Abstract
We conducted a 10 centimorgan (cM) linkage genome scan in a set of American extended pedigrees ascertained through probands with panic disorder. Several anxiety disorders segregate in these families. In this article, we describe results for simple phobia from 14 of these families (including 129 subjects of whom 57 are affected). A total of 422 markers were genotyped. Multipoint lod score analyses (fully parametric and simple parametric models) and nonparametric analyses were completed using ALLEGRO. We observed significant linkage of simple phobia to chromosome 14 markers. The highest lod score under a fully parametric model was 3.17, at marker D14S75, under a dominant model. Under a fully parametric recessive model, the maximum lod score, also at D14S75, was 2.86. Analysis under a simple parametric model resulted in lod scores of 3.70 (dominant model) or 3.30 (recessive model). The highest Zlr score observed was 3.93 (P=4.1×10−5). The Zlr score was >1 for an extensive region, >77 cM. In all, 12 of the 14 families studied provided positive or zero lod scores at marker D14S75 (dominant model). The homologous genomic region has been implicated by studies mapping quantitative trait loci for a mouse model of fear. The linkage peak may be regarded as highly promising, owing to the breadth of the peak, the convergence of results under different models of inheritance and different analysis methods, and the support from an animal model. This is the first genome scan linkage study for simple phobia, a common disorder that causes high morbidity in the US population.
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Acknowledgements
G Kay and A Lacobelle provided excellent technical assistance. S Goodson, MD, assisted with diagnoses. This work was supported in part by funds from the U.S. Department of Veterans Affairs (the VA Medical Research Program, and the VA Connecticut–Massachusetts Mental Illness Research, Education and Clinical Center (MIRECC)), NIMH Grant K02-MH01387, and NIDA grants DA12849 and DA12690. Some homology data for this paper were retrieved from the Mouse Genome Database (MGD), Mouse Genome Informatics, The Jackson Laboratory, Bar Harbor, Maine (URL: http://www.informatics.jax.org/). (March 2001). Cell lines for many of the samples studied were initially established in the laboratory of Dr K Kidd. Some results of this paper were obtained by using the program package S.A.G.E., which is supported by a U.S. Public Health Service Resource Grant (1 P41 RR03655). Finally, we wish to thank the families who participated in this research.
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Gelernter, J., Page, G., Bonvicini, K. et al. A chromosome 14 risk locus for simple phobia: results from a genomewide linkage scan. Mol Psychiatry 8, 71–82 (2003). https://doi.org/10.1038/sj.mp.4001224
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DOI: https://doi.org/10.1038/sj.mp.4001224
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