title: A rare variant association test based on combinations of single-variant tests.
abstract: Next generation sequencing technologies make direct testing rare variant associations possible. However, the development of powerful statistical methods for rare variant association studies is still underway. Most of existing methods are burden and quadratic tests. Recent studies show that the performance of each of burden and quadratic tests depends strongly upon the underlying assumption and no test demonstrates consistently acceptable power. Thus, combined tests by combining information from the burden and quadratic tests have been proposed recently. However, results from recent studies (including this study) show that there exist tests that can outperform both burden and quadratic tests. In this article, we propose three classes of tests that include tests outperforming both burden and quadratic tests. Then, we propose the optimal combination of single-variant tests (OCST) by combining information from tests of the three classes. We use extensive simulation studies to compare the performance of OCST with that of burden, quadratic and optimal single-variant tests. Our results show that OCST either is the most powerful test or has similar power with the most powerful test. We also compare the performance of OCST with that of the two existing combined tests. Our results show that OCST has better power than the two combined tests.
authors: Department of Mathematical Sciences, Michigan Technological University, Houghton, Michigan, United States of America.
authors: Qiuying
authors: Q
authors: Sha
authors: Shuanglin
authors: S
authors: Zhang
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics; D000074183:ATPases Associated with Diverse Cellular Activities; D000251:Adenosine Triphosphatases / Q000235:genetics; D024142:Collagen Type VI / Q000235:genetics; D003198:Computer Simulation; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005787:Gene Frequency; D056726:Genetic Association Studies; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D054758:A Kinase Anchor Proteins; C075176:AHNAK protein, human; C085467:AKAP13 protein, human; D024142:Collagen Type VI; D016326:Extracellular Matrix Proteins; C500786:FREM2 protein, human; D008565:Membrane Proteins; D015778:Minor Histocompatibility Antigens; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D000251:Adenosine Triphosphatases; C503949:MDN1 protein, human; D000074183:ATPases Associated with Diverse Cellular Activities
keywords: association study; next generation sequencing; rare variant