Oxidative Gaseous Air Pollutant Exposure Interacts with PNPLA3-I148M Genotype to Influence Liver Fat Fraction and Multi-Omics Profiles in Young Adults
Abstract
PNPLA3-I148M genotype is the strongest predictive single-nucleotide polymorphism for liver fat. We examine whether PNPLA3-I148M modifies associations between oxidative gaseous air pollutant exposure (Oxwt) with i) liver fat and ii) multi-omics profiles of miRNAs and metabolites linked to liver fat. Participants were 69 young adults (17–22 years) from the Meta-AIR cohort. Prior-month residential Oxwt exposure (redox-weighted oxidative capacity of nitrogen dioxide and ozone) was spatially interpolated from monitoring stations via inverse-distance-squared weighting. Liver fat fraction was assessed by MRI. Serum miRNAs and metabolites were assayed via NanoString nCounter and LC-HRMS, respectively. Multi-omics factor analysis (MOFA) was used to identify latent factors with shared variance across omics layers. Multivariable linear regression models adjusted for age, sex, body mass index, and genotype with liver fat or MOFA factors as an outcome and examined PNPLA3 (rs738409; CC/CG vs. GG) as a multiplicative interaction term. Overall, a standard deviation difference in Oxwt exposure was associated with 8.9% relative increase in liver fat (p=0.04) and this relationship differed by PNPLA3 genotype (p-value for interaction term: pintx<0.001), whereby relative increases in liver fat for GG and CC/CG participants were 71.8% and 2.4%, respectively. There was no main effect of Oxwt on MOFA Factor 1 expression (p=0.85), but there was an interaction with PNPLA3 genotype (pintx=0.01),…
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Evidence Hub reads this as a cohort study, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 69 participants or records.
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