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

American Journal of Human Genetics
Itsik Pe'erDavid Altshuler

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 ha...Continue Reading

References

Sep 13, 1996·Science·N Risch, K Merikangas
May 10, 2000·Neurology·S B BressmanN J Risch
Feb 22, 2001·Science·J C VenterX Zhu
Mar 10, 2001·Nature·E S LanderUNKNOWN International Human Genome Sequencing Consortium
Mar 10, 2001·Nature·R SachidanandamUNKNOWN International SNP Map Working Group
Apr 20, 2001·Proceedings of the National Academy of Sciences of the United States of America·N E MortonA Collins
May 11, 2001·Nature·D E ReichE S Lander
Jun 19, 2001·American Journal of Human Genetics·J K Pritchard, M Przeworski
Aug 30, 2001·Trends in Genetics : TIG·D E Reich, E S Lander
Oct 5, 2001·Nature Genetics·M J DalyE S Lander
Oct 5, 2001·Nature Genetics·G C JohnsonJ A Todd
Apr 23, 2002·Nature Reviews. Genetics·Kristin G ArdlieMark Seielstad
Apr 26, 2002·Genetics·Chiara Sabatti, Neil Risch
May 25, 2002·Science·Stacey B GabrielDavid Altshuler
Sep 28, 2002·Human Molecular Genetics·Jonathan K Pritchard, Nancy J Cox
Dec 21, 2002·Science·Noah A RosenbergMarcus W Feldman
Mar 26, 2003·Nature Genetics·David E ReichDavid Altshuler
Apr 12, 2003·Theoretical Population Biology·Rasmus Nielsen, James Signorovitch
Jul 5, 2003·American Journal of Human Genetics·Tara C MatiseArthur L Holden
Dec 20, 2003·Nature·UNKNOWN International HapMap Consortium
Jan 22, 2004·Human Molecular Genetics·Xiayi KePanos Deloukas
May 22, 2004·Nature Reviews. Genetics·UNKNOWN International HapMap Consortium
May 28, 2004·Nature·Christopher S CarlsonDeborah A Nickerson
Aug 7, 2004·Bioinformatics·J C BarrettM J Daly
Dec 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Weihua ZhangNewton E Morton
Feb 18, 2005·Nature Reviews. Genetics·Joel N Hirschhorn, Mark J Daly
Feb 18, 2005·Nature Reviews. Genetics·William Y S WangJohn A Todd
Oct 26, 2005·Nature Genetics·Paul I W de BakkerDavid Altshuler
Oct 29, 2005·Nature·UNKNOWN International HapMap Consortium
Jul 21, 2006·The Journal of Physical Chemistry. B·Janos SzanyiCharles H F Peden

❮ Previous
Next ❯

Citations

Sep 3, 2010·Nature·UNKNOWN International HapMap 3 ConsortiumJean E McEwen
Oct 19, 2006·Nature Reviews. Genetics·Eric Jorgenson, John S Witte
Jun 29, 2006·European Journal of Human Genetics : EJHG·Steven WiltshireMark J Daly
Jun 15, 2007·European Journal of Human Genetics : EJHG·Zongli XuJack A Taylor
Dec 19, 2008·Molecular Biology and Evolution·Sridhar KudaravalliJonathan K Pritchard
Mar 14, 2007·Genome Research·Albert TenesaPeter M Visscher
Dec 21, 2007·Annals of Human Genetics·D C Hamilton, D E C Cole
Aug 29, 2007·PLoS Genetics·Cathy C LaurieMichael W Nachman
Aug 16, 2011·Genetics·Olivier C Martin, Frédéric Hospital
Aug 4, 2007·Genome Research·Bo Eskerod MadsenCarsten Wiuf
Sep 25, 2008·Genetic Epidemiology·Yik Y TeoTaane G Clark
Sep 4, 2007·Journal of Thrombosis and Haemostasis : JTH·M J RiederA E Rettie
Aug 5, 2015·Evolutionary Applications·Diane LeforestierAntoine Branca
Apr 22, 2008·American Journal of Human Genetics·Bret A PayseurJames L Weber
Feb 20, 2008·Nature Reviews. Genetics·Leonid Kruglyak

❮ Previous
Next ❯

Related Concepts

Related Feeds

Barrett Esophagus

Barrett’s esophagus if a serious complication of gastroesophageal reflux disease during which the normal esophageal lining changes to tissue that resembles intestinal lining. Here is the latest research.