Table 1 Characteristics of summary level data used in the MR analysis

Studies

Sample size (n)

Female %

Mean age (SD)

Metabolomics platform

Ancestry

Amino acids (meta-analysis of metabolites GWAS)

 Fenland study

9736

53.5%

48.4 (7.4)

Biocrates p180 Kit

European

 EPIC-Norfolk study

5841

53.3%

59.8 (9.0)

Metabolon HD4

 INTERVAL trial

40,818

50.4%

43.5 (14.2)

Serum NMR platform (Nightingale) and Metabolon HD4

 GWAS by Shin et al. (2014)

7824

16.5%

57.1 (11.4)

Metabolon HD1

 GWAS by Draisma et al. (2015)

7478

53.5%

48.7 (12.7)

Biocrates p150 Kit

 GWAS by Kettunen et al. (2016)

24,925

53.9%

46.3 (9.7)

Serum NMR platform (Nightingale)

Studies

Cases

Controls

Inclusion criteria

Exclusion criteria

MAFLD (studies for discovery analysis)

 eMERGE

Adults: 710/paediatrics (≤ 21 years old): 396

Adults: 7725/paediatrics: 846

Adults: 54.8%/paediatrics: 44.2%

Adults: 63.5 (16.9)/paediatrics: 13.1 (5.4)

ICD9: 571.5, 571.8 and 571.9; ICD10: K75.81, K76.0 and K76.9

Alcohol dependence, alcoholic liver disease, alpha-1 antitrypsin deficiency, Alagille syndrome, liver transplant, cystic fibrosis, hepatitis, abetalipoproteinemia, LCAT (lecithin-cholesterol acyltransferase) deficiency, lipodystrophy, disorders of copper metabolism Reye’s syndrome, inborn errors of metabolism, HELLP (hemolysis, elevated liver enzymes and low platelets) syndrome, starvation and acute fatty liver

European

 UK Biobank

2558

395,241

NA

NA

ICD10: K74.0, K74.2, K75.8, K76.0 and K76.9

 Estonian Biobank

4119

190,120

NA

NA

ICD10: K74.0, K74.2, K75.8, K76.0 and K76.9

 FinnGen study (data freeze 4)

651

176,248

55.5%^a

52.1^a

ICD10: K76.0

NA

MAFLD (studies for replication analysis)

 GWAS by Anstee et al. (2020)

1483

17,781

47.3%^a

50.1 (13.0)^a

Liver biopsy

Excess alcohol intake (alcohol intake < 20 g/day for females; < 30 g/day for males), chronic viral hepatitis (hepatitis B and hepatitis C), autoimmune liver diseases, hereditary hemochromatosis, α1-antitrypsin deficiency, Wilson’s disease and drug-induced liver injury

European