{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:24:09Z","timestamp":1790627049561,"version":"4.1.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,8,31]],"date-time":"2020-08-31T00:00:00Z","timestamp":1598832000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Neurofibromatosis type 1 (NF1) is a tumor\u2010predisposition disorder that arises due to pathogenic variants in tumor suppressor <jats:italic>NF1<\/jats:italic>. NF1 has variable expressivity that may be due, at least in part, from heritable elements such as modifier genes; however, few genetic modifiers have been identified to date.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, we performed a genome\u2010wide association analysis of the number of caf\u00e9\u2010au\u2010lait macules (CALM) that are considered a tumor\u2010like trait as a clinical phenotype modifying NF1.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A borderline genome\u2010wide significant association was identified in the discovery cohort (CALM1, <jats:italic>N<\/jats:italic>\u00a0=\u00a0112) between CALM number and rs12190451 (and rs3799603, <jats:italic>r<\/jats:italic><jats:sup>2<\/jats:sup>\u00a0=\u00a01.0; <jats:italic>p<\/jats:italic>\u00a0=\u00a07.4\u00a0\u00d7\u00a010<jats:sup>\u22128<\/jats:sup>) in the intronic region of <jats:italic>RPS6KA2<\/jats:italic>. Although, this association was not replicated in the second cohort (CALM2, <jats:italic>N<\/jats:italic>\u00a0=\u00a059) and a meta\u2010analysis did not show significantly associated variants in this region, a significant corroboration score (0.72) was obtained for the <jats:italic>RPS6KA2<\/jats:italic> signal in the discovery cohort (CALM1) using Complementary Pairs Stability Selection for Genome\u2010Wide Association Studies (ComPaSS\u2010GWAS) analysis, suggesting that the lack of replication may be due to heterogeneity of the cohorts rather than type I error.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>rs12190451 is located in a melanocyte\u2010specific enhancer and may influence <jats:italic>RPS6KA2<\/jats:italic> expression in melanocytes\u2014warranting further functional studies.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.1400","type":"journal-article","created":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T01:36:38Z","timestamp":1598924198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Genome\u2010wide association study of caf\u00e9\u2010au\u2010lait macule number in neurofibromatosis type 1"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2329-326X","authenticated-orcid":false,"given":"Heejong","family":"Sung","sequence":"first","affiliation":[{"name":"Genometrics Section, Computational and Statistical Genomics Branch National Human Genome Research Institute National Institutes of Health Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula L.","family":"Hyland","sequence":"additional","affiliation":[{"name":"Integrative Tumor Epidemiology Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA"},{"name":"Division of Applied Regulatory Science, Office of Translational Science, Center for Drug Evaluation &amp; Research U.S. Food and Drug Administration Silver Spring MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3893-3685","authenticated-orcid":false,"given":"Alexander","family":"Pemov","sequence":"additional","affiliation":[{"name":"Clinical Genetics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy A.","family":"Sabourin","sequence":"additional","affiliation":[{"name":"Genometrics Section, Computational and Statistical Genomics Branch National Human Genome Research Institute National Institutes of Health Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea M.","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Bass","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kedest","family":"Teshome","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Luo","sequence":"additional","affiliation":[{"name":"Frederick National Laboratory for Cancer Research Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"Frederick National Laboratory for Cancer Research","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte C.","family":"Widemann","sequence":"additional","affiliation":[{"name":"Pediatric Oncology Branch Center for Cancer Research National Cancer Institute National Institutes of Health Bethesda MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8193-1488","authenticated-orcid":false,"given":"Douglas R.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Clinical Genetics Branch Division of Cancer Epidemiology and Genetics National Cancer Institute National Institutes of Health Rockville MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander F.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Genometrics Section, Computational and Statistical Genomics Branch National Human Genome Research Institute National Institutes of Health Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,8,31]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu389"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm2509"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2009.09.042"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(09)70033\u20106"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201009\u20101752"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096\u20108628(19990326)89:1<7:AID\u2010AJMG4>3.0.CO;2\u2010#"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.4137\/grsb.S40768"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2009.358"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000250332.89420.e6"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000327379"},{"issue":"2","key":"e_1_2_9_13_1","first-page":"305","article-title":"An analysis of variation in expression of neurofibromatosis (NF) type 1 (NF1): Evidence for modifying genes","volume":"53","author":"Easton D. 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