TY - JOUR
T1 - rs641738C>T near MBOAT7 is associated with liver fat, ALT, and fibrosis in NAFLD
T2 - a meta-analysis
AU - EU-PNAFLD Investigators
AU - Teo, Kevin
AU - Abeysekera, Kushala W M
AU - Adams, Leon
AU - Aigner, Elmar
AU - Anstee, Quentin M
AU - Banales, Jesus M
AU - Banerjee, Rajarshi
AU - Basu, Priyadarshi
AU - Berg, Thomas
AU - Bhatnagar, Pallav
AU - Buch, Stephan
AU - Canbay, Ali
AU - Caprio, Sonia
AU - Chatterjee, Ankita
AU - Ida Chen, Yii-Der
AU - Chowdhury, Abhijit
AU - Daly, Ann K
AU - Datz, Christian
AU - de Gracia Hahn, Dana
AU - DiStefano, Johanna K
AU - Dong, Jiawen
AU - Duret, Amedine
AU - Emdin, Connor
AU - Fairey, Madison
AU - Gerhard, Glenn S
AU - Guo, Xiuqing
AU - Hampe, Jochen
AU - Hickman, Matthew
AU - Heintz, Lena
AU - Hudert, Christian
AU - Hunter, Harriet
AU - Kelly, Matt
AU - Kozlitina, Julia
AU - Krawczyk, Marcin
AU - Lammert, Frank
AU - Langenberg, Claudia
AU - Lavine, Joel
AU - Li, Lin
AU - Lim, Hong Kai
AU - Loomba, Rohit
AU - Luukkonen, Panu K
AU - Melton, Phillip E
AU - Mori, Trevor A
AU - Palmer, Nicholette D
AU - Parisinos, Constantinos A
AU - Pillai, Sreekumar G
AU - Qayyum, Faiza
AU - Reichert, Matthias C
AU - Romeo, Stefano
AU - Rotter, Jerome I
AU - Im, Yu Ri
AU - Santoro, Nicola
AU - Schafmayer, Clemens
AU - Speliotes, Elizabeth K
AU - Stender, Stefan
AU - Stickel, Felix
AU - Still, Christopher D
AU - Strnad, Pavel
AU - Taylor, Kent D
AU - Tybjærg-Hansen, Anne
AU - Umano, Giuseppina Rosaria
AU - Utukuri, Mrudula
AU - Valenti, Luca
AU - Wagenknecht, Lynne E
AU - Wareham, Nicholas J
AU - Watanabe, Richard M
AU - Wattacheril, Julia
AU - Yaghootkar, Hanieh
AU - Yki-Järvinen, Hannele
AU - Young, Kendra A
AU - Mann, Jake P
PY - 2021/1/1
Y1 - 2021/1/1
N2 - BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.METHODS: We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.RESULTS: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.CONCLUSION: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.
AB - BACKGROUND & AIMS: A common genetic variant near MBOAT7 (rs641738C>T) has been previously associated with hepatic fat and advanced histology in non-alcoholic fatty liver disease (NAFLD), however, these findings have not been consistently replicated in the literature. We aimed to establish whether rs641738C>T is a risk factor across the spectrum of NAFLD and characterize its role in the regulation of related metabolic phenotypes through meta-analysis.METHODS: We performed meta-analysis of studies with data on the association between rs641738C>T genotype and: liver fat, NAFLD histology, and serum ALT, lipids, or insulin. These included directly genotyped studies and population-level data from genome-wide association studies (GWAS). We performed random effects meta-analysis using recessive, additive, and dominant genetic models.RESULTS: Data from 1,066,175 participants (9,688 with liver biopsies) across 42 studies were included in the meta-analysis. rs641738C>T was associated with higher liver fat on CT/MRI (+0.03 standard deviations [95% CI: 0.02 - 0.05], pz=4.8x10-5) and diagnosis of NAFLD (OR 1.17 [95% CI 1.05 - 1.3], pz=0.003) in Caucasian adults. The variant was also positively associated with presence of advanced fibrosis (OR 1.22 [95% CI: 1.03 - 1.45], pz=0.021) in Caucasian adults using a recessive model of inheritance (CC+CT vs. TT). Meta-analysis of data from previous GWAS found the variant to be associated with higher ALT (pz=0.002) and lower serum triglycerides (pz=1.5x10-4). rs641738C>T was not associated with fasting insulin and no effect was observed in children with NAFLD.CONCLUSION: Our study validates rs641738C>T near MBOAT7 as a risk factor for the presence and severity of NAFLD in individuals of European descent.
U2 - 10.1016/j.jhep.2020.08.027
DO - 10.1016/j.jhep.2020.08.027
M3 - Article
C2 - 32882372
VL - 74
SP - 20
EP - 30
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 1
ER -