Longitudinal association between overweight years, polygenic risk and NAFLD, significant fibrosis and cirrhosis
Veeral Ajmera 1 2, Na Wang 3, Hanfei Xu 4, Ching-Ti Liu 4, Michelle T Long 5Affiliations expand
- PMID: 36924053 PMCID: PMC10178778 (available on 2024-05-01) DOI: 10.1111/apt.17452
Abstract
Background: Adiposity amplifies the genetic risk of non-alcoholic fatty liver disease (NAFLD).
Aim: We evaluated the association between overweight-years, a cumulative exposure based on the product of the duration and severity of excess body weight (body mass index (BMI) ≥ 25 kg/m2 ), and genetic risk on liver fat and fibrosis.
Methods: This is a longitudinal analysis derived from a prospective cohort of adults in the Framingham Heart Study who underwent genotyping and vibration-controlled-transient-elastography with controlled attenuation parameter. Univariable and multivariable linear and logistic regression analyses were used to assess the association between overweight-years and liver fat and fibrosis. The association between genetic variants of liver fat (PNPLA3, TM6SF2, GCKR) and fibrosis (PNPLA3, TM6SF2, HSD17B13) was also assessed using a polygenic risk score.
Results: Our sample included 2478 participants (54% women) with mean age and BMI of 40 (±8.5) years and 26.5(±5.1) kg/m2 , respectively. The mean follow-up was 14(±0.9) years, and each participant underwent three study visits. The prevalence of NAFLD was 28.3% (n = 700), and 207 (8.4%) had clinically significant fibrosis. In age-, sex- and diabetes-adjusted multivariable analyses, overweight-years (per SD) had a strong association with NAFLD (aOR 3.53 [95% CI: 3.10-4.02], p < 0.001), clinically significant fibrosis (aOR 1.60 [95% CI: 1.40-1.84], p < 0.001) and cirrhosis (aOR 1.81 [95% CI: 1.38-2.37], p < 0.001). High-polygenic risk was significantly associated with liver fat and clinically significant fibrosis (p < 0.05).
Conclusion: Overweight-years is strongly associated with NAFLD and clinically significant fibrosis and combined with polygenic risk may assist in defining the trajectory of NAFLD.
Keywords: body mass; fibrosis; genetic risk; nonalcoholic fatty liver disease; steatosis.
