Additional file 1: of Smokescreen: a targeted genotyping array for addiction research

Smokescreen addiction regions and estimated imputed coverage. This file contains the addiction-related gene regions (chr 1–22) represented on the Smokescreen array and the estimated imputation-based coverage for each region in European (EUR), Asian (ASN), and African (YRI) populations. (XLSX 338 kb

Additional file 2: of GWASeq: targeted re-sequencing follow up to GWAS

Regional plots of associations for each targeted region. rs numbers and purple circles indicate the focal GWAS SNP that the region was selected around. Colored circles indicate degree of LD among SNPs. Grey circles indicate novel SNPs that lack LD information based on the 2012 release of the 1000 Genomes data. The rs number at figure top is centered around the location of the focal SNP. (ZIP 1921 kb

Additional file 1: of GWASeq: targeted re-sequencing follow up to GWAS

Boxplot of per-sample coverage by region, for each of the sequenced regions, by case–control status. (TIFF 8219 kb

Paired Liver:Plasma PFAS Concentration Ratios from Adolescents in the Teen-LABS Study and Derivation of Empirical and Mass Balance Models to Predict and Explain Liver PFAS Accumulation

Animal studies have pointed at the liver as a hotspot for per- and polyfluoroalkyl substances (PFAS) accumulation and toxicity; however, these findings have not been replicated in human populations. We measured concentrations of seven PFAS in matched liver and plasma samples collected at the time of bariatric surgery from 64 adolescents in the Teen-Longitudinal Assessment of Bariatric Surgery (Teen-LABS) study. Liver:plasma concentration ratios were perfectly explained (r2 > 0.99) in a multilinear regression (MLR) model based on toxicokinetic (TK) descriptors consisting of binding to tissue constituents and membrane permeabilities. Of the seven matched plasma and liver PFAS concentrations compared in this study, the liver:plasma concentration ratio of perfluoroheptanoic acid (PFHpA) was considerably higher than the liver:plasma concentration ratio of other PFAS congeners. Comparing the MLR model with an equilibrium mass balance model (MBM) suggested that complex kinetic transport processes are driving the unexpectedly high liver:plasma concentration ratio of PFHpA. Intratissue MBM modeling pointed to membrane lipids as the tissue constituents that drive the liver accumulation of long-chain, hydrophobic PFAS, whereas albumin binding of hydrophobic PFAS dominated PFAS distribution in plasma. The liver:plasma concentration data set, empirical MLR model, and mechanistic MBM modeling allow the prediction of liver from plasma concentrations measured in human cohort studies. Our study demonstrates that combining biomonitoring data with mechanistic modeling can identify underlying mechanisms of internal distribution and specific target organ toxicity of PFAS in humans