Does haplotype diversity predict power for association mapping of disease susceptibility?

Human Genetics
Weihua ZhangNewton E Morton

Abstract

Many recent studies have established that haplotype diversity in a small region may not be greatly diminished when the number of markers is reduced to a smaller set of "haplotype-tagging" single-nucleotide polymorphisms (SNPs) that identify the most common haplotypes. These studies are motivated by the assumption that retention of haplotype diversity assures retention of power for mapping disease susceptibility by allelic association. Using two bodies of real data, three proposed measures of diversity, and regression-based methods for association mapping, we found no scenario for which this assumption was tenable. We compared the chi-square for composite likelihood and the maximum chi-square for single SNPs in diplotypes, excluding the marker designated as causal. All haplotype-tagging methods conserve haplotype diversity by selecting common SNPs. When the causal marker has a range of allele frequencies as in real data, chi-square decreases faster than under random selection as the haplotype-tagging set diminishes. Selecting SNPs by maximizing haplotype diversity is inefficient when their frequency is much different from the unknown frequency of the causal variant. Loss of power is minimized when the difference between minor al...Continue Reading

Citations

Feb 16, 2006·Journal of Human Genetics·Newton E Morton
Oct 9, 2008·Molecular Biotechnology·Andrew Collins
Dec 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Weihua ZhangNewton E Morton
Apr 7, 2005·Human Heredity·Bjarni V HalldórssonFrancisco M De La Vega
Apr 15, 2008·Human Heredity·William TapperAndrew Collins
Jun 3, 2005·The Journal of Clinical Investigation·Newton E Morton
Apr 9, 2005·Human Genomics·Jane GibsonAndrew Collins
Nov 11, 2005·Breast Cancer Research : BCR·Julian Little, Jacques Simard
Feb 6, 2009·PLoS Medicine·Julian LittleUNKNOWN STrengthening the REporting of Genetic Association Studies
Mar 25, 2008·Therapeutics and Clinical Risk Management·Pedro Viana Baptista
Oct 20, 2012·Genetics and Molecular Research : GMR·L ZhangQ Zhu
Feb 4, 2009·European Journal of Epidemiology·Julian LittleNick Birkett
Aug 30, 2008·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·Z R ZhangQ Zhu
Mar 21, 2009·European Journal of Clinical Investigation·Julian LittleNick Birkett
Oct 16, 2010·Journal of Thrombosis and Haemostasis : JTH·U Nowak-GöttlM Stoll
Dec 13, 2006·American Journal of Human Genetics·Newton MortonAndrew Collins
Sep 16, 2004·Human Molecular Genetics·Xiayi KeLon R Cardon
Feb 25, 2005·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Julian LittleMarta Gwinn
Mar 25, 2008·Therapeutics and Clinical Risk Management·Garry Walsh
Sep 7, 2018·Immunogenetics·Lin ZhangJiaqiang Wu
Dec 31, 2015·Genetics·Daniel A SkellyEric A Stone
Nov 16, 2004·Genetic Epidemiology·Daniel J Schaid

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