Linkage versus Association Studies
Doctor Anil Malhotra compares (older) linkage and (more modern) association techniques for identifying candidate genes for disorders.
Linkage analysis was a very popular method for detecting genes of major effect particularly in psychiatry. It was used mostly in the '80s and perhaps early 1990s usually based on within-family design either sibling pairs or large multiplex pedigrees. As I said, it is really optimally designed for disorders in which their genes have major effect. One of the things I think that came out of that generation of linkage studies was [that] it is relatively clear that if there are genes of major effect they are relatively rare and relatively isolated populations within schizophrenia. Association studies take the opposite approach. In general, there are case-control association studies, though there are family-based approaches also, which hopefully are going to find genes that have less of a strong effect and thus maybe multiple genes of lesser effect can be detected. With the association approach, where we essentially compare allele frequencies between cases and controls and then examine whatever number of genes or number of polymorphisms in individual study.
linkage, study, analysis, association, allele frequency, case control, polymorphisms, pedigree, genes, schizophrenia, Anil, Malhotra
Doctor Anil Malhotra discusses the search for genes in both bipolar disorder and schizophrenia, both of which are in their infancy.
Doctor Anil Malhotra discusses endophenotype strategies for studying schizophrenia, which can examine neurocognitive function or brain-imaging.
Doctor Anil Malhotra discusses emerging research relating specific genes to positive (DISC1) and negative (e.g. dysbindin) symptoms of schizophrenia.
Doctor Anil Malhotra discusses how transcription factors can turn genes on or off, possibly leading to increased or reduced risk of illness.
Professor Daniel Weinberger discusses research that makes neuregulin a candidate gene for schizophrenia.
Doctor Anil Malhotra discusses new technologies that allow scientists to genotype large numbers of genetic polymorphisms.
Kenneth Kidd talks about frequency of different DNA variations.
Doctor Anil Malhotra discusses the problem of deciding what meets the criteria for statistical significance for microarray studies.
Doctor Anil Malhotra discusses that because whole genome microarray studies examine so much genetic data, the daners of false-positive results are very real.
Doctor Anil Malhotra compares the effectiveness of of second generation antipsychotic medications, such as Clozapine, with earlier medications.