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Haplotype-based methods have the advantage of being able to account for correlations between neighbouring SNPs, yet assuming Hardy-Weinberg equilibrium (<jats:italic>HWE<\/jats:italic>) and potentially large number degrees of freedom can harm its statistical power and robustness. Approaches based on principal component analysis (<jats:italic>PCA<\/jats:italic>) are preferable in this regard but their performance varies with methods of extracting principal components (<jats:italic>PC<\/jats:italic> s).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>\n              <jats:italic>PCA<\/jats:italic>-based bootstrap confidence interval test (<jats:italic>PCA-BCIT<\/jats:italic>), which directly uses the <jats:italic>PC<\/jats:italic> scores to assess gene-disease association, was developed and evaluated for three ways of extracting <jats:italic>PC<\/jats:italic> s, i.e., cases only(<jats:italic>CAES<\/jats:italic>), controls only(<jats:italic>COES<\/jats:italic>) and cases and controls combined(<jats:italic>CES<\/jats:italic>). Extraction of <jats:italic>PC<\/jats:italic> s with <jats:italic>COES<\/jats:italic> is preferred to that with <jats:italic>CAES<\/jats:italic> and <jats:italic>CES<\/jats:italic>. Performance of the test was examined via simulations as well as analyses on data of rheumatoid arthritis and heroin addiction, which maintains nominal level under null hypothesis and showed comparable performance with permutation test.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n              <jats:italic>PCA-BCIT<\/jats:italic> is a valid and powerful method for assessing gene-disease association involving multiple SNPs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2156-11-6","type":"journal-article","created":{"date-parts":[[2010,1,26]],"date-time":"2010-01-26T07:17:02Z","timestamp":1264490222000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["PCA-based bootstrap confidence interval tests for gene-disease association involving multiple SNPs"],"prefix":"10.1186","volume":"11","author":[{"given":"Qianqian","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinghua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuzhong","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2010,1,26]]},"reference":[{"key":"753_CR1","doi-asserted-by":"publisher","first-page":"11389","DOI":"10.1073\/pnas.95.19.11389","volume":"95","author":"NE Morton","year":"1998","unstructured":"Morton NE, Collins A: Tests and estimates of allelic association in comples. 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