Table 2.

Significant associations of the rs4293393 (A/G) UMOD variant with clinical phenotypes among non-Hispanic White patients in the Million Veteran Program and Replication results from BioVU (Vanderbilt’s Biobank) and UK Biobank

Clinical phenotypes	Million Veteran Program					Replication cohorts
	PheWAS code description	Cases	Controls	OR (95% CI) per copy of the A allele	P value	BioVU	UK Biobank
Increased risk
CKD	CKD	56,757	354,568	1.22 (1.20–1.24)	5.90 × 10−111	Yesa	Yes
	CKD, stages I–II	8236	411,510	1.11 (1.07–1.19)	3.29 × 10−05	Nob	No
	CKD, stage III	37,099	379,128	1.24 (1.21–1.26)	2.79 × 10−86	Yes	No
	CKD, stage IV	8918	416,152	1.23 (1.19–1.29)	1.33 × 10−23	Yes	No
Diabetic kidney disease	Type 2 diabetes with renal manifestations	21,706	395,843	1.11 (1.08–1.13)	2.76 × 10−14	No	No
Proteinuria	Proteinuria	9030	411,051	1.10 (1.05–1.14)	4.31 × 10−06	Yes	No
End-stage kidney disease and related disorders	End-stage renal disease	5334	421,018	1.17 (1.11–1.24)	2.40 × 10−09	No	Yes
	Renal failure, NOS	5950	415,270	1.16 (1.10–1.22)	4.20 × 10−09	No	Yes
	Secondary hyperparathyroidism of renal origin	4716	421,292	1.21 (1.14–1.28)	1.69 × 10−11	No	No
	Anemia of CKD	7330	416,175	1.20 (1.14–1.25)	7.31 × 10−15	No	Yes
	Disorders resulting from impaired renal function	6104	418,597	1.17 (1.12–1.23)	1.79 × 10−10	No	No
Acute kidney injury	Acute renal failure	37,825	367,058	1.06 (1.04–1.09)	5.50 × 10−10	No	Yes
Electrolyte imbalance	Electrolyte imbalance	51,136	338, 927	1.04 (1.02–1.05)	2.33 × 10−05	No	No
Hyperkalemia	Hyperpotassemia	15,510	395,633	1.07 (1.04–1.10)	2.62 × 10−05	No	Yes
Hypertension and complications	Hypertension	303,313	102,754	1.03 (1.02–1.05)	2.11 × 10−06	No	Yes
	Essential hypertension	301,525	104,191	1.03 (1.02–1.05)	3.08 × 10−06	No	Yes
	Hypertensive CKD	30,565	381,368	1.20 (1.17–1.22)	1.89 × 10−53	No	Yes
	Hypertensive heart or renal disease	53,251	346,382	1.10 (1.09–1.12)	5.11 × 10−29	No	Yes
Gout	Gout	38,796	379,147	1.04 (1.02–1.06)	1.94 × 10−05	Yes	No
Anemia	Anemia of chronic disease	13,675	403,118	1.13 (1.09–1.16)	9.05 × 10−13	No	No
	Other anemias	76,540	313,641	1.03 (1.02–1.05)	2.00 × 10−05	No	Yes
Decreased risk
UTIs	UTI	42,133	351,924	0.94 (0.92–0.96)	1.21 × 10−10	Yes	No
Urinary calculi	Urinary calculus	36,238	376,038	0.85 (0.83–0.86)	1.45 × 10−64	Yes	Yes
	Calculus of the kidney	30,249	383,255	0.83 (0.81–0.85)	4.27 × 10−69	Yes	Yes
	Calculus of the ureter	8817	413,932	0.81 (0.78–0.84)	1.77 × 10−29	Yes	Yes
	Calculus of the lower urinary tract	2784	423,008	0.81 (0.76–0.87)	4.93 × 10−10	No	Yes
	Hydronephrosis	6559	415,441	0.88 (0.84–0.92)	9.20 × 10−09	No	Yes
Hematuria	Hematuria	36,418	368,018	0.95 (0.93–0.97)	4.40 × 10−07	No	Yes
	Gross hematuria	12,904	405, 647	0.94 (0.91–0.97)	3.26 × 10−05	No	No

BioVU, biorepository; CKD, chronic kidney disease; NOS, not otherwise specified; OR, odds ratio; PheWAS, phenome-wide association study; UTI, urinary tract infection.

All associations listed were significant at the Bonferroni-corrected significance level of 3.27 × 10⁻⁰⁵.

^aYes means that the association was replicated in BioVU or the UK Biobank.

^bNo means that the association was not replicated in BioVU or the UK Biobank.