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. 2007 May 10;115(8):1210–1215. doi: 10.1289/ehp.9855

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Exploration of nonlinear association of tibia lead concentration with annual rate of cognitive decline, by class of HFE genotype. The lines indicate curvilinear trends estimated from the penalized spline method. Among HFE wild-types, the optimal degree of smoothing was 1, meaning that the association between tibia lead and annual cognitive decline was nearly linear, but among variant allele carriers, the association tended to deviate from linearity (p = 0.08), with an optimal 1.68 degree of smoothing. The model was adjusted for age, years of education, nonsmoker, former smoker, pack-years, nondrinker, alcohol consumption, English as first language, computer experience, and diabetes.