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Standard regression models used in Genome-Wide Association Studies (GWAS) identify loci with a strong effect size, whereas GWAS meta-analyses are often needed to capture weak loci contributing to the missing heritability. Development of novel machine learning algorithms for merging genotype data with other omics data is highly needed as it could enhance the prioritization of weak loci.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We developed cNMTF (corrected non-negative matrix tri-factorization), an integrative algorithm based on clustering techniques of biological data. This method assesses the inter-relatedness between genotypes, phenotypes, the damaging effect of the variants and gene networks in order to identify loci-trait associations. cNMTF was used to prioritize genes associated with lipid traits in two population cohorts. We replicated 129 genes reported in GWAS world-wide and provided evidence that supports 85% of our findings (226 out of 265 genes), including recent associations in literature (NLGN1), regulators of lipid metabolism (DAB1) and pleiotropic genes for lipid traits (CARM1). Moreover, cNMTF performed efficiently against strong population structures by accounting for the individuals\u2019 ancestry. As the method is flexible in the incorporation of diverse omics data sources, it can be easily adapted to the user\u2019s research needs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>An R package (cnmtf) is available at https:\/\/lgl15.github.io\/cnmtf_web\/index.html.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btz310","type":"journal-article","created":{"date-parts":[[2019,4,25]],"date-time":"2019-04-25T19:21:53Z","timestamp":1556220113000},"page":"5182-5190","source":"Crossref","is-referenced-by-count":10,"title":["Identification of disease-associated loci using machine learning for genotype and network data integration"],"prefix":"10.1093","volume":"35","author":[{"given":"Luis G","family":"Leal","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Centre for Integrative Systems Biology and Bioinformatics, Imperial College London , London SW7 2AZ, UK"}]},{"given":"Alessia","family":"David","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Centre for Integrative Systems Biology and Bioinformatics, Imperial College London , London SW7 2AZ, UK"}]},{"given":"Marjo-Riita","family":"Jarvelin","sequence":"additional","affiliation":[{"name":"Center for Life Course Health Research, Faculty of Medicine, University of Oulu , Oulu FI-90014, Finland"},{"name":"Biocenter Oulu, University of Oulu , Oulu 90220, Finland"},{"name":"Unit of Primary Health Care, Oulu University Hospital , Oulu 90220, Finland"},{"name":"Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London , London W2 1PG, UK"},{"name":"Department of Life Sciences, College of Health and Life Sciences, Brunel University London , Middlesex UB8 3PH, UK"}]},{"given":"Sylvain","family":"Sebert","sequence":"additional","affiliation":[{"name":"Center for Life Course Health Research, Faculty of Medicine, University of Oulu , Oulu FI-90014, Finland"},{"name":"Biocenter Oulu, University of Oulu , Oulu 90220, Finland"}]},{"given":"Minna","family":"M\u00e4nnikk\u00f6","sequence":"additional","affiliation":[{"name":"Center for Life Course Health Research, Faculty of Medicine, University of Oulu , Oulu FI-90014, Finland"}]},{"given":"Ville","family":"Karhunen","sequence":"additional","affiliation":[{"name":"Center for Life Course Health Research, Faculty of Medicine, University of Oulu , Oulu FI-90014, Finland"},{"name":"Biocenter Oulu, University of Oulu , Oulu 90220, Finland"},{"name":"Unit of Primary Health Care, Oulu University Hospital , Oulu 90220, Finland"},{"name":"Department of Epidemiology and Biostatistics, MRC-PHE Centre for Environment and Health, School of Public Health, Imperial College London , London W2 1PG, UK"},{"name":"Department of Life Sciences, College of Health and Life Sciences, Brunel University London , Middlesex UB8 3PH, UK"}]},{"given":"Eleanor","family":"Seaby","sequence":"additional","affiliation":[{"name":"Program in Medical and Population Genetics, Broad Institute of MIT and Harvard , Cambridge, MA, USA"}]},{"given":"Clive","family":"Hoggart","sequence":"additional","affiliation":[{"name":"Department of Medicine, Imperial College London , London W2 1PG, UK"}]},{"given":"Michael J E","family":"Sternberg","sequence":"additional","affiliation":[{"name":"Department of Life Sciences, Centre for Integrative Systems Biology and Bioinformatics, Imperial College London , London SW7 2AZ, UK"}]}],"member":"286","published-online":{"date-parts":[[2019,5,9]]},"reference":[{"key":"2023013108380256900_btz310-B1","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1093\/bioinformatics\/btu261","article-title":"EPIQ\u2014efficient detection of SNP-SNP epistatic interactions for quantitative traits","volume":"30","author":"Arkin","year":"2014","journal-title":"Bioinformatics"},{"key":"2023013108380256900_btz310-B2","doi-asserted-by":"crossref","first-page":"16.","DOI":"10.1186\/s13073-015-0138-2","article-title":"Rare variant association studies: considerations, challenges and opportunities","volume":"7","author":"Auer","year":"2015","journal-title":"Genome Med"},{"key":"2023013108380256900_btz310-B3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/ng.269","article-title":"Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts","volume":"41","author":"Aulchenko","year":"2009","journal-title":"Nat. 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