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Methods Mol Biol. 2010;620:541-60. doi: 10.1007/978-1-60761-580-4_21.

Methods for combining multiple genome-wide linkage studies.

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Department of Statistics, Oklahoma State University, OK, Stillwater, USA.


Cardiovascular disease, metabolic syndrome, schizophrenia, diabetes, bipolar disorder, and autism are a few of the numerous complex diseases for which researchers are trying to decipher the genetic composition. One interest of geneticists is to determine the quantitative trait loci (QTLs) that underlie the genetic portion of these diseases and their risk factors. The difficulty for researchers is that the QTLs underlying these diseases are likely to have small to medium effects which will necessitate having large studies in order to have adequate power. Combining information across multiple studies provides a way for researchers to potentially increase power while making the most of existing studies.Here, we will explore some of the methods that are currently being used by geneticists to combine information across multiple genome-wide linkage studies. There are two main types of meta-analyses: (1) those that yield a measure of significance, such as Fisher's p-value method along with its extensions/modifications and the genome search meta-analysis (GSMA) method, and (2) those that yield a measure of a common effect size and the corresponding standard error, such as model-based methods and Bayesian methods. Some of these methods allow for the assessment of heterogeneity. This chapter will conclude with a recommendation for usage.

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