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An adaptive gene-level association test for pedigree data.


ABSTRACT: BACKGROUND:We propose a gene-level association test that accounts for individual relatedness and population structures in pedigree data in the framework of linear mixed models (LMMs). Our method data-adaptively combines the results across a class of score-based tests, only requiring fitting a single null model (under the null hypothesis) for the whole genome, thereby being computationally efficient. RESULTS:We applied our approach to test for association with the high-density lipoprotein (HDL) ratio of post- and pretreatments in GAW20 data. Using the LMM similar to that used by Aslibekyan et al. (PLos One, 7:48663, 2012), our method identified 2 nearly significant genes (APOA5 and ZNF259) near rs964184, whereas neither the other gene-level tests nor the standard test on each individual single-nucleotide polymorphism (SNP) detected any significant gene in a genome-wide scan. CONCLUSIONS:Gene-level association testing can be a complementary approach to the SNP-level association testing and our method is adaptive and efficient compared to several other existing gene-level association tests.

SUBMITTER: Park JY 

PROVIDER: S-EPMC6157189 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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An adaptive gene-level association test for pedigree data.

Park Jun Young JY   Wu Chong C   Pan Wei W  

BMC genetics 20180917 Suppl 1


<h4>Background</h4>We propose a gene-level association test that accounts for individual relatedness and population structures in pedigree data in the framework of linear mixed models (LMMs). Our method data-adaptively combines the results across a class of score-based tests, only requiring fitting a single null model (under the null hypothesis) for the whole genome, thereby being computationally efficient.<h4>Results</h4>We applied our approach to test for association with the high-density lipo  ...[more]

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