https://www.ncbi.nlm.nih.gov/pubmed/31255630 NAFLD
Dig Liver Dis. 2019 Jun 26. pii: S1590-8658(19)30630-9. doi: 10.1016/j.dld.2019.05.029. [Epub ahead of print]

Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese childrenand adolescents.

Zusi C1, Mantovani A2, Olivieri F3, Morandi A3, Corradi M3, Miraglia Del Giudice E4, Dauriz M2, Valenti L5, Byrne CD6, Targher G2, Maffeis C7.
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Abstract

BACKGROUND:
Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in children and adolescents in Western countries. Complex traits arise from the interplay between environmental and genetic factors in the pathogenesis of NAFLD.

AIMS:
We examined the association between NAFLD and eleven single nucleotide polymorphisms (SNPs) at genetic loci potentially associated with liver damage (GCKR, MBOAT7, GPR120), oxidative stress (SOD2), lipid metabolism (PNPLA3, TM6SF2, LPIN1, ELOVL2, FADS2, MTTP) and fibrogenesis (KLF6) in a paediatric population. A genetic risk score (GRS) was performed taking into account both these SNPs and clinical risk factors.

METHODS:
We recruited a cohort of 514 obese children and adolescents (mean age [±SD]: 11.2 ± 2.8 years, z-BMI 3.3 ± 0.8). NAFLD was identified by ultrasonography. Genotyping was performed by TaqMan-based RT-PCR system.

RESULTS:
The overall prevalence of NAFLD was 67.5% (347 patients). Among the eleven genotyped SNPs, the genetic variants in TM6SF2 rs58542926 (OR = 4.13, p = 0.002), GCKR rs1260326 (OR = 1.53, p = 0.003), PNPLA3 rs738409 (OR = 1.58, p = 0.004) and ELOVL2 rs2236212 (OR = 1.34, p = 0.047) were significantly associated with a higher risk of NAFLD. Addition of a 11-polymorphism GRS to established clinical risk factors significantly (albeit modestly) improved the discriminatory capability of the regression model for predicting the risk of NAFLD (with SNPs C-statistic 0.81 [95%CI 0.75-0.88] vs. 0.77 [0.70-0.84] without SNPs; p = 0.047).

CONCLUSIONS:
NAFLD was strongly associated with three genetic variants, TM6SF2 rs58542926, PNPLA3 rs738409 and GCKR rs1260326, and more slightly with ELOVL2 rs2236212, in obese children and adolescents. Addition of a 11-polymorphism GRS to clinical risk factors improved the predictability of NAFLD.