Pleiotropy within gene variants associated with nonalcoholic fatty liver disease and traits of the hematopoietic system

Table 1 Phenome-wide association studies associations of variants influencing nonalcoholic fatty liver disease and their effect on blood-related traits

Variant	Trait1	Effect (beta)	P value
PNPLA3-rs738409. Chromosomal position: 44324727. Allele C MAF: 0.21
Blood-related trait	Platelet count	1.5369	2.8659e-45
	Hemoglobin concentration	-0.025607	9.0819e-35
	Platelet crit	0.0010141	3.6242e-29
	Mean corpuscular volume	-0.069237	9.4452e-16
	Hematocrit percentage	-0.063676	2.9494e-25
	Mean corpuscular hemoglobin	-0.031471	2.2846e-19
	Monocyte percentage	-0.035411	4.7043e-15
	Mean platelet (thrombocyte) volume	-0.016089	9.5385e-18
Liver diseases	K76 Other diseases of liver	-0.0022213	4.5111e-22
	K70 Alcoholic liver disease	-0.00087844	1.7073e-14
	K70-K77 Diseases of liver	-0.0028804	3.3855e-25
	K74 Fibrosis and cirrhosis of liver	-0.00075775	2.3186e-11
TM6SF2-rs58542926. Chromosomal position: 19379549. Allele C MAF: 0.975
Blood-related trait	Lymphocyte percentage	0.22273	1.8966e-19
	Neutrophil percentage	-0.20618	8.0938e-13
	Platelet crit	-0.001243	2.6606e-18
	Platelet count	-0.96935	1.5736e-08
	Red blood cell (erythrocyte) count	-0.008401	4.1569e-14
Liver diseases	K76 Other diseases of liver	-0.0020969	5.9013e-09
	K74 Fibrosis and cirrhosis of liver	-0.00078964	8.6924e-06
	K70-K77 Diseases of liver	-0.0023442	7.1296e-08
HSD17B13-rs72613567. Chromosomal position: 88231392. Allele T MAF: 0.27
Blood-related trait	Platelet count	-1.0628	6.675e-26
	Platelet crit	-0.00068946	2.0658e-16
	Mean platelet (thrombocyte) volume	0.012228	2.4506e-12
	Mean corpuscular hemoglobin	0.020281	2.7946e-10
Liver diseases	K70-K77 Diseases of liver	0.00095351	0.0002012
	K74 Fibrosis and cirrhosis of liver	0.00032971	0.0016351
	K70 Alcoholic liver disease	0.00030904	0.0034794
MBOAT7-TMC4 rs641738. Chromosomal position: 54676763. Allele T MAF: 0.44
Blood-related trait	Platelet crit	0.00079482	1.0509e-25
	Platelet count	0.84392	2.3213e-20
	White blood cell (leukocyte) count	-0.012957	3.4321e-05
	Mean platelet (thrombocyte) volume	0.0013881	0.37852
Liver diseases	K76 Other diseases of liver	0.0005036	0.0086505
	K70-K77 Diseases of liver	0.00058356	0.011748
	K74 Fibrosis and cirrhosis of liver	0.00019063	0.043702
	K70 Alcoholic liver disease	0.00017298	0.069988
GCKR-rs780094. Chromosomal position: 27741237. Allele C MAF: 0.38
Blood-related trait	Mean reticulocyte volume	0.16064	5.9197e-33
	Neutrophil percentage	-0.14035	2.7743e-19
	Neutrophil count	-0.037139	6.3804e-47
	Monocyte percentage	0.073076	7.914e-79
	Mean platelet (thrombocyte) volume	0.014342	1.3297e-18
	Platelet crit	-0.0013887	1.3581e-71
	Platelet count	-1.9052	6.2404e-92
	Hematocrit percentage	0.049511	4.3172e-21
Liver diseases	K76 Other diseases of liver	-0.00058708	0.0026207
	K70-K77 Diseases of liver	-0.0004415	0.060918
	K74 Fibrosis and cirrhosis of liver	-0.00011872	0.2169
	K75 Other inflammatory liver diseases	-0.00012854	0.13954
	K70 Alcoholic liver disease	9.7922e-05	0.31331

¹Letters and numbers such as K70, K76, K74 and K75 represent the codes for diseases (ICD10) in the United Kingdom Biobank. Approximately 30 million variants in the United Kingdom Biobank from the Gene ATLAS (http://geneatlas.roslin.ed.ac.uk) and Neale's database (http://www.nealelab.is/uk-biobank/) resources were comprehensively tested for their association with liver (ICD10 codes: K70, K76, K74 and K75) and blood cell-associated traits, including platelet, leukocyte and neutrophil counts. PNPLA3: Patatin-like Phospholipase Domain Containing protein 3; TM6SF2: Transmembrane 6 Superfamily Member 2; HSD17B13: Hydroxysteroid 17-Beta Dehydrogenase 13; MBOAT7: Membrane Bound O-Acyltransferase Domain Containing 7; TMC4: Transmembrane channel like 4; GCKR: Glucokinase regulator.