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Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23.
Am J Hum Genet. 2001 Mar; 68(3):661-73.AJ

Abstract

We have performed genetic linkage analysis in 13 large multiply affected families, to test the hypothesis that there is extensive heterogeneity of linkage for genetic subtypes of schizophrenia. Our strategy consisted of selecting 13 kindreds containing multiple affected cases in three or more generations, an absence of bipolar affective disorder, and a single progenitor source of schizophrenia with unilineal transmission into the branch of the kindred sampled. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10-cM intervals across the whole genome. We observed LOD scores >3.0 at five distinct loci, either in the sample as a whole or within single families, strongly suggesting etiological heterogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were found at 1q33.2 (LOD score 3.2; P=.0003), 5q33.2 (LOD score 3.6; P=.0001), 8p22.1-22 (LOD score 3.6; P=.0001), and 11q21 (LOD score 3.1; P=.0004). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P=.0003) and at 11q23.3-24 (LOD score 3.2; P=.0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia-susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequilibrium. Such studies will soon allow the identification of mutations having a direct effect on susceptibility to schizophrenia.

Authors+Show Affiliations

Molecular Psychiatry Laboratory, Department of Psychiatry and Behavioural Sciences, Windeyer Institute for Medical Sciences, Royal Free and University College London Medical School, London, W1T 4JF, United Kingdom. h.gurling@ucl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11179014

Citation

Gurling, H M., et al. "Genomewide Genetic Linkage Analysis Confirms the Presence of Susceptibility Loci for Schizophrenia, On Chromosomes 1q32.2, 5q33.2, and 8p21-22 and Provides Support for Linkage to Schizophrenia, On Chromosomes 11q23.3-24 and 20q12.1-11.23." American Journal of Human Genetics, vol. 68, no. 3, 2001, pp. 661-73.
Gurling HM, Kalsi G, Brynjolfson J, et al. Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23. Am J Hum Genet. 2001;68(3):661-73.
Gurling, H. M., Kalsi, G., Brynjolfson, J., Sigmundsson, T., Sherrington, R., Mankoo, B. S., Read, T., Murphy, P., Blaveri, E., McQuillin, A., Petursson, H., & Curtis, D. (2001). Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23. American Journal of Human Genetics, 68(3), 661-73.
Gurling HM, et al. Genomewide Genetic Linkage Analysis Confirms the Presence of Susceptibility Loci for Schizophrenia, On Chromosomes 1q32.2, 5q33.2, and 8p21-22 and Provides Support for Linkage to Schizophrenia, On Chromosomes 11q23.3-24 and 20q12.1-11.23. Am J Hum Genet. 2001;68(3):661-73. PubMed PMID: 11179014.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23. AU - Gurling,H M, AU - Kalsi,G, AU - Brynjolfson,J, AU - Sigmundsson,T, AU - Sherrington,R, AU - Mankoo,B S, AU - Read,T, AU - Murphy,P, AU - Blaveri,E, AU - McQuillin,A, AU - Petursson,H, AU - Curtis,D, PY - 2000/12/27/received PY - 2001/01/12/accepted PY - 2001/2/17/pubmed PY - 2001/4/6/medline PY - 2001/2/17/entrez SP - 661 EP - 73 JF - American journal of human genetics JO - Am. J. Hum. Genet. VL - 68 IS - 3 N2 - We have performed genetic linkage analysis in 13 large multiply affected families, to test the hypothesis that there is extensive heterogeneity of linkage for genetic subtypes of schizophrenia. Our strategy consisted of selecting 13 kindreds containing multiple affected cases in three or more generations, an absence of bipolar affective disorder, and a single progenitor source of schizophrenia with unilineal transmission into the branch of the kindred sampled. DNA samples from these families were genotyped with 365 microsatellite markers spaced at approximately 10-cM intervals across the whole genome. We observed LOD scores >3.0 at five distinct loci, either in the sample as a whole or within single families, strongly suggesting etiological heterogeneity. Heterogeneity LOD scores >3.0 in the sample as a whole were found at 1q33.2 (LOD score 3.2; P=.0003), 5q33.2 (LOD score 3.6; P=.0001), 8p22.1-22 (LOD score 3.6; P=.0001), and 11q21 (LOD score 3.1; P=.0004). LOD scores >3.0 within single pedigrees were found at 4q13-31 (LOD score 3.2; P=.0003) and at 11q23.3-24 (LOD score 3.2; P=.0003). A LOD score of 2.9 was also found at 20q12.1-11.23 within in a single family. The fact that other studies have also detected LOD scores >3.0 at 1q33.2, 5q33.2, 8p21-22 and 11q21 suggests that these regions do indeed harbor schizophrenia-susceptibility loci. We believe that the weight of evidence for linkage to the chromosome 1q22, 5q33.2, and 8p21-22 loci is now sufficient to justify intensive investigation of these regions by methods based on linkage disequilibrium. Such studies will soon allow the identification of mutations having a direct effect on susceptibility to schizophrenia. SN - 0002-9297 UR - https://www.unboundmedicine.com/medline/citation/11179014/Genomewide_genetic_linkage_analysis_confirms_the_presence_of_susceptibility_loci_for_schizophrenia_on_chromosomes_1q32_2_5q33_2_and_8p21_22_and_provides_support_for_linkage_to_schizophrenia_on_chromosomes_11q23_3_24_and_20q12_1_11_23_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)63106-1 DB - PRIME DP - Unbound Medicine ER -