Table 2.

Statistically significant associations from the European ancestry analysis.

Method	Lead gene	Lead phenotype	Lead model	UKB carrier n (%)b	UKB p value	HNP carrier n (%)b	HNP p value	Meta p value
LMM	ALPL	Alkaline phosphatasea	Coding	257 (0.68%)	2.4 × 10−186	68 (0.65%)	2.5 × 10−39	5.3 × 10−223
LMM	SLC22A12	Uratea	Coding	314 (0.83%)	3.3 × 10−108	8 (0.46%)	2.1 × 10−4	5.5 × 10−111
LMM	GOT1	Aspartate aminotransferase	Coding	113 (0.3%)	5.4 × 10−58	28 (0.27%)	2.2 × 10−13	1.6 × 10−69
LMM	ABCA1	HDL cholesterola	Coding	449 (1.26%)	2.9 × 10−35	88 (0.98%)	2.3 × 10−10	4.9 × 10−44
LMM	APOB	LDL directa	LoF	96 (0.25%)	8.9 × 10−31	8 (0.09%)	9.7 × 10−11	8.5 × 10−40
LMM	GPT	Alanine aminotransferase	Coding	126 (0.33%)	1.9 × 10−28	40 (0.39%)	2.4 × 10−6	4.0 × 10−33
FET	HBB	Thalassaemia	LoF	1 (25%) /0 (0%)b	1.2 × 10−4	8 (47.06%)/5 (0.03%)b	1.7 × 10−21	1.2 × 10−24
LMM	TUBB1	Platelet counta	Coding	233 (0.59%)	1.2 × 10−15	71 (0.66%)	2.9 × 10−7	2.8 × 10−21
FET	JAK2	D45 Polycythaemia vera	Coding	13 (36.11%)/209 (0.61%)b	1.7 × 10−19	3 (10.34%)/77 (0.53%)b	5.4 × 10−4	1.7 × 10−19
LMM	KLF1	Mean corpuscular haemoglobin	LoF	27 (0.07%)	5.0 × 10−15	4 (0.04%)	8.9 × 10−4	2.3 × 10−17
LMM	APOA5	Triglycerides	LoF	42 (0.11%)	2.0 × 10−12	10 (0.11%)	1.1 × 10−2	1.0 × 10−13
LMM	GP9	Mean platelet volumea	Coding	85 (0.22%)	5.2 × 10−11	28 (0.27%)	1.5 × 10−3	3.1 × 10−13
LMM	ANGPTL3	Cholesterol	Coding	175 (0.46%)	3.2 × 10−10	67 (0.62%)	6.8 × 10−4	8.8 × 10−13
LMM	GCK	Glycated haemoglobin	Coding	58 (0.15%)	3.0 × 10−12	9 (0.17%)	8.4 × 10−2	9.3 × 10−13
LMM	TTN	I48 Atrial fibrillation and flutter	LoF	41 (2.38%)/311 (0.8%)b	1.1 × 10−11	12 (1.48%)/132 (0.8%)b	2.8 × 10−2	7.6 × 10−12
FET	COL4A4	R31 Unspecified haematuria	LoF	15 (1.2%)/51 (0.15%)b	1.1 × 10−8	5 (0.47%)/7 (0.05%)b	1.0 × 10−3	1.2 × 10−10
FET	BRCA2	Z40.0 Prophylactic surgery for malignant neoplasm risk-factors	LoF	7 (12.28%)/154 (0.45%)b	1.1 × 10−8	2 (9.52%)/56 (0.38%)b	3.1 × 10−3	1.4 × 10−10
LMM	CST3	Cystatin C	Coding	56 (0.15%)	9.6 × 10−52
LMM	SHBG	SHBG	Coding	149 (0.42%)	1.1 × 10−33
LMM	LDLR	Non-cancer illness code, self-reported: high cholesterol	Coding	79 (1.54%)/173 (0.49%)b	1.9 × 10−18
LMM	SLC45A2	Hair colour: Blonde	Coding	54 (1.16%)/112 (0.31%)b	1.2 × 10−17
LMM	STAB1	Median T2star in putamen (right)	LoF	38 (0.4%)	2.1 × 10−14
LMM	GP1BB	Mean platelet volumec	Coding	33 (0.08%)	3.0 × 10−12
LMM	SMAD6	6 mm weak meridian (right)	LoF	30 (0.11%)	3.1 × 10−11
LMM	CRP	C-reactive protein	Coding	66 (0.17%)	6.6 × 10−11
LMM	MC1R	Hair colour: Red	Coding	31 (1.75%)/222 (0.57%)b	2.2 × 10−10

D45, I48 and R31 refer to ICD-10-CM diagnosis codes, Median T2star is a measurement from a brain MRI, 6 mm weak meridian (right) is from keratometry of the right eye. When multiple phenotypes and/or models (coding, LoF) were significantly associated with a gene, only the lead phenotype and model are shown. When multiple genes were associated with a trait, only the top gene is shown. All results can be found in Supplementary Data 2

LMM linear mixed model, FET Fisher’s exact test, LoF loss of function, HDL high density lipoprotein, LDL low density lipoprotein, SHBG sex hormone binding globulin

^aAdditional genes associated with alkaline phosphatase include GPLD1, ASGR1, and ABCB11; with HDL cholesterol include LCAT, CETP, and SCARB1; with LDL direct include PCSK9; with platelet count include MPL and ITGA2B; with urate include SLC2A9; and with mean platelet volume include IQGAP2, GFI1B, and GP1BA

^bFor binary traits, the information shown is case n (%)/ctrl n (%)

^cAlthough this phenotype was included in the meta-analysis, this particular gene did not have carriers in the HNP cohort