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Although host genetics appear to play a role, no genetic association study has yet been performed to evaluate this question. In order to investigate if maternal genetic variation is associated with Congenital Zika Syndrome (<jats:styled-content style=\"fixed-case\">CZS<\/jats:styled-content>), we conducted a case\u2013control study in a cohort of Brazilian women infected with <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content> during pregnancy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 100 women who reported symptoms of zika during pregnancy were enrolled and tested for <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content>. Among 52 women positive for <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content> infection, 28 were classified as cases and 24 as controls based on the presence or absence of <jats:styled-content style=\"fixed-case\">CZS<\/jats:styled-content> in their infants. Variations in the coding region of 205 candidate genes involved in cAMP signaling or immune response were assessed by high throughput sequencing and tested for association with development of <jats:styled-content style=\"fixed-case\">CZS<\/jats:styled-content>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>From the 817 single nucleotide variations (<jats:styled-content style=\"fixed-case\">SNV<\/jats:styled-content>s) included in association analyses, 22 <jats:styled-content style=\"fixed-case\">SNV<\/jats:styled-content>s in 17 genes were associated with <jats:styled-content style=\"fixed-case\">CZS<\/jats:styled-content> under an additive model (alpha\u00a0=\u00a00.05). Variations c.319T&gt;C (rs11676272) and c.1297G&gt;A, located at <jats:italic><jats:styled-content style=\"fixed-case\">ADCY<\/jats:styled-content>3<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">ADCY<\/jats:styled-content>7<\/jats:italic> genes showed the most prominent effect. The association of <jats:italic><jats:styled-content style=\"fixed-case\">ADCY<\/jats:styled-content>3<\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">ADCY<\/jats:styled-content>7<\/jats:italic> genes was confirmed using a Sequence Kernel Association Test to assess the joint effect of common and rare variations, and results were statistically significant after adjustment for multiple comparisons (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results suggest that maternal <jats:italic>ADCY<\/jats:italic> genes contribute to <jats:styled-content style=\"fixed-case\">ZIKV<\/jats:styled-content> pathogenicity and influence the outcome of <jats:styled-content style=\"fixed-case\">CZS<\/jats:styled-content>, being promising candidates for further replication studies and functional analysis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/joim.12829","type":"journal-article","created":{"date-parts":[[2018,9,17]],"date-time":"2018-09-17T14:03:14Z","timestamp":1537192994000},"page":"215-222","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Variations in maternal adenylate cyclase genes are associated with congenital Zika syndrome in a cohort from Northeast, Brazil"],"prefix":"10.1111","volume":"285","author":[{"given":"\u00c1. D.","family":"Rossi","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Virologia Molecular Instituto de Biologia Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. R.","family":"Faucz","sequence":"additional","affiliation":[{"name":"Section\u00a0on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Melo","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ)  Campina Grande Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"Pezzuto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia Molecular Instituto de Biologia Universidade Federal do Rio de Janeiro Rio de Janeiro Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. S.","family":"de Azevedo","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ)  Campina Grande Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B. L. F.","family":"Schamber\u2010Reis","sequence":"additional","affiliation":[{"name":"Faculdade de Ci\u00eancias M\u00e9dicas de Campina Grande N\u00facleo de Gen\u00e9tica M\u00e9dica Centro Universit\u00e1rio UniFacisa Campina Grande Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. S.","family":"Tavares","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ)  Campina Grande Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. J.","family":"Mattapallil","sequence":"additional","affiliation":[{"name":"Department of Microbiology &amp; Immunology F. 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