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PMID: 9758604 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Support for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis.

American journal of human genetics ·Vol. 63 ·No. 4 ·1998-10-00 ·Pages 1139-52

Schwab SG, Hallmayer J, Lerer B, Albus M, Borrmann M, Hönig S, Strauss M, Segman R, Lichtermann D, Knapp M, Trixler M, Maier W, Wildenauer DB

Abstract

The action of antipsychotic drugs on dopamine receptors suggests that dopaminergic signal transmission may play a role in the development of schizophrenia. We tested eight candidate genes (coding for dopamine receptors, the dopamine transporter, and G-proteins) in 59 families from Germany and Israel, for association. A P value of .00055 (.0044 when corrected for the no. of markers tested) was obtained for the intronic CA-repeat marker G-olfalpha on chromosome 18p. The value decreased to .000088 (.0007) when nine sibs with recurrent unipolar depressive disorder were included. Linkage analysis using SSLP markers densely spaced around G-olfalpha yielded a maximum two-point LOD score of 3.1 for a marker 0.5 cM distal to G-olfalpha. Multipoint analysis under the assumption of heterogeneity supported this linkage-whether the affected pheotype was defined narrowly or broadly-as did nonparametric linkage (NPL). In 12 families with exclusively maternal transmission of the disease, the NPL value also supported linkage to this marker. In order to test for association/linkage disequilibrium in the presence of linkage, the sample was restricted to independent offspring. When this sample was combined with 65 additional simplex families (each of them comprising one schizophrenic offspring and his or her parents), the 124-bp allele of G-olfalpha was transmitted 47 times and was not transmitted 21 times (P=.009). These results suggest the existence, on chromosome 18p, of a potential susceptibility locus for functional psychoses.

MeSH Terms
Chromosomes, Human, Pair 18/genetics Female GTP-Binding Protein alpha Subunits GTP-Binding Proteins/genetics Genetic Markers Genetic Predisposition to Disease Genotype Germany Heterotrimeric GTP-Binding Proteins Humans Israel Linkage Disequilibrium Lod Score Male Multivariate Analysis Psychotic Disorders/genetics Schizophrenia/genetics Sex Factors Statistics, Nonparametric
Chemicals
GTP-Binding Protein alpha Subunits Genetic Markers olfactory G protein subunit alpha olf GTP-Binding Proteins Heterotrimeric GTP-Binding Proteins
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Schwab S G
Molecular Genetics Laboratory, Department of Psychiatry, University of Bon, Germany.
Hallmayer J
Lerer B
Albus M
Borrmann M
Hönig S
Strauss M
Segman R
Lichtermann D
Knapp M
Trixler M
Maier W
Wildenauer D B
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/302046
Published
1998-10-00
Pages
1139-52
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1377479
Subset
IM
External Links
PubMed source DOI: 10.1086/302046 PMC Full Text View journal details
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