Nature Genetics
20, 70 - 73 (1998)
doi:10.1038/1734
Schizophrenia susceptibility loci on chromosomes 13q32 and 8p21Jean-Louis Blouin1, Beth A. Dombroski2, Swapan K. Nath3, Virginia K. Lasseter4, Paula S. Wolyniec4, Gerald Nestadt4, Mary Thornquist4, Gail Ullrich4, John McGrath4, Laura Kasch4, Malgorzata Lamacz4, Marion G. Thomas4, Corinne Gehrig1, Uppala Radhakrishna1, Sarah E. Snyder2, Katherine G. Balk2, Karin Neufeld4, Karen L. Swartz4, Nicola DeMarchi5, George N. Papadimitriou6, Dimitris G. Dikeos6, Costas N. Stefanis6, Aravinda Chakravarti3, Barton Childs4, David E. Housman7, Haig H. Kazazian2, Stylianos E. Antonarakis1
& Ann E. Pulver41
Division of Medical Genetics, University of Geneva
Medical School and Cantonal Hospital, Geneva, Switzerland
, 1211. 2
Department of Genetics, University of Pennsylvania
, Philadelphia, Pennsylvania 19104,
USA. 3
Department of Genetics and Center for Human Genetics,
Case Western Reserve University and University Hospitals of Cleveland,
Cleveland, Ohio 44106, USA. 4
Department of Psychiatry and Behavioral Sciences, The
Johns Hopkins School of Medicine, Baltimore, Maryland
21231, USA. 5
Seconda Universita di Napoli, Instituto di Psichiatria
, 80138, Napoli, Italy. 6
University Mental Health Research Institute, Eginition
Hospital, Athens, Greece, 115 28. 7
Center For Cancer Research, Massachusetts Institute
of Technology, Cambridge, Massachusetts 02139
, USA. J.-L.B., B.A.D. & S.K.N. contributed equally to
this work.
Correspondence should be addressed to Ann E. Pulver aepulver@welchlink.welch.jhu.eduSchizophrenia is a common disorder characterized by psychotic symptoms;
diagnostic criteria have been established1. Family, twin and
adoption studies suggest that both genetic and environmental factors influence
susceptibility (heritability is approximately 71%; ref.
2), however, little is known about the aetiology of schizophrenia.
Clinical and family studies suggest aetiological heterogeneity3,
6.
Previously, we reported that regions on chromosomes 22, 3 and 8 may be associated
with susceptibility to schizophrenia7,
8, and collaborations
provided some support for regions on chromosomes 8 and 22 (refs
9, 10, 11, 12, 13). We present here
a genome-wide scan for schizophrenia susceptibility loci (SSL) using 452 microsatellite
markers on 54 multiplex pedigrees. Non-parametric linkage (NPL) analysis provided
significant evidence for an SSL on chromosome 13q32 (NPL score = 4.18;
P = 0.00002), and suggestive evidence for another SSL on chromosome 8p21−22
(NPL = 3.64; P = 0.0001). Parametric linkage analysis provided additional
support for these SSL. Linkage evidence at chromosome 8 is weaker than that
at chromosome 13, so it is more probable that chromosome 8 may be a false
positive linkage. Additional putative SSL were noted on chromosomes 14q13
(NPL = 2.57; P = 0.005), 7q11 (NPL = 2.50, P = 0.007) and 22q11
(NPL = 2.42, P = 0.009). Verification of suggestive SSL on chromosomes
13q and 8p was attempted in a follow-up sample of 51 multiplex pedigrees.
This analysis confirmed the SSL in 13q14-q33 (NPL = 2.36, P = 0.007)
and supported the SSL in 8p22-p21 (NPL = 1.95, P = 0.023).
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