{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,4]],"date-time":"2025-10-04T12:27:34Z","timestamp":1759580854202,"version":"3.37.3"},"reference-count":23,"publisher":"Oxford University Press (OUP)","issue":"20","license":[{"start":{"date-parts":[[2021,5,12]],"date-time":"2021-05-12T00:00:00Z","timestamp":1620777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["BE 3828\/3-3"],"award-info":[{"award-number":["BE 3828\/3-3"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>Multiple independently associated SNPs within a linkage disequilibrium region are a common phenomenon. Conditional analysis has been successful in identifying secondary signals. While conditional association tests are limited to specific genomic regions, they are benchmarked with genome-wide scale criterion, a conservative strategy. Within the weighted hypothesis testing framework, we developed a \u2018quasi-adaptive\u2019 method that uses the pairwise correlation (r2) and physical distance (d) from the index association to construct priority functions G =G(r2, d), which assign an SNP-specific \u03b1-threshold to each SNP. Family-wise error rate (FWER) and power of the approach were evaluated via simulations based on real GWAS data. We compared a series of different G-functions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Simulations under the null hypothesis on 1,100 primary SNPs confirmed appropriate empirical FWER for all G-functions. A G-function with optimal r2 = 0.3 between index and secondary SNP which down-weighted SNPs at higher distance step-wise-strong and gave more emphasis on d than on r2 had overall best power. It also gave the best results in application to the real datasets. As a proof of concept, \u2018quasi-adaptive\u2019 method was applied to GWAS on free thyroxine (FT4), inflammatory bowel disease (IBD) and human height. Application of the algorithm revealed 5 secondary signals in our example GWAS on FT4, 5 secondary signals in case of the IBD and 19 secondary signals on human height, that would have gone undetected with the established genome-wide threshold (\u03b1=5\u00d710\u22128).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>https:\/\/github.com\/sghasemi64\/Secondary-Signal.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Supplementary information<\/jats:title>\n                  <jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab332","type":"journal-article","created":{"date-parts":[[2021,4,28]],"date-time":"2021-04-28T16:34:07Z","timestamp":1619627647000},"page":"3521-3529","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of significance of conditionally independent GWAS signals"],"prefix":"10.1093","volume":"37","author":[{"given":"Sahar","family":"Ghasemi","sequence":"first","affiliation":[{"name":"Institute for Community Medicine, University Medicine Greifswald , Greifswald 17475, Germany"},{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald , Greifswald 17475, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Greifswald , Greifswald 17475, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-094X","authenticated-orcid":false,"given":"Alexander","family":"Teumer","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine, University Medicine Greifswald , Greifswald 17475, Germany"},{"name":"DZHK (German Center for Cardiovascular Research), Partner Site Greifswald , Greifswald 17475, Germany"}]},{"given":"Matthias","family":"Wuttke","sequence":"additional","affiliation":[{"name":"Institute of Genetic Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg 79106, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6573-1109","authenticated-orcid":false,"given":"Tim","family":"Becker","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine, University Medicine Greifswald , Greifswald 17475, Germany"},{"name":"3xValue GmbH , Ratingen 47887, Germany"}]}],"member":"286","published-online":{"date-parts":[[2021,5,12]]},"reference":[{"key":"2023051609042377000_btab332-B1","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/ejhg.2009.7","article-title":"Joint analysis of tightly linked SNPs in screening step of genome-wide association studies leads to increased power","volume":"17","author":"Becker","year":"2009","journal-title":"Eur. 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