Stassen
Fakultäten » Medizinische Fakultät » Psychiatrische Universitätsklinik » Affektive Erkrankungen und Allgemeinpsychiatrie Zürich Ost, Klinik für » Prof. Dr. Daniel Hell (emeritiert) » Stassen
Completed research project
| Title / Titel | Oligogenic Predisposition to Alcohol Dependence and Comorbidity with Psychiatric Disorders | ||||||||
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| Abstract (PDF, 14 KB) | |||||||||
| Summary / Zusammenfassung | Using data from a two stage family study (totally 255 families, 1102 genotyped subjects) we searched for an ethnicity-independent oligogenic configuration of interacting loci that explained the observed susceptibility to alcohol dependence. Our analyses were carried out under the constraint of reproducibility as during the adaptive search one set of families served as "training" samples while the second set of families were used as independent "test" samples. Based on a genetic similarity function that quantifies the genetic distances d(xi,xj) between feature vectors xi, xj made up by the allelic patterns of any two subjects i, j at n loci l1, l2, .. ln, our signal detection algorithm looked for significant differences between the parent-offspring similarities and the between-sib similarities of affected sib pairs under the constraint that no such differences showed up for the unaffected sib pairs. The question of unknown population admixture was addressed by means of a quantitative concept of ethnicity in combination with cluster-analytical methods. We found a reproducible configuration of 14 ethnicity-independent loci on chromosomes 1, 2, 4, 9, 12, 13, 14, 16, 18 and 20 as being vulnerability-related, and 5 ethnicity-independent loci on chromosomes 1, 5, 14 and 19 as being protective with respect to the clinical syndrome of alcohol dependence. None of these loci appeared to be, by itself, necessary or sufficient for the observed susceptibility to alcohol dependence. Weitere Informationen |
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| Publications / Publikationen | Stassen HH, Begleiter H, Porjesz B, Rice J, Scharfetter C, Reich T: Structural decomposition of genetic diversity in families with alcohol dependence. In: Goldin L, Amos CI, Chase GA, Goldstein AM, Jarvik GP, Martinez MM, Suarez BK, Weeks DE, Wijsman EM, MacCluer JW; Genetic Analysis Workshop 11: Analysis of genetic and environmental factors in common diseases. Genetic Epidemiology 1999; 17 Suppl: 325-330Hinrichs T, Culverhouse R, Foroud T, Stassen HH, Begleiter H, Reich T: Replication: the need for matched data, part I. Am. J. Med. Genetics; Neuropsychiatric Genetics 2000; 96,4: 569Weitere Informationen | ||||||||
| Keywords / Suchbegriffe | Alcohol dependence, vulnerability and protection factors, genetic diversity, population admixture, epistasis | ||||||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
Foundation |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | May 1999 to May 2003 |