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Nat Genet DOI:10.1038/ng.2876

Advantages and pitfalls in the application of mixed-model association methods.

Publication TypeJournal Article
Year of Publication2014
AuthorsYang, J, Zaitlen, NA, Goddard, ME, Visscher, PM, Price, AL
JournalNat Genet
Date Published2014 Feb
KeywordsColitis, Ulcerative, Computer Simulation, Genetic Association Studies, Humans, Linear Models, Multiple Sclerosis, Research Design

Mixed linear models are emerging as a method of choice for conducting genetic association studies in humans and other organisms. The advantages of the mixed-linear-model association (MLMA) method include the prevention of false positive associations due to population or relatedness structure and an increase in power obtained through the application of a correction that is specific to this structure. An underappreciated point is that MLMA can also increase power in studies without sample structure by implicitly conditioning on associated loci other than the candidate locus. Numerous variations on the standard MLMA approach have recently been published, with a focus on reducing computational cost. These advances provide researchers applying MLMA methods with many options to choose from, but we caution that MLMA methods are still subject to potential pitfalls. Here we describe and quantify the advantages and pitfalls of MLMA methods as a function of study design and provide recommendations for the application of these methods in practical settings.


Alternate JournalNat. Genet.
PubMed ID24473328
PubMed Central IDPMC3989144
Grant ListP01 GM099568 / GM / NIGMS NIH HHS / United States
R01 GM075091 / GM / NIGMS NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States