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Yet to date, progress in our understanding of genotype\u2013phenotype associations in nonmodel organisms in general and natural vertebrate populations in particular has been hampered by small sample sizes typically available for wildlife populations and a resulting lack of statistical power, as well as a limited ability to control for false\u2010positive signals. Here we propose to combine a genome\u2010wide association study (GWAS)\u00a0and <jats:italic>F<\/jats:italic><jats:sub>ST<\/jats:sub>\u2010based approach with population\u2010level replication to partly overcome these limitations. We present a case study in which we used this approach in combination with genotyping\u2010by\u2010sequencing (GBS)\u00a0single nucleotide polymorphism (SNP) data to identify genomic regions associated with <jats:italic>Borrelia afzelii<\/jats:italic> resistance or susceptibility in the natural rodent host of this Lyme disease\u2010causing spirochete, the bank vole (<jats:italic>Myodes glareolus<\/jats:italic>). Using this combined approach we identified four consensus SNPs located in exonic regions of the genes <jats:italic>Slc26a4<\/jats:italic>, <jats:italic>Tns3<\/jats:italic>, <jats:italic>Wscd1<\/jats:italic> and <jats:italic>Espnl<\/jats:italic>, which were significantly associated with the voles\u2019 <jats:italic>Borrelia<\/jats:italic> infectious status within and across populations. Functional links between host responses to bacterial infections and most of these genes have previously been demonstrated in other rodent systems, making them promising new candidates for the study of evolutionary host responses to <jats:italic>Borrelia<\/jats:italic> emergence. Our approach is applicable to other systems and may facilitate the identification of genetic variants underlying disease resistance or susceptibility, as well as other ecologically relevant traits, in wildlife populations.<\/jats:p>","DOI":"10.1111\/mec.15410","type":"journal-article","created":{"date-parts":[[2020,3,12]],"date-time":"2020-03-12T17:00:05Z","timestamp":1584032405000},"page":"1386-1397","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Combining genome\u2010wide association study and <i>F<\/i><sub>ST<\/sub>\u2010based approaches to identify targets of <i>Borrelia<\/i>\u2010mediated selection in natural rodent hosts"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7188-4048","authenticated-orcid":false,"given":"Luca","family":"Cornetti","sequence":"first","affiliation":[{"name":"Department of Evolutionary Biology and Environmental Studies University of Zurich Zurich Switzerland"},{"name":"Zoological Institute University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4806-4102","authenticated-orcid":false,"given":"Barbara","family":"Tschirren","sequence":"additional","affiliation":[{"name":"Centre for Ecology and Conservation University of Exeter Penryn UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,4,6]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1134\/S0026893309050148"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm732"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2010.1920"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0030626"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm108"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/0471250953.bi1110s43"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/mec.14146"},{"issue":"1","key":"e_1_2_8_9_1","first-page":"1","article-title":"Fitting linear mixed\u2010effects models using lme4","volume":"67","author":"Bates D.","year":"2011","journal-title":"Journal of Statistical Software"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-445"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tree.2009.06.015"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/1755-0998.12669"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.2018.1056"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/447655a"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/mec.14812"},{"key":"e_1_2_8_18_1","unstructured":"Cornetti L. &Tschirren B.(2020a).NCBI Sequence Read Archive (BioProject ID: PRJNA306409 SRA experiment SRR3031372).https:\/\/www.ncbi.nlm.nih.gov\/bioproject\/PRJNA306409"},{"key":"e_1_2_8_19_1","article-title":"Data from: Combining GWAS and F\n                  ST\u2010based approaches to identify targets of Borrelia\u2010mediated selection in natural rodent hosts","author":"Cornetti L.","year":"2020","journal-title":"Dryad"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btr330"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.287.5452.443"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/bfgp\/elq031"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.01078-08"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-45"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12686-011-9548-7"},{"key":"e_1_2_8_26_1","unstructured":"Ersts P. 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