Nature Genetics
11, 321 - 324 (1995)
doi:10.1038/ng1195-321
An international two−stage genome−wide search for schizophrenia susceptibility genesH.W. Moises1, L. Yang1, H. Kristbjarnarson2, C. Wiese1, W. Byerley3, F. Macciardi4, V. Arolt5, D. Blackwood6, X. Liu7, B. Sjögren8, H.N. Aschauer9, H.-G. Hwu10, K. Jang11, W.J. Livesley11, J.L. Kennedy12, T. Zoega2, O. Ivarsson2, M.-T. Bui1, M.-H. Yu1, B. Havsteen13, D. Commenges14, J. Weissenbach15, E. Schwinger16, I.I. Gottesman17, A.J. Pakstis18, L. Wetterberg8, K.K. Kidd18
& T. Helgason2
1Dept. of Psych., Kiel Univ Hosp., Niemannsweg 147, 24105 Kiel Germany
2Dept. of Psych., Natl Univ Hosp., 121 Reykjavik, Iceland
3Dept. of Psych., Univ. of Utah, Salt Lake City, UT 84132, USA
4Dept. of Neurosci., Scientific Inst. Hosp. St. Raffael, Univ. of Milan, Milan 20127, Italy
5Dept. of Psych., Med. Univ. at Lübeck, 23538 Lübeck, Germany
6Dept. of Psych., Univ. of Edinburgh, Edinburgh EH10 5HF, UK
7Dept. of Psych. Research, West China Univ. of Med. Sci., Chengdu, Sichuan 610041, China
8Dept. of Psych., Karolinska Inst., St. Göran's Hosp., 11281 Stockholm, Sweden
9Dept. of General Psych., Vienna Univ. Hosp., 1090 Vienna, Austria
10Dept. of Psych., Natl. Taiwan Univ. Hosp., Taipei, Taiwan 100
11Dept. of Psych., Univ. of British Columbia, Vancouver, BC V6T 2A1, Canada
12Clarke Inst. of Psych., Univ. of Toronto, Ontario M5T 1R8, Canada
13Dept. of Biochem., Kiel Univ., 24118 Kiel, Germany
14I'INSERM, Université de Bordeaux II, Bordeaux, France
15Généthon, 91000 Evry, France
16Dept. of Human Genetics, Med Univ at Lübeck, 23538 Lübeck, Germany
17Dept. of Psych., Univ. of Virginia, Charlottesville, VA 22903, USA
18Dept. of Genetics, Yale Univ. School of Medicine, New Haven, CT 06510, USA Correspondence should be addressed to H.W.M. Schizophrenia is thought to be a multifactorial disease with complex mode of inheritance1,2. Using a two-stage strategy for another complex disorder, a number of putative IDDM-susceptibility genes have recently been mapped3. We now report the results of a two-stage genome-wide search for genes conferring susceptibility to schizophrenia. In stage I, model-free linkage analyses of large pedigrees from Iceland, a geographical isolate, revealed 26 loci suggestive of linkage. In stage II, ten of these were followed-up in a second international collaborative study comprising families from Austria, Canada, Germany, Italy, Scotland, Sweden, Taiwan and the United States. Potential linkage findings of stage I on chromosomes 6p, 9 and 20 were observed again in the second sample. Furthermore, in a third sample from China, fine mapping of the 6p region by association studies also showed evidence for linkage or linkage disequilibrium. Combining our results with other recent findings4,5 revealed significant evidence for linkage to an area distal of the HLA region on chromosome 6p. However, in a fourth sample from Europe, the 6p fine mapping finding observed in the Chinese sample could not be replicated. Finally, evidence suggestive of locus heterogeneity and oligogenic transmission in schizophrenia was obtained.
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