English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Haplotype misclassification from genotype error and statistical reconstruction and its impact on association estimates

Lamina, C., Küchenhoff, H., Chang-Claude, J., Paulweber, B., Wichmann, H.-E., Illig, T., et al. (2010). Haplotype misclassification from genotype error and statistical reconstruction and its impact on association estimates. Annals of Human Genetics, 74(5), 452-462. doi:10.1111/j.1469-1809.2010.00593.x.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7A67-9 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-7A68-7
Genre: Journal Article

Files

show Files
hide Files
:
Lamina.pdf (Any fulltext), 192KB
Name:
Lamina.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
eDoc_access: PUBLIC
License:
-

Locators

show

Creators

show
hide
 Creators:
Lamina, Claudia, Author
Küchenhoff, Helmut, Author
Chang-Claude, Jenny, Author
Paulweber, Bernhard, Author
Wichmann, H.-Erich, Author
Illig, Thomas, Author
Hoehe, Margret R.1, Author              
Kronenberg, Florian, Author
Heid, Iris M., Author
Affiliations:
1Genetic Variation, Haplotypes, and Genetics of Complex Disease (Margret Hoehe), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479651              

Content

show
hide
Free keywords: Haplotypes; measurement error; genotyping error; association studies; misclassification
 Abstract: Haplotypes are an important concept for genetic association studies, but involve uncertainty due to statistical reconstruction from single nucleotide polymorphism (SNP) genotypes and genotype error. We developed a re-sampling approach to quantify haplotype misclassification probabilities and implemented the MC-SIMEX approach to tackle this as a 3 × 3 misclassification problem. Using a previously published approach as a benchmark for comparison, we evaluated the performance of our approach by simulations and exemplified it on real data from 15 SNPs of the APM1 gene. Misclassification due to reconstruction error was small for most, but notable for some, especially rarer haplotypes. Genotype error added misclassification to all haplotypes resulting in a non-negligible drop in sensitivity. In our real data example, the bias of association estimates due to reconstruction error alone reached −48.2% for a 1% genotype error, indicating that haplotype misclassification should not be ignored if high genotype error can be expected. Our 3 × 3 misclassification view of haplotype error adds a novel perspective to currently used methods based on genotype intensities and expected number of haplotype copies. Our findings give a sense of the impact of haplotype error under realistic scenarios and underscore the importance of high-quality genotyping, in which case the bias in haplotype association estimates is negligible.

Details

show
hide
Language(s): eng - English
 Dates: 2010-09
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: eDoc: 556533
DOI: 10.1111/j.1469-1809.2010.00593.x
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Annals of Human Genetics
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 74 (5) Sequence Number: - Start / End Page: 452 - 462 Identifier: ISSN: 1469-1809