Biases and reconciliation in estimates of linkage disequilibrium in the human genome. Export

@article{citeulike:587202, abstract = {Genetic association studies of common disease often rely on linkage disequilibrium (LD) along the human genome and in the population under study. Although understanding the characteristics of this correlation has been the focus of many large-scale surveys (culminating in genomewide haplotype maps), the results of different studies have yielded wide-ranging estimates. Since understanding these differences (and whether they can be reconciled) has important implications for whole-genome association studies, in this article we dissect biases in these estimations that are due to known aspects of study design and analytic methodology. In particular, we document in the empirical data that the long-known complicating effects of allele frequency, marker density, and sample size largely reconcile all large-scale surveys. Two exceptions are an underappraisal of redundancy among single-nucleotide polymorphisms (SNPs) when evaluation is limited to short regions (as in candidate-gene resequencing studies) and an inflation in the extent of LD in HapMap phase I, which is likely due to oversampling of specific haplotypes in the creation of the public SNP map. Understanding these factors can guide the understanding of empirical LD surveys and has implications for genetic association studies.}, address = {Center for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, USA.}, author = {Pe'er, I. and Chretien, Y. R. and de Bakker, P. I. and Barrett, J. C. and Daly, M. J. and Altshuler, D. M.}, citeulike-article-id = {587202}, citeulike-linkout-0 = {http://dx.doi.org/10.1086/502803}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16532390}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16532390}, doi = {10.1086/502803}, issn = {0002-9297}, journal = {Am J Hum Genet}, keywords = {bias, genome, linkage-disequilibrium, methods, primer, review}, month = {April}, number = {4}, pages = {588--603}, posted-at = {2009-01-31 02:10:20}, priority = {2}, title = {Biases and reconciliation in estimates of linkage disequilibrium in the human genome.}, url = {http://dx.doi.org/10.1086/502803}, volume = {78}, year = {2006} }

TY - JOUR ID - citeulike:587202 L3 - citeulike-article-id:587202 N2 - Genetic association studies of common disease often rely on linkage disequilibrium (LD) along the human genome and in the population under study. Although understanding the characteristics of this correlation has been the focus of many large-scale surveys (culminating in genomewide haplotype maps), the results of different studies have yielded wide-ranging estimates. Since understanding these differences (and whether they can be reconciled) has important implications for whole-genome association studies, in this article we dissect biases in these estimations that are due to known aspects of study design and analytic methodology. In particular, we document in the empirical data that the long-known complicating effects of allele frequency, marker density, and sample size largely reconcile all large-scale surveys. Two exceptions are an underappraisal of redundancy among single-nucleotide polymorphisms (SNPs) when evaluation is limited to short regions (as in candidate-gene resequencing studies) and an inflation in the extent of LD in HapMap phase I, which is likely due to oversampling of specific haplotypes in the creation of the public SNP map. Understanding these factors can guide the understanding of empirical LD surveys and has implications for genetic association studies. IS - 4 JF - Am J Hum Genet SN - 0002-9297 AD - Center for Human Genetic Research, Massachusetts General Hospital, Boston, 02114, USA. EP - 603 TI - Biases and reconciliation in estimates of linkage disequilibrium in the human genome. VL - 78 SP - 588 KW - bias KW - genome KW - linkage-disequilibrium KW - methods KW - primer KW - review AU - Pe'er, I AU - Chretien, YR AU - de Bakker, PI AU - Barrett, JC AU - Daly, MJ AU - Altshuler, DM PY - 2006/04// UR - http://dx.doi.org/10.1086/502803 ER -