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Multiple risk factors, including host genetics, environmental factor, and EBV infection, have been linked to the development of NPC, particularly in the familial clustering cases. However, the cause of NPC endemicity remains enigmatic due possibly to the complicated interplay between these risk factors. Recently, positive Epstein\u2010Barr virus (EBV) DNA loads at nasopharyngeal (NP) cavity has been found to reflect NPC development and applied in NPC screening. To examine whether the increased NP EBV loads could aggregate in the families and be affected by host genetics and environmental factor, EBV loads were obtained by 510 NP brushing samples from eligible unaffected individuals, who have two or more relatives affected with NPC, in 116 high\u2010risk NPC families. The correlation of relative pairs was estimated using S.A.G.E. (version 6.4, 2016), and host heritability of NP EBV loads was calculated with variance component models using SOLAR (version 8.4.2, 2019). In result, significant correlations of EBV loads were observed between parent\u2010offspring pairs and sibling\u2010sibling pairs (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001), but not in distant kin relationship pairs. Interestingly, after excluding the shared environmental factor within families, host genetics contributes significantly to NP EBV loads with a heritability of 56.41% (<jats:italic>P<\/jats:italic>\u2009=\u20091.00\u2009\u00d7\u200910<jats:sup>\u22127<\/jats:sup>), and its effect was slightly elevated (68.86%, <jats:italic>P<\/jats:italic>\u2009=\u20093.40\u2009\u00d7\u200910<jats:sup>\u22126<\/jats:sup>) in families with more NPC cases (\u22653). These findings indicate that additional host\u2010genetic variants involved in the EBV local NP mucosal behavior may be especially important for the development of NPC.<\/jats:p>","DOI":"10.1002\/jmv.26198","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T14:23:21Z","timestamp":1592576601000},"page":"3717-3725","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Nasopharyngeal Epstein\u2010Barr virus DNA loads in high\u2010risk nasopharyngeal carcinoma families: Familial aggregation and host heritability"],"prefix":"10.1002","volume":"92","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7595-8120","authenticated-orcid":false,"given":"Mei\u2010Qi","family":"Zheng","sequence":"first","affiliation":[{"name":"School of Public Health Sun Yat\u2010sen University  Guangzhou China"},{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer 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Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da\u2010Wei","family":"Yang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat\u2010sen University Cancer Center  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan\u2010Hua","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Sun Yat\u2010sen University Cancer Center  Guangzhou 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