Table 1.

GWAS significant (p < 5 × 10^-8) SNP associations

SEX	CHR	BP	SNP	LOCUS	A1	A0	A1 FREQ	BETA	SE	P	P (other sex)
CRF-vo2max
Combined	1	112592672	rs269071	Intergenic1	A	G	0.63	0.031	0.005	3.6 × 10-10
Combined	2	179747068	rs142556838	CCDC141	C	T	0.91	0.049	0.008	2.9 × 10-9
Combined	2	179839888	rs10497529	CCDC141	G	A	0.96	0.085	0.013	1.0 × 10-11
Combined	3	38767315	rs6801957	SCN10A	T	C	0.41	0.030	0.005	1.7 × 10-10
Combined	5	65264090	rs251295	ERBB2IP	A	G	0.59	−0.027	0.005	2.3 × 10-8
Combined	5	121868475	rs111299422	Intergenic2	T	TA	0.69	−0.038	0.005	6.5 × 10-14
Combined	6	122089704	rs58730006	Intergenic3	A	AT	0.90	0.047	0.008	2.7 × 10-9
Combined	10	102552663	rs11190709	PAX2	G	A	0.11	−0.046	0.007	3.8 × 10-10
Combined	16	56803199	rs78291913	NUP93	C	T	0.99	−0.143	0.024	1.4 × 10-9
Combined	17	43668512	rs527325496	Intergenic4	C	CAAA	0.81	−0.036	0.006	4.2 × 10-9
Combined	17	44335579	rs139077859	LOC644172	G	A	0.79	−0.033	0.006	1.7 × 10-8
Combined	20	36849088	rs4811602	KIAA1755	G	A	0.53	−0.028	0.005	3.7 × 10-9
Malea	3	38773805	rs9809798	SCN10A	A	C	0.47	0.040	0.007	2.2 × 10-8	6.3 × 10-3
Maleb	5	121868475	rs111299422	Intergenic2	T	TA	0.69	−0.050	0.008	2.6 × 10-10	3.3 × 10-5
Malec	10	102553647	rs1006545	PAX2	G	T	0.11	−0.062	0.011	4.3 × 10-8	2.7 × 10-3
Maled	14	96864374	rs41317306	AK7	T	G	0.98	−0.137	0.024	2.2 × 10-8	5.1 × 10-1
CRF-slope
Combined	5	121868475	rs111299422	Intergenic2	T	TA	0.69	0.007	0.001	1.3 × 10-10
Combined	7	100546458	rs4582488	Integenic5	G	T	0.74	0.007	0.001	3.6 × 10-9
Combined	8	8317817	rs2921060	Intergenic6	A	C	0.55	0.006	0.001	1.6 × 10-8
Combined	8	10822431	rs35792458	XKR6	G	C	0.56	−0.006	0.001	1.5 × 10-8
Combined	8	11423072	rs12541800	Intergenic7	A	G	0.52	0.006	0.001	4.7 × 10-8
Combined	10	102554618	10:102554618_AT_A	PAX2	AT	A	0.11	0.012	0.002	1.5 × 10-13
Combined	12	24758480	rs4963772	Intergenic8	G	A	0.85	−0.009	0.001	5.8 × 10-11
Combined	12	33633599	rs7303356	Intergenic9	G	C	0.49	−0.006	0.001	1.5 × 10-10
Femalee	5	121868475	rs111299422	Intergenic2	T	TA	0.69	0.010	0.002	2.5 × 10-8	1.1 × 10-3
Malef	10	102553647	rs1006545	PAX2	G	T	0.11	0.012	0.002	6.0 × 10-12	2.0 × 10-5
Maleg	20	4131944	rs1741294	SMOX	C	G	0.96	0.016	0.003	6.0 × 10-9	6.0 × 10-1
PA
Combined	1	78450517	rs34517439	Intergenic10	C	A	0.88	0.316	0.058	4.6 × 10-8
Combined	5	87942506	rs10067451	LINC00461	G	A	0.89	0.333	0.060	3.0 × 10-8
Combined	5	152238114	5:152238114*	LOC101927134	TTTTTTTTTTTTC	T	0.71	0.230	0.042	4.1 × 10-8
Combined	9	128195657	rs1268539	Intergenic11	C	A	0.58	−0.214	0.038	1.9 × 10-8
Combined	10	21885577	rs34719019	MLLT10	A	T	0.73	0.242	0.042	9.7 × 10-9
Combined	17	43758125	rs62055696	CRHR1	A	G	0.78	−0.309	0.046	1.3 × 10-11
Combined	17	44326864	rs2696625	Intergenic12	A	G	0.77	−0.310	0.045	4.8 × 10-12
Combined	17	44828931	rs199533	NSF	G	A	0.79	−0.250	0.046	4.0 × 10-8
Combined	18	40768309	rs59499656	Intergenic13	A	T	0.66	−0.215	0.039	5.0 × 10-8
Femaleh	16	71464058	rs75986475	Intergenic14	C	G	0.88	−0.436	0.076	7.4 × 10-9	3.3 × 10-1
Femalei	16	80784797	rs13329850	CDYL2	C	G	0.74	−0.308	0.055	2.8 × 10-8	4.5 × 10-1
Femalej	17	43758125	rs62055696	CRHR1	A	G	0.78	−0.358	0.059	1.3 × 10-9	2.4 × 10-4
Femalek	17	44262581	17:44262581_A_C	KANSL1	A	C	0.83	−0.450	0.070	1.5 × 10-10	8.2 × 10-3
Malel	2	36592600	rs78661713	CRIM1	G	A	0.94	−0.700	0.128	4.8 × 10-8	6.1 × 10-1

Note: These are independent SNP associations determined by p value informed LD clumping (SNPs correlated 0.2 or greater in a 500 kb). 2 CRF-slope-associated SNPs (rs587631263, chr7; rs10623635, chr10) and 16 PA-associated SNPs (rs10828247, chr10; 15 chr17 SNPs listed in supplementary material) not available in LD reference data. LOCUS nearest gene, A1 effect allele, A0 reference allele, A1 FREQ effect allele frequency, BETA effect size (from BOLT-LMM approximation to infinitesimal mixed model), SE standard error of the effect size

*5:152238114_TTTTTTTTTTTTC_T

¹LOC643355 (+51.2kb), CTTNBP2NL (−346.1kb); ²MGC32805 (+53.7kb), LOC101927379 (−96.2kb); ³GJA1 (+318.8kb), HSF2 (−631kb); ⁴LOC644172 (−9.0kb), LRRC37A4P (+70.62kb); ⁵MUC3A (−0.593kb), ACHE (+52.87kb); ⁶SGK223 (+78.47kb), CLDN23 (−241.8kb); ⁷BLK (+0.964kb), LINC00208 (−10.97kb); ⁸LINC00477 (+21.38kb), BCAT1 (−204.5kb); ⁹SYT10 (+40.84kb), ALG10 (−541.6kb); ¹⁰FUBP1 (+5.74kb), DNAJB4 (−20.12kb); ¹¹MAPKAP1 (−4.015kb), GAPVD1 (+68.37kb); ¹²LOC644172 (+3.71kb), LRRC37A (−45.63kb); ¹³RIT2 (+72.65kb), SYT4 (−79.55kb); ¹⁴ZNF23 (−17.44kb), CALB2 (+39.72kb)

^aFemale BETA = 0.0163, SE = 0.0060: Q = 6.58, p = 1.0 × 10^-2; I² = 84.8%, 95% CI = 38.0% – 96.3% (ns_CRF = not significant at 0.05/7, for 7 CRF SNPs tested)

^bFemale BETA = −0.0271, SE = 0.0065: Q = 4.86, p = 2.8 × 10^-2; I² = 79.4%, 95% CI = 11.1–95.2% (ns_CRF)

^cFemale BETA = −0.0281, SE = 0.0094: Q = 5.34, p = 2.1 × 10^-2; I² = 81.3%, 95% CI = 20.3–95.6% (ns_CRF)

^dFemale BETA = 0.0136, SE = 0.0206: Q = 22.13, p < 0.001; I² = 95.5%, 95% CI = 86.8–98.5%

^emale BETA = 0.0038, SE = 0.0012: Q = 8.37, p = 3.8 × 10^-3; I² = 88.1%, 95% CI = 54.1–96.9%

^fFemale BETA = 0.0111, SE = 0.0026: Q = 0.04, p = 8.3 × 10^-1; I² = 0.0% (ns_CRF)

^gFemale BETA = 0.0021, SE = 0.0040: Q = 7.96, p = 4.8 × 10^-3; I² = 87.4%, 95% CI = 51.1–96.8%

^hMale BETA = −0.0893, SE = 0.0916: Q = 8.51, p = 3.5 × 10^-3; I² = 88.3%, 95% CI = 55.0–96.9%

ⁱMale BETA = 0.0503, SE = 0.0670: Q = 16.98, p < 0.001; I² = 94.1%, 95% CI = 81.4–98.1%

^jMale BETA = -0.2636, SE = 0.0718: Q = 1.03, p = 3.1 × 10^-1; I² = 3.0% (ns_PA = not significant at 0.05/5, for 5 PA SNPs tested)

^kMale BETA = −0.2258, SE = 0.0855: Q = 4.09, p = 4.3 × 10^-2; I² = 75.6%, 95% CI = 0.0–94.5% (ns_PA)

^lFemale BETA = 0.0542, SE = 0.1057: Q = 20.63, p < 0.001; I² = 95.2%, 95% CI = 85.5–98.4%