Table 3.

Converging evidence across analyses.

Gene	Locus Novelty	Common/Rare Coding SNPs	Nearest Gene	CVD Tissues (S-PrediXcan)	Mouse Kidney Single Cell Clusters	Supplementary Drug Table Reference	Count/Drug	Aorta IPA
ADK	novel	rs34868542	ADK	--↑x-xx		ST12	12	PP;SBP
FDFT1e	novel	NA	NA	x-↑↑↑xx		ST11, ST12	LOVASTATIN, LAPAQUISTAT ACETATE	-
PLAUe	novel	rs34868542	ADK	↑-xxxx-		ST11, ST12	55	-
PSMB7	novel	NA	NA	xx-x↑xx		ST12	5	-
PSMB9	novel	NA	NA	x--x↑x-		ST12, ST13	5	-
RAB10	novel	NA	NA	xx-xxx↑	Immune			-
RXFP2	novel	rs9603376	RXFP2	xxxx-↑x		ST12	4	-
ACHEb	known	rs374292503	Intergenic	−x↓↓↓↓↓	Tubules	ST12	56	DBP
ACP2e	known	rs11039216	SLC39A13	↑↑xx-xx		ST11	ATENOLOL, VERAPAMIL	-
AGERa	known	rs1061808	AGPAT1	x↑↑x↑-x		ST12	VITAMIN B12	DBP
ARL3	known	rs140473396	CNNM2	↑↑↑↑↑xx		ST12	CHEMBL384759	-
ARVCF	known	rs2240716	ARVCF	xx↓x↓xx		ST12, ST13	3	PP
AS3MT	known	rs140473396	CNNM2	--↑↑↑x-		ST12	LK-204545	-
ATP1B1f	known	rs4656180	NME7	xx↑x-x-		ST12	4	-
BACE1e	known	rs573455	CEP164	xxxx-↑x		ST11, ST12	28	-
BAG6	known	rs1800629	TNF	--↑↑↑xx		ST13	CARBAMAZEPINE	-
BCAR1e	known	rs12449170	CFDP1	−x↑x↑x-		ST11	CELECOXIB	SBP
C4Ab	known	rs1061808	AGPAT1	↓↓↓↓↓↓x		ST12	IMMUNE GLOBULIN	DBP
CDC16	known	rs11617448	CDC16	↑↑↑↑↑↑↑	Tubules			-
CDC25A	known	rs35979968	MAP4	↓↓↓↓↓-↓	Tubules			SBP
CEP68	known	rs74181299	CEP68	↑↑↑-↑-↑	Tubules			PP
CLCN6e	known	rs6669371	CLCN6	xx-x↓-↓	Tubules	ST11, ST13, ST14	9	-
COL21A1c	known	rs12203179/ rs115079907, rs200999181, rs2764043	COL21A1	xxx-↓x↓				-
CYP21A2a	known	rs1061808	AGPAT1	xx↑x↑xx		ST13	KETOCONAZOLE	-
FES	known	rs2071382	FES	−x↓↓↓-↓	Immune	ST13	NAPROXEN	SBP
FURIN	known	rs2071382	FES	xx↑xxxx		ST12	3	SBP
GFAPe	known	rs6503413	NMT1	xx↓xxx-		ST11, ST13, ST14	28	-
GUCY1A3e	known	rs3796592	GUCY1A3	xx↓xxx↓		ST11, ST14	6	SBP
GUCY1B3e	known	rs3796592	GUCY1A3	xx↓xx-x		ST11, ST14	6	SBP
HLA-Bg	known	rs1800629	TNF	---↑--x		ST12, ST13	6	-
HLA-DRB5b	known	rs1061808	AGPAT1	--↓↓↓-x		ST12	1D09C3	-
IGFBP3e	known	rs10260816	Intergenic	x↑-xxxx		ST11, ST14	FLUOROURACIL, CELECOXIB	-
MADDe	known	rs11039216	SLC39A13	↑↑-x--x		ST11	VERAPAMIL	-
NME6	known	rs35979968	MAP4	x--x↑↑↑	Glomerulus			-
NMT1	known	rs6503413	NMT1	--↑↑↑-↑	Immune	ST12	CHEMBL355497	SBP
NOTCH4b	known	rs1061808/ rs139341533	AGPAT1	x↓↓x↓↓x		ST12	NIROGACESTAT, REGN-421	DBP
NOV	known	rs11783703	NOV	x↓↑x↑xx		ST12	INSULIN	DBP
NPPBef	known	rs6669371	CLCN6	x↓xxxxx		ST11, ST14	OXYMETHOLONE, CARVEDILOL	-
NPR3e	known	rs12656497	NPR3	xxxxx↑x		ST11, ST12, ST13	4	-
NSF	known	rs80335285	GOSR2	↑↑-↑-xx		ST12	BITOSCANATE	-
NT5C2	known	rs140473396	CNNM2	xx↑x↑↓x		ST12	4	SBP
OPRL1	known	rs6090040	TCEA2	↓x↓x↓↓x		ST12	13	-
PDE3A	known	rs60691990/ rs141325069	Intergenic	xxx-xx-		ST12, ST13	19	-
PKN2	known	rs12035750	GTF2B	x-xxxx↑	Tubules	ST12	3	-
POC1B	known	rs11105354	ATP2B1	x--x-x↑	Tubules			-
PRKAR2Bd	known	rs12705390	AF086203	x-↑x--x		ST12	5	ALL
SBF2e	known	rs58068637	SWAP70	xx↓xxxx		ST11	PAROXETINE	-
SFXN2	known	rs140473396	CNNM2	−↑x-xx↑	Tubules			-
SLC12A2e	known	rs6595838	FBN2	x↑xx-xx		ST11, ST12	6	-
SLC4A7	known	rs2643826	SLC4A7	xx↓xxx↓	Immune			SBP
SRR	known	rs12952051	SMG6	↑↑-↑↑↑↑	Tubules	ST12	PYRIDOXAL PHOSPHATE, SERINE	-
THBS2a	known	rs533414974	Intergenic	xx↑-↑xx		ST12	BEVACIZUMAB, CORTICOTROPIN	DBP
TUBB1	known	rs6026739	ZNF831	xxxxxx↑		ST12, ST13	10	-

Selection criteria: evidence from at least 2 categories (coding variant gene, S-PrediXcan gene, gene implicated in mouse kidney single-cell expression, or drug target) and from at least 4 analyses. Gene = Gene showed enriched expression in one or more cell type in murine kidney single-cell RNA sequencing experiment, or was significant in genetically predicted gene expression analysis for any of the 45 tissues; Novel = Indicator variable denotes whether variants in a given gene region have previously been reported in genome-wide association studies of blood pressure traits. Sentinel SNPs = Sentinel SNP from common or rare variant analyses from each independent locus. Nearest Gene = Column reports genes that would have been identified if the nearest gene annotation strategy was used to link GWAS significant variants. CVD Tissues = Column identifies genes that were significantly associated with genetically predicted gene expression and blood pressure traits (using S-PrediXcan) in the following cardiovascular related tissues: heart atrial appendage, heart left ventricle, aorta, coronary artery, tibial artery, adrenal gland and kidney. Up (down) arrow indicates a positive (negative) association between GPGE and at least one blood pressure trait. Dash indicates data was not significant and x indicates data were unavailable. For a full-set of tissue specific results, see Supplementary Tables 8a–8c. Mouse kidney single-cell clusters = Column highlights the cell-type in which specific genes were enriched in murine single-cell RNA sequencing expression analyses. Supplementary Drug Table Reference = References the supplementary tables containing the gene-drug relationship. Count/Drug = Column summarizes drugs targeting genes when the number of drugs is ≤2 or the total number of drugs targeting the gene when the number of drugs is >2 which were identified to interrelate with the gene from the following databases: Guide to Pharmacology Interactions, Drugbank, PharmGKB, TDG Clinical Trials, TEND, and/or ChEMBL Interactions. Aorta IPA = Trait(s) for which the gene was identified in the aorta IPA network, SBP = systolic blood pressure; DBP = diastolic blood pressure; PP = pulse pressure;

^aGenetically predicted expression of these genes was positively associated with pulse pressure, inversely associated with DBP, and non-significant for SBP

^bGenetically predicted expression of these genes was positively associated with DBP, inversely associated with pulse pressure, and non-significant for SBP

^cGenetically predicted expression of these genes was positively associated with DBP and inversely associated with SBP and pulse pressure

^dGenetically predicted expression of these genes was positively associated with SBP and pulse pressure and inversely associated with DBP

^eTargeted by an antihypertensive medication

^fMendelian gene for hypertension

^gMendelian gene for hypotension