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  • Mroueh, Rayan; Tanskanen, Tomas; Haapaniemi, Aaro; Salo, Tuula; Malila, Nea; Mäkitie, Antti; Pitkäniemi, Janne (2020)
    Background Reported patterns of familial aggregation of head and neck cancer (HNC) vary greatly, with many studies hampered by the limited number of subjects. Methods Altogether 923 early-onset ( Results Of all early-onset HNC families, only 21 (2.3%) had familial HNC cancers at any age and less than five familial early onset HNC cancers among first-degree relatives. The cumulative risk of HNC for siblings by age 60 (0.52%) was at population level (0.33%). No increased familial risk of early-onset HNC could be discerned in family members (SIR 2.68, 95% CI 0.32-9.68 for first-degree relatives). Conclusions Our study indicates that the cumulative and relative familial risk of early-onset HNC is modest in the Finnish population and, at most, only a minor proportion of early-onset HNCs are due solely to inherited genetic mutations.
  • Seyerle, A. A.; Sitlani, C. M.; Noordam, R.; Gogarten, S. M.; Li, J.; Li, X.; Evans, D. S.; Sun, F.; Laaksonen, M. A.; Isaacs, A.; Kristiansson, K.; Highland, H. M.; Stewart, J. D.; Harris, T. B.; Trompet, S.; Bis, J. C.; Peloso, G. M.; Brody, J. A.; Broer, L.; Busch, E. L.; Duan, Q.; Stilp, A. M.; O'Donnell, C. J.; Macfarlane, P. W.; Floyd, J. S.; Kors, J. A.; Lin, H. J.; Li-Gao, R.; Sofer, T.; Mendez-Giraldez, R.; Cummings, S. R.; Heckbert, S. R.; Hofman, A.; Ford, David; Li, Y.; Launer, L. J.; Porthan, K.; Newton-Cheh, C.; Napier, M. D.; Kerr, K. F.; Reiner, A. P.; Rice, K. M.; Roach, J.; Buckley, B. M.; Soliman, E. Z.; de Mutsert, R.; Sotoodehnia, N.; Uitterlinden, A. G.; North, K. E.; Chen, Y-D (2018)
    Thiazide diuretics, commonly used antihypertensives, may cause QT interval (QT) prolongation, a risk factor for highly fatal and difficult to predict ventricular arrhythmias. We examined whether common single-nucleotide polymorphisms (SNPs) modified the association between thiazide use and QT or its component parts (QRS interval, JT interval) by performing ancestry-specific, transethnic and cross-phenotype genome-wide analyses of European (66%), African American (15%) and Hispanic (19%) populations (N = 78 199), leveraging longitudinal data, incorporating corrected standard errors to account for underestimation of interaction estimate variances and evaluating evidence for pathway enrichment. Although no loci achieved genome-wide significance (P <5 x 10(-8)), we found suggestive evidence (P <5 x 10(-6)) for SNPs modifying the thiazide-QT association at 22 loci, including ion transport loci (for example, NELL1, KCNQ3). The biologic plausibility of our suggestive results and simulations demonstrating modest power to detect interaction effects at genome-wide significant levels indicate that larger studies and innovative statistical methods are warranted in future efforts evaluating thiazide-SNP interactions.