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Cheung VG, Spielman RS, Ewens KG, Weber TM, Morley M, Burdick JT. Mapping determinants of human gene expression by regional and genome-wide association. Nature . 2005 Oct 27 ; 437(7063):1365-9. PubMed Abstract

Comments on Paper and Primary News
Primary News: Charting Genetic Diversity—First Haplotype Map Appears

Comment by:  John Hardy
Submitted 1 November 2005 Posted 1 November 2005

With the completion of the HapMap and its commercialization by Illumina and Affymetrix, it should be possible for researchers to find susceptibility alleles which have an odds ratio of >2 for any disorder, including Alzheimer disease, over the next couple of years. The expense will be high: Sample sizes of about 500 cases and 500 controls will be needed, and the cost per sample is on the order of $900. But if there are anymore genes with the effect size of ApoE out there, for AD or other diseases, we should now be able to find them.

View all comments by John Hardy

Primary News: Charting Genetic Diversity—First Haplotype Map Appears

Comment by:  Lars Bertram
Submitted 4 November 2005 Posted 4 November 2005

Q&A with Lars Bertram, who is developing the SchizophreniaGene database.

Q: Does the map provide enough resolution?
A: On average, the haplotype map has investigated about 1 SNP every 5,000 bases (i.e., 5 kb). For most applications this density should be sufficient to allow linkage disequilibrium mapping of common variants with at least moderate effects in genetically complex diseases. However, a phase 2 of the HapMap is planned which will probably more than quadruple this resolution.

Q: Will the HapMap help in complex diseases, where several variants on different chromosomes must interact, for example?
A: While the HapMap has many valuable uses in designing and interpreting future genetic association in AD and other diseases, it will unfortunately not help to better understand interactions between different genetic loci or non-genetic factors, because such interactions likely vary from phenotype to phenotype.

Q: Will the HapMap help in...  Read more

View all comments by Lars Bertram

Primary News: Charting Genetic Diversity—First Haplotype Map Appears

Comment by:  Stephen J. Glatt
Submitted 13 November 2005 Posted 13 November 2005

The completion of the HapMap is a major advance for science, and one which will particularly benefit the field of psychiatry. Schizophrenia research has been hampered by a failure to replicate genetic linkage and association studies, and this may in part owe to population differences in allele frequency, haplotype structure, and the inability to select the proper genes and polymorphisms for analysis. The HapMap reduces the "search space" for genetic markers that will show associations with complex diseases, like schizophrenia, across samples, and will thus facilitate the causal polymorphisms that may be shared across these populations. The completion of the first phase of the HapMap is not just important as a milestone marking progress in mapping the human genome, but also it is important for the enhanced level of scientific inquiry it can enable.

View all comments by Stephen J. Glatt

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