CERAMIC: Case-Control Association Testing in Samples with Related Individuals, Based on Retrospective Mixed Model Analysis with Adjustment for Covariates

PLoS Genetics
Sheng ZhongMary Sara McPeek


We consider the problem of genetic association testing of a binary trait in a sample that contains related individuals, where we adjust for relevant covariates and allow for missing data. We propose CERAMIC, an estimating equation approach that can be viewed as a hybrid of logistic regression and linear mixed-effects model (LMM) approaches. CERAMIC extends the recently proposed CARAT method to allow samples with related individuals and to incorporate partially missing data. In simulations, we show that CERAMIC outperforms existing LMM and generalized LMM approaches, maintaining high power and correct type 1 error across a wider range of scenarios. CERAMIC results in a particularly large power increase over existing methods when the sample includes related individuals with some missing data (e.g., when some individuals with phenotype and covariate information have missing genotype), because CERAMIC is able to make use of the relationship information to incorporate partially missing data in the analysis while correcting for dependence. Because CERAMIC is based on a retrospective analysis, it is robust to misspecification of the phenotype model, resulting in better control of type 1 error and higher power than that of prospective ...Continue Reading


Oct 31, 2000·Genetic Epidemiology·N M LairdX Xu
Apr 21, 2001·Biometrics·B Devlin, K Roeder
Oct 9, 2001·American Journal of Human Genetics·D L NewmanN J Cox
Aug 21, 2003·American Journal of Human Genetics·Catherine BourgainMary Sara McPeek
Jun 8, 2004·Biometrics·Mary Sara McPeekCarole Ober
Dec 14, 2004·Genetic Epidemiology·Alice S WhittemoreHabibul Ahsan
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium
Aug 2, 2007·American Journal of Human Genetics·Timothy Thornton, Mary Sara McPeek
Apr 4, 2008·Nature·Stephen J Chanock, David J Hunter
Nov 17, 2009·American Journal of Human Genetics·Zuoheng Wang, Mary Sara McPeek
Apr 30, 2010·Journal of the American Statistical Association·Zuoheng Wang, Mary Sara McPeek
Jun 29, 2010·Nature Genetics·Benjamin F VoightUNKNOWN GIANT Consortium
Aug 17, 2010·Gastroenterology·Naga ChalasaniUNKNOWN Nonalcoholic Steatohepatitis Clinical Research Network
Apr 6, 2011·Genetic Epidemiology·Charalampos PapachristouMark Abney
Sep 6, 2011·Nature Methods·Christoph LippertDavid Heckerman
Jun 16, 2012·Journal of Computational Biology : a Journal of Computational Molecular Cell Biology·Mary Sara McPeek
Jun 19, 2012·Nature Genetics·Xiang Zhou, Matthew Stephens
Aug 14, 2012·Nature Genetics·Andrew P MorrisUNKNOWN DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium
May 7, 2013·American Journal of Human Genetics·Johanna Jakobsdottir, Mary Sara McPeek
Feb 11, 2014·Nature Genetics·UNKNOWN DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) ConsortiumAndrew P Morris
Nov 20, 2014·Frontiers in Endocrinology·Setor K KunutsorTanefa A Apekey
Feb 11, 2015·Nature Methods·Omer WeissbrodDavid Heckerman
Apr 22, 2015·American Journal of Human Genetics·Tristan J HayeckAlkes L Price
Feb 3, 2016·American Journal of Human Genetics·Duo JiangMary Sara McPeek

❮ Previous
Next ❯


Jan 4, 2019·Briefings in Functional Genomics·Denis AwanyEmile R Chimusa
Jun 1, 2018·Proceedings of the National Academy of Sciences of the United States of America·Miaoyan WangJoy Bergelson
Jun 12, 2021·Archives of Virology·Annika AntonssonAdele C Green

❮ Previous
Next ❯

Software Mentioned


Related Concepts

Related Feeds

CZI Human Cell Atlas Seed Network

The aim of the Human Cell Atlas (HCA) is to build reference maps of all human cells in order to enhance our understanding of health and disease. The Seed Networks for the HCA project aims to bring together collaborators with different areas of expertise in order to facilitate the development of the HCA. Find the latest research from members of the HCA Seed Networks here.