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Genetic Association Analysis Using Sibship Data: A Multilevel Model Approach

By Zhihang Peng, Hongbing Shen, Yang Zhao, Monica Ter-Minassian, Nancy Diao, Feng Chen, Ying Zhu and Hao Yu

Abstract

Family based association study (FBAS) has the advantages of controlling for population stratification and testing for linkage and association simultaneously. We propose a retrospective multilevel model (rMLM) approach to analyze sibship data by using genotypic information as the dependent variable. Simulated data sets were generated using the simulation of linkage and association (SIMLA) program. We compared rMLM to sib transmission/disequilibrium test (S-TDT), sibling disequilibrium test (SDT), conditional logistic regression (CLR) and generalized estimation equations (GEE) on the measures of power, type I error, estimation bias and standard error. The results indicated that rMLM was a valid test of association in the presence of linkage using sibship data. The advantages of rMLM became more evident when the data contained concordant sibships. Compared to GEE, rMLM had less underestimated odds ratio (OR). Our results support the application of rMLM to detect gene-disease associations using sibship data. However, the risk of increasing type I error rate should be cautioned when there is association without linkage between the disease locus and the genotyped marker

Topics: genetics, computer science, mathematics, epidemiology, public health, genomics
Publisher: 'Public Library of Science (PLoS)'
Year: 2012
DOI identifier: 10.1371/journal.pone.0031134
OAI identifier: oai:dash.harvard.edu:1/8579874
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