The gene hunters' findings, published in the April 26 issue of Science, highlight the challenge of identifying the genetic roots of complex diseases. "Schizophrenia is a complex psychiatric disorder," says Pulver. "It can't be explained by either a single altered gene or a single environmental cause. There are clearly genetic components, but they are likely to be varied and to interact in many ways with non-genetic factors."
Recent studies had suggested that genes associated with susceptibility to schizophrenia would be found on the "q" or long arm of chromosome 1, a region separated from the short arm, known as "p."
In their study, Pulver and colleagues searched for associations between genetic markers on chromosome 1 and schizophrenia in families that have more than one member with the disease. This approach, called genetic linkage analysis, is used to detect the location on the chromosome where disease genes reside.
"By pooling our resources and data, and agreeing on how to attack the problem in a large sample of affected families, we were able to quickly use this type of genetic linkage analysis to tell if we were on the right track," says Pulver.
It's still possible that genes on chromosome 1q contribute to the disease, she says, but these would influence only a small proportion of patients. "Biology is complicated, and the search for genes that contribute to large numbers of cases continues," she says.
"This paper highlights the difficulty of unraveling complex diseases," says Solomon Snyder, M.D., professor of neuroscience at Hopkins and author of a review article in the same issue of Science, with Akira Sawa, M.D., Ph.D., on schizophrenia research.
Snyder points out that a variety of genetic and environmental factors are at play in cancer, cardiovascular disorders and diabetes. "Despite the difficulties," says Snyder, "we are getting closer to understanding the molecular causes of schizophrenia. Advances in imaging, neuroanatomy, genetic analysis and psychopharmacology are being applied in earnest to this debilitating disease."
The study was funded by the National Institute of Mental Health, Medical Research Council (UK), Deutsche Forschungsfemeinschaft, the German-Israeli Foundation for Scientific Research, the National Health and Medical Research Council of Australia, and the Centre National de la Recherche Scientifique. The lead author of the study is Douglas Levinson, Department of Psychiatry, University of Pennsylvania. Other Hopkins scientists involved in the study are Gerald Nestadt, M.D., and Kung Yee Liang, Ph.D.
On the Web:
The Johns Hopkins Department of Psychiatry and Behavioral Sciences: http://www.
The Johns Hopkins Genetic Schizophrenia Epidemiology Program: http://www.
The Johns Hopkins Department of Neuroscience:
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