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Deciphering the genetic architecture of such traits with traditional quantitative trait locus (QTL) mapping methods is challenging. Here, we investigated the genetic architecture of brain size (and the size of five different brain parts) in nine\u2010spined sticklebacks (<jats:italic>Pungitius pungitius<\/jats:italic>) with the aid of novel multilocus QTL\u2010mapping approaches based on a de\u2010biased LASSO method. Apart from having more statistical power to detect QTL and reduced rate of false positives than conventional QTL\u2010mapping approaches, the developed methods can handle large marker panels and provide estimates of genomic heritability. Single\u2010locus analyses of an F<jats:sub>2<\/jats:sub>interpopulation cross with 239 individuals and 15 198, fully informative single nucleotide polymorphisms (SNPs) uncovered 79 QTL associated with variation in stickleback brain size traits. Many of these loci were in strong linkage disequilibrium (LD) with each other, and consequently, a multilocus mapping of individual SNPs, accounting for LD structure in the data, recovered only four significant QTL. However, a multilocus mapping of SNPs grouped by linkage group (LG) identified 14 LGs (1\u20136 depending on the trait) that influence variation in brain traits. For instance, 17.6% of the variation in relative brain size was explainable by cumulative effects of SNPs distributed over six LGs, whereas 42% of the variation was accounted for by all 21 LGs. Hence, the results suggest that variation in stickleback brain traits is influenced by many small\u2010effect loci. Apart from suggesting moderately heritable (<jats:italic>h<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0\u2248\u00a00.15\u20130.42) multifactorial genetic architecture of brain traits, the results highlight the challenges in identifying the loci contributing to variation in quantitative traits. Nevertheless, the results demonstrate that the novel QTL\u2010mapping approach developed here has distinctive advantages over the traditional QTL\u2010mapping methods in analyses of dense marker panels.<\/jats:p>","DOI":"10.1111\/mec.14005","type":"journal-article","created":{"date-parts":[[2017,1,4]],"date-time":"2017-01-04T07:32:48Z","timestamp":1483515168000},"page":"1557-1575","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Deciphering the genomic architecture of the stickleback brain with a novel multilocus gene\u2010mapping approach"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8469-7295","authenticated-orcid":false,"given":"Zitong","family":"Li","sequence":"first","affiliation":[{"name":"Ecological Genetics Research Unit Department of Biosciences University of Helsinki P.O. 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