Table 3.

Summary of the cross-omics annotation of the 17 candidate causal MASLD proteins

			AHCY	ANPEP	APOCI	APOE	CD33	FCGR2B	GRHPR	HM0X2	IL1RN	KRT18	KRT8	LPL	NCAN	0RM1	RBKS	SCG3	SORTI
		Direction of the association with MASLD	+	+	-	+	+	+	+	+	+	+	+	-	-	+	+	-	+
Discovery analysis	MR	MR using either MASLD GWAS sources				X	X		X	X	X	X			X			X	X
		MR using independent MASLD GWAS sources				X					X				X			X	X
		Colocalization				X					X	X
		MR replicated by Somalogic				X					X				X			X
	MASLD GWAS	Encoding gene genome widely associated with MASLD	X	X	X	X		X			X		X	X	X	X	X
Integrating with multi-dimensional data	Whole exome sequence data	Whole exome sequence data				X									X
	Liver imaging data	Encoding gene genomewide significantly associated with liver MRI			X	X									X		X
		MR with liver MRI				X					X				X
	Bulk gene expression data in liver tissues	Significant differential gene expression	X	X	X	X			X	X	X	X	X			X	X
		Cis-eQTL in or near the encoding gene		X			X	X											X
		MR of gene expression and MASLD		X				X											x
	Bulk gene expression data in visceral adipose tissues	Significant differential gene expression	X	X	X	X	X	X	X	X		X	X	X					X
		Cis-eQTL in or near the encoding gene		X			X	X	X	X
		MR of gene expression and MASLD					X	X	X	X
	RNA-seq data in liver tissue	Significant differential gene expression between MASLD and controls			X	X				X		X	X
	Single-cell RNA-seq data in the liver tissue	Significant differential gene expression between MASLD and controls in hepatocytes		X		X			X							X	X
		Significant differential gene expression between MASLD and controls in other liver cells except for hepatocytes	X			X	X	X		X		X	X			X	X		X
	Protein data in liver biopsies	Associated with liver steatosis features										X					X
		Druggability	X	X		X	X	X			X			X					X
External exploration	Pathway analysis	Enriched in fatty liver disease	X	X		X		X			X	X		X
		Enriched in cholesterol metabolism or serum total cholesterol measurement			X	X				X	X			X	X				X
		Enriched in liver tissue			X	X			X							X
	MR-PheWAS	Beneficial effect				X		X						X	X			X
		Unbeneficial effect				X											X
	Associated with BMI	Observational association	X	X	X	X	X	X	X	X	X	X	X	X	X	X	X	X	X
		MR with BMI (BMI as exposure)	X		X		X	X			X	X	X	X	X	X	X	X
		MR with BMI (BMI as outcome)				X												X
		Associated with MASLD after adjusted for BMI by multivariable MR		X	X	X			X	X	X	X	X	X		X	X		X

Proteins newly associated with MASLD in the current study are marked in bold.