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Altered Wnt\u2010signaling has been linked with several neurodevelopmental disorders including attention\u2010deficit\/hyperactivity disorder (ADHD) as well as with cognitive functions, learning and memory. Particularly, lipoprotein receptor\u2010related protein 5 (LRP5) or LRP6 coreceptors, responsible in the activation of the canonical Wnt\u2010pathway, were associated with cognitive alterations in psychiatric disorders. Following the hypothesis of Wnt involvement in ADHD, we investigated the association of genetic variations in LRP5<\/jats:italic> and LRP6<\/jats:italic> genes with three independent child and adolescent ADHD (cADHD) samples (total 2,917 participants), followed by a meta\u2010analysis including previously published data. As ADHD is more prevalent in males, we stratified the analysis according to sex and compared the results with the recent ADHD Psychiatric Genomic Consortium (PGC) GWAS. Meta\u2010analyzing our data including previously published cADHD studies, association of LRP5<\/jats:italic> intronic rs4988319 and rs3736228 (Ala1330Val) with cADHD was observed among girls (OR\u2009=\u20091.80 with 95% CI\u2009=\u20091.07\u20133.02, p<\/jats:italic>\u2009=\u2009.0259; and OR\u2009=\u20092.08 with 95% CI\u2009=\u20091.01\u20134.46, p<\/jats:italic>\u2009=\u2009.0026, respectively), whereas in boys association between LRP6<\/jats:italic> rs2302685 (Val1062Ile) and cADHD was present (OR\u2009=\u20091.66, CI\u2009=\u20091.20\u20132.31, p<\/jats:italic>\u2009=\u2009.0024). In the PGC\u2010ADHD dataset (using pooled data of cADHD and adults) tendency of associations were observed only among females with OR\u2009=\u20091.09 (1.02\u20131.17) for LRP5<\/jats:italic> rs3736228 and OR\u2009=\u20091.18 (1.09\u20131.25) for LRP6<\/jats:italic> rs2302685. Together, our findings suggest a potential sex\u2010specific link of cADHD with LRP5<\/jats:italic> and LRP6<\/jats:italic> gene variants, which could contribute to the differences in brain maturation alterations in ADHD affected boys and girls, and suggest possible therapy targets.<\/jats:p>","DOI":"10.1002\/ajmg.b.32695","type":"journal-article","created":{"date-parts":[[2018,11,26]],"date-time":"2018-11-26T04:44:06Z","timestamp":1543207446000},"page":"365-376","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["The involvement of the canonical Wnt\u2010signaling receptor LRP5<\/i> and LRP6<\/i> gene variants with ADHD and sexual dimorphism: Association study and meta\u2010analysis"],"prefix":"10.1002","volume":"180","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8505-7265","authenticated-orcid":false,"given":"Edna","family":"Gr\u00fcnblatt","sequence":"first","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychotherapy University Hospital of Psychiatry Zurich, University of Zurich Zurich Switzerland"},{"name":"Neuroscience Center Zurich University of Zurich and ETH Zurich Zurich Switzerland"},{"name":"Zurich Center for Integrative Human Physiology University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsofia","family":"Nemoda","sequence":"additional","affiliation":[{"name":"Institute of Medical Chemistry Molecular Biology and Pathobiochemistry, Semmelweis University Budapest Hungary"},{"name":"Molecular Psychiatry Research Group MTA\u2010SE NAP\u2010B, Hungarian Academy of Sciences Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna Maria","family":"Werling","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychotherapy University Hospital of Psychiatry Zurich, University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Roth","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychotherapy University Hospital of Psychiatry Zurich, University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nora","family":"Angyal","sequence":"additional","affiliation":[{"name":"Institute of Medical Chemistry Molecular Biology and Pathobiochemistry, Semmelweis University Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsanett","family":"Tarnok","sequence":"additional","affiliation":[{"name":"Vadaskert Child and Adolescent Psychiatric Hospital Budapest Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hauke","family":"Thomsen","sequence":"additional","affiliation":[{"name":"Division of Molecular Genetic Epidemiology (C050) German Cancer Research Center (DKFZ) Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Triinu","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy, University of Duisburg\u2010Essen, University Hospital Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Hinney","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy, University of Duisburg\u2010Essen, University Hospital Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Hebebrand","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry Psychosomatics and Psychotherapy, University of Duisburg\u2010Essen, University Hospital Essen Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus\u2010Peter","family":"Lesch","sequence":"additional","affiliation":[{"name":"Division of Molecular Psychiatry Center of Mental Health, University of Wuezburg Wuerzburg Germany"},{"name":"Laboratory of Psychiatric Neurobiology Institute of Molecular Medicine, I. 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