American journal of epidemiology
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Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. ⋯ After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 × 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.
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We analyzed data from a large population-based prospective cohort study of household contacts of tuberculosis patients in Lima, Peru, to estimate the importance of within-household transmission relative to community-based transmission. We identified all adults (older than 15 years of age) who had incident pulmonary tuberculosis diagnosed at any of 106 public health centers in Lima from September 2009 to August 2012. A total of 14,041 household contacts of 3,446 index patients were assessed for tuberculosis infection and disease. ⋯ However, a large proportion of infections among child and young-adult household contacts could have been the result of household exposure. Excess infection risk associated with household exposure accounted for 58% (95% confidence interval: 47, 66) of LTBI prevalence among exposed children younger than 1 year of age, 48% (95% confidence interval: 39, 57) among 10-year-old children, and 44% (95% confidence interval: 34, 51) among 15-year-old adolescents. These findings suggest that expanded access to preventive therapy for older children and young-adult household contacts of known tuberculosis cases may be beneficial.