Candidate genes in psychiatry: an epidemiological perspective.

Interest in candidate genes in psychiatry has been revived by the success of that approach in Alzheimer's disease as well as by discouragement over the results to date of searches for linkage. If mutations in candidate genes could be detected directly many of the complexities of searching for them indirectly through linkage could be avoided. As attractive as this approach may sound, mutation searches with candidate genes will introduce a new set of difficulties: the large number and low a priori probability of potential candidate genes virtually guarantees that most positive findings will be false positives. Consequently, if candidate genes are to be systematically studied, procedures need to be established for minimizing and efficiently disconfirming false positive results.

[1]  M. Murphy.  The molecular pathogenesis of Alzheimer's disease: clinical prospects , 1992, The Lancet.

[2]  C. Bonaïti‐pellié,et al.  Strategies based on marker information for the study of human diseases , 1992, Annals of human genetics.

[3]  J. Hardy,et al.  Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene , 1991, Nature.

[4]  P. Easterbrook,et al.  Publication bias in clinical research , 1991, The Lancet.

[5]  M. Pericak-Vance,et al.  Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease , 1991, Nature.

[6]  P. McGuffin,et al.  Exclusion of a schizophrenia susceptibility gene from the chromosome 5q11-q13 region: new data and a reanalysis of previous reports. , 1990, American journal of human genetics.

[7]  L. Kupper,et al.  Effective testing of gene-disease associations. , 1990, American journal of human genetics.

[8]  K. Kidd,et al.  Re-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish , 1989, Nature.

[9]  T. Sekiya,et al.  Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[10]  R. Gibbs,et al.  Identification of mutations leading to the Lesch-Nyhan syndrome by automated direct DNA sequencing of in vitro amplified cDNA. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[11]  K. Lange,et al.  The affected-pedigree-member method of linkage analysis. , 1988, American journal of human genetics.

[12]  C. Falk,et al.  Haplotype relative risks: an easy reliable way to construct a proper control sample for risk calculations , 1987, Annals of human genetics.

[13]  L. Heston,et al.  Delineation of genetic predisposition to multifactorial disease: a general approach on the threshold of feasibility. , 1992, Genomics.

[14]  N. Risch,et al.  Genetic linkage and complex diseases, with special reference to psychiatric disorders , 1990, Genetic epidemiology.

[15]  V. Sheffield,et al.  Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[16]  J. Sutcliffe,et al.  mRNA in the mammalian central nervous system. , 1988, Annual review of neuroscience.

[17]  I. Borecki,et al.  Power of the affected‐sib‐pair method for heterogeneous disorders , 1988, Genetic epidemiology.