. 1998; 62(3):690-7. PMC: 1376937. DOI: 10.1086/301741. View

18.

Cottingham Jr R, Idury R, Schaffer A . Faster sequential genetic linkage computations. Am J Hum Genet. 1993; 53(1):252-63. PMC: 1682239. View

19.

Kosower N, Gerad L, Goldstein M, Parasol N, Zipser Y, Ragolsky M . Constitutive heterochromatin of chromosome 1 and Duffy blood group alleles in schizophrenia. Am J Med Genet. 1995; 60(2):133-8. DOI: 10.1002/ajmg.1320600209. View

20.

Risch N, GIUFFRA L . Model misspecification and multipoint linkage analysis. Hum Hered. 1992; 42(1):77-92. DOI: 10.1159/000154047. View