Appendix 1—table 2. The association between the multi-ancestry polygenic risk score (PRS) and prostate cancer aggressiveness in Million Veteran Program (MVP) participants from European, African, and Hispanic populations.

PRS categories were determined based on the distribution in controls in each replication study. ORs and 95% CIs were estimated from logistic regression models adjusting for age and principal components of ancestry. Heterogeneity was assessed via a Q statistic between effects estimates with corresponding tests of significance.

	Aggressive cases vs. controls					Nonaggressive cases vs. controls
PRS category	Controls	Cases	OR	95% CI	p-Value	Controls	Cases	OR	95% CI	p-Value	P-heterogeneity
European ancestry
[0–10%]	21,022	82	0.47	(0.37–0.59)	5.16E-10	21,022	258	0.31	(0.27–0.36)	4.43E-66	4.86E-03
(10–20%]	21,021	96	0.55	(0.44–0.68)	1.63E-07	21,021	423	0.51	(0.46–0.57)	6.29E-34	0.61
(20–30%]	21,021	118	0.67	(0.54–0.83)	1.76E-04	21,021	520	0.63	(0.57–0.70)	1.45E-19	0.60
(30–40%]	21,022	156	0.89	(0.73–1.07)	2.14E-01	21,022	656	0.79	(0.72–0.87)	8.87E-07	0.30
(40–60%]	42,042	352	1.00 (ref.)			42,042	1658	1.00 (ref.)
(60–70%]	21,022	245	1.39	(1.18–1.64)	7.32E-05	21,022	1120	1.35	(1.25–1.45)	6.55E-14	0.71
(70–80%]	21,021	272	1.55	(1.32–1.82)	7.13E-08	21,021	1392	1.67	(1.55–1.79)	1.84E-42	0.41
(80–90%]	21,021	335	1.91	(1.64–2.22)	4.51E-17	21,021	1801	2.15	(2.00–2.30)	5.69E-105	0.16
(90–100%]	21,022	554	3.17	(2.77–3.63)	2.72E-63	21,022	3151	3.71	(3.48–3.94)	<4.35E-283	0.04
(99–100%]	2,103	112	6.49	(5.22–8.07)	1.08E-63	2103	589	6.77	(6.10–7.51)	4.35E-283	0.73
African ancestry
[0–10%]	5,337	29	0.35	(0.24–0.53)	2.96E-07	5337	163	0.35	(0.30–0.42)	2.50E-33	0.98
(10–20%]	5,336	45	0.55	(0.40–0.77)	4.23E-04	5336	247	0.54	(0.46–0.62)	2.28E-17	0.88
(20–30%]	5,336	45	0.55	(0.40–0.77)	4.98E-04	5336	306	0.66	(0.58–0.76)	1.74E-09	0.33
(30–40%]	5,336	70	0.86	(0.65–1.14)	3.05E-01	5336	318	0.69	(0.61–0.79)	3.43E-08	0.16
(40–60%]	10,672	163	1.00 (ref.)			10,672	920	1.00 (ref.)
(60–70%]	5,336	121	1.50	(1.18–1.90)	8.14E-04	5336	556	1.21	(1.08–1.35)	7.65E-04	0.11
(70–80%]	5,336	131	1.62	(1.28–2.04)	4.97E-05	5336	659	1.43	(1.29–1.59)	1.88E-11	0.36
(80–90%]	5,336	151	1.89	(1.51–2.36)	2.59E-08	5336	819	1.78	(1.61–1.97)	9.21E-30	0.64
(90–100%]	5,337	262	3.31	(2.71–4.03)	4.66E-32	5337	1,224	2.66	(2.43–2.92)	8.99E-97	0.05
(99–100%]	534	45	5.840	(4.14–8.22)	5.79E-24	534	220	4.77	(4.02–5.66)	1.62E-71	0.30
Hispanic
[0–10%]	2061	2	0.12	(0.03–0.50)	3.69E-03	2061	21	0.31	(0.20–0.50)	8.67E-07	0.21
[10–20%]	2060	6	0.36	(0.15–0.87)	2.23E-02	2060	31	0.46	(0.31–0.69)	1.29E-04	0.61
(20–30%]	2060	6	0.36	(0.15–0.86)	2.12E-02	2060	47	0.70	(0.50–0.98)	4.00E-02	0.16
(30–40%]	2060	17	1.04	(0.58–1.87)	9.04E-01	2060	59	0.88	(0.65–1.21)	4.39E-01	0.64
(40–60%]	4,120	33	1.00 (ref.)			4120	133	1.00 (ref.)
(60–70%]	2060	20	1.21	(0.69–2.11)	5.05E-01	2060	85	1.28	(0.97–1.68)	8.50E-02	0.87
(70–80%]	2060	24	1.47	(0.86–2.49)	1.55E-01	2060	136	2.06	(1.61–2.63)	7.82E-09	0.26
(80–90%]	2060	22	1.33	(0.77–2.29)	3.01E-01	2060	136	2.05	(1.61–2.62)	8.69E-09	0.15
(90–100%]	2060	31	1.92	(1.17–3.15)	9.37E-03	2060	217	3.30	(2.64–4.12)	7.46E-26	0.05
(99–100%]	206	4	2.580	(0.91–7.38)	7.61E-02	206	46	7.15	(4.96–10.3)	3.99E-26	0.07