Liver iron levels are associated with HFE-hemochromatosis genotype, diet, adiposity, and disease in the UK Biobank.

Undiagnosed C282Y+/+ individuals had significantly higher mean liver iron concentrations than diagnosed individuals.

• Mean MRLIC was highest in undiagnosed C282Y+/+ males and females (2.56 and 2.31 mg/g respectively)
• Diagnosed C282Y+/+ males and females had mean MRLIC of 1.23 and 1.51 mg/g respectively
• Differences were statistically significant: p=0.0001 for males and p=0.0004 for females
• The higher liver iron in undiagnosed versus diagnosed individuals is attributed likely to treatment in diagnosed cases
• Study analyzed 37,287 European ancestry UK Biobank participants with mean age 64.1 (SD: 7.6)

Higher alcohol intake was associated with higher MRI-estimated liver iron concentration.

• β=0.11, 95% CI: 0.09–0.11, p=6.0×10⁻¹²⁸
• Comparison was >30 vs. 1–14 units per week
• This was among the strongest environmental associations with MRLIC in the study
• Association was assessed using linear regression adjusted for age, sex, and genetic covariates

Frequent red and processed meat consumption was associated with higher liver iron concentration.

• β=0.08, 95% CI: 0.07–0.09, p=3.7×10⁻⁵⁴
• Comparison was ≥3 times per week versus none
• Association was assessed using linear regression adjusted for age, sex, and genetic covariates

Genetically predicted transferrin saturation was positively associated with liver iron concentration.

• β=0.22, 95% CI: 0.19–0.26, p=3.8×10⁻⁴⁶
• This was among the largest effect sizes observed for any factor in the study
• Association assessed using linear regression adjusted for age, sex, and genetic covariates

High waist-height ratio was associated with higher liver iron concentration, though the magnitude of effect was weak.

• β=0.01, 95% CI: 0.006–0.02, p=6.4×10⁻⁵
• The paper explicitly noted the 'magnitude was weak'
• This represents an adiposity measure distinct from BMI

Underweight BMI was associated with lower liver iron concentration.

• β=−0.06, 95% CI: −0.09 to −0.03, p=1.1×10⁻⁴
• Association was assessed using linear regression adjusted for age, sex, and genetic covariates

Proton pump inhibitor use was associated with lower liver iron concentration.

• β=−0.03, 95% CI: −0.04 to −0.03, p=3.5×10⁻¹⁷
• Association was assessed using linear regression adjusted for age, sex, and genetic covariates

Other HFE genotypes beyond C282Y homozygosity showed nominal increases in liver iron concentration compared to those without HFE genetic variants.

• The abstract states 'Other HFE genotypes had nominal increases versus those without HFE genetic variants'
• The study examined European ancestry participants with HFE genotypes and MRI-estimated liver iron concentrations
• The study population included 37,287 participants