Influence of genotyping error in linkage mapping for complex traits--an analytic study

Area of Science:

• Genetics
• Bioinformatics
• Statistical genetics

Background:

• Linkage studies in families remain crucial for disease gene mapping.
• Single-nucleotide-polymorphism (SNP) array technology enhances linkage data but is susceptible to genotyping errors.
• The impact of genotyping errors on selective designs for continuous traits requires further assessment.

Purpose of the Study:

• To analytically quantify the effect of genotyping errors on linkage testing in family studies, specifically using affected sib pair (ASP) designs.
• To assess the influence of genotyping errors on selective designs for continuous traits.
• To propose a method for controlling genotyping errors in linkage analysis.

Main Methods:

• Utilized an identity-by-descent (IBD) regression-based paradigm for linkage testing.
• Analyzed the effects of genotyping error models under specific selection schemes for sibling pairs.
• Developed a genomic control strategy by modifying the regression intercept.

Main Results:

• Genotyping errors decrease power in extremely concordant (EC) designs and increase type I error in extremely discordant (ED) designs.
• The most severe effects of genotyping error were observed in designs with less extreme selection.
• A genomic control modification of the regression intercept was proposed to mitigate genotyping errors.

Conclusions:

• Genotyping errors significantly affect type I error and power in selective linkage designs for continuous traits.
• Designs incorporating both EC and ED sib pairs demonstrate resilience to genotyping errors.
• The proposed genomic control strategy offers a method for more robust inference, particularly with SNP array data.