Key result
An 11-SNP weighted genetic risk score was significantly associated with an increased risk of NAFLD across multiple ethnic groups, with a 41% increased risk per standard deviation increase in the score.
Why the study?
Most genetic studies of nonalcoholic fatty liver disease (NAFLD) have been conducted in Whites, leaving the transportability of identified variants and genetic risk scores across diverse ethnic groups unclear.
Is an 11-SNP weighted Genetic Risk Score associated with NAFLD risk in an ethnically diverse cohort?
Case-Control (n=9,892)
Yes
Is an 11-SNP weighted Genetic Risk Score associated with NAFLD risk in an ethnically diverse cohort?
An 11-SNP genetic risk score successfully stratifies NAFLD risk across multiple ethnic groups, with a stronger association for NAFLD with cirrhosis.
Answers are grounded in this paper and cite their sources.
Supports GRS for NAFLD stratification in diverse groups; leaves open prospective validation and clinical utility.
Most genetic studies of nonalcoholic fatty liver disease (NAFLD) have been conducted in Whites. In this large and ethnically diverse cohort, we assessed the transportability of previously identified genetic variants for NAFLD, built a genetic risk score (GRS), and examined its association with NAFLD risk in multiple ethnic groups. Thirty previously identified genome‐wide association studies (GWAS) variants ( P < 5 × 10 −8 ) and 17 other variants associated with NAFLD were examined in a nested case‐control study of NAFLD (1,448 cases/8,444 controls) in this multi‐ethnic cohort study. We then built a GRS using 11 independent single‐nucleotide polymorphisms from these prior studies and examined its association with NAFLD by cirrhosis status across multiple ethnic groups. Of the 30 GWAS SNPs, 20 (67%) were replicated ( P < 0.05) in the pooled multi‐ethnic population. The highest percentage of replication was seen in Latinos (43%), followed by Japanese Americans (37%), Whites (17%), and Native Hawaiians and African Americans (≤10%). Several genetic variants, including those in PNPLA3 (patatin‐like phospholipase domain containing 3), HSD17B13 (hydroxysteroid 17‐beta dehydrogenase 13), TM6SF2 (transmembrane 6 superfamily member 2), GATAD2A (GATA zinc finger domain containing 2A), GCKR (glucokinase regulator), SUGP1 (SURP and G‐patch domain containing 1), MBOAT7 (membrane bound O‐acyltransferase domain containing 7), TRIB1 (tribbles pseudokinase 1), SAMM50 (sorting and assembly machinery component), and ERLIN1 (ER lipid raft associated 1)– CHUK (component of inhibitor of nuclear factor kappa B kinase complex)– CWF19L1 (CWF19 like cell cycle control factor 1) gene cluster, were replicated in at least two ethnic groups. An 11‐SNP weighted GRS was associated with NAFLD risk in the multi‐ethnic population (odds ratio [OR] per SD increase = 1.41; 95% confidence interval [CI] = 1.32‐1.50), as well as in each ethnic group (OR ranged from 1.30 in African Americans to 1.52 in Latinos). The GRS–NAFLD association was stronger for NAFLD with cirrhosis (OR = 1.67; 95% CI = 1.46‐1.92) compared to NAFLD without cirrhosis (OR = 1.37; 95% CI = 1.28‐1.46) ( P heterogeneity = 0.003). Conclusion: In this ethnically diverse cohort, we replicated several key genetic variants for NAFLD and showed the utility of GRS based on the risk alleles for NAFLD risk stratification in multiple ethnic groups.
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Wang et al. (2021) conducted a case-control in Nonalcoholic fatty liver disease (NAFLD) (n=9,892). 11-SNP weighted genetic risk score (GRS) vs. Lower genetic risk score (per SD increase) was evaluated on NAFLD risk (OR 1.41, 95% CI 1.32-1.50, p=6.59e-25). An 11-SNP weighted genetic risk score was significantly associated with an increased risk of NAFLD across multiple ethnic groups, with a 41% increased risk per standard deviation increase in the score.
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