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      Testing for association with multiple traits in generalized estimation equations, with application to neuroimaging data.

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          Abstract

          There is an increasing need to develop and apply powerful statistical tests to detect multiple traits-single locus associations, as arising from neuroimaging genetics and other studies. For example, in the Alzheimer's Disease Neuroimaging Initiative (ADNI), in addition to genome-wide single nucleotide polymorphisms (SNPs), thousands of neuroimaging and neuropsychological phenotypes as intermediate phenotypes for Alzheimer's disease, have been collected. Although some classic methods like MANOVA and newly proposed methods may be applied, they have their own limitations. For example, MANOVA cannot be applied to binary and other discrete traits. In addition, the relationships among these methods are not well understood. Importantly, since these tests are not data adaptive, depending on the unknown association patterns among multiple traits and between multiple traits and a locus, these tests may or may not be powerful. In this paper we propose a class of data-adaptive weights and the corresponding weighted tests in the general framework of generalized estimation equations (GEE). A highly adaptive test is proposed to select the most powerful one from this class of the weighted tests so that it can maintain high power across a wide range of situations. Our proposed tests are applicable to various types of traits with or without covariates. Importantly, we also analytically show relationships among some existing and our proposed tests, indicating that many existing tests are special cases of our proposed tests. Extensive simulation studies were conducted to compare and contrast the power properties of various existing and our new methods. Finally, we applied the methods to an ADNI dataset to illustrate the performance of the methods. We conclude with the recommendation for the use of the GEE-based Score test and our proposed adaptive test for their high and complementary performance.

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          Author and article information

          Journal
          Neuroimage
          NeuroImage
          Elsevier BV
          1095-9572
          1053-8119
          Aug 01 2014
          : 96
          Affiliations
          [1 ] Division of Biostatistics, School of Public Health, Minneapolis, MN 55455, USA.
          [2 ] School of Statistics, University of Minnesota, Minneapolis, MN 55455, USA.
          [3 ] Division of Biostatistics, School of Public Health, Minneapolis, MN 55455, USA. Electronic address: weip@biostat.umn.edu.
          Article
          S1053-8119(14)00222-5 NIHMS581299
          10.1016/j.neuroimage.2014.03.061
          4043944
          24704269

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