Genetic Variants within NOGGIN, COL1A1, COL5A1, and IGF2 are Associated with Musculoskeletal Injuries in Elite Male Australian Football League Players: A Preliminary Study

Jacob, Ysabel; Anderton, Ryan S.; Cochrane Wilkie, Jodie L.; Rogalski, Brent; Laws, Simon M.; Jones, Anthony; Spiteri, Tania; Hince, Dana; Hart, Nicolas H.

doi:10.1186/s40798-022-00522-y

Sports Medicine - Open

Table 4 Negative binominal model of genetic variants and total number of muscle, tendon, ligament, and bone-related injuries

From: Genetic Variants within NOGGIN, COL1A1, COL5A1, and IGF2 are Associated with Musculoskeletal Injuries in Elite Male Australian Football League Players: A Preliminary Study

Variant		Muscle			Tendon			Ligament			Bone
Variant		IRR	p value	95% CI	IRR	p value	95% CI	IRR	p value	95% CI	IRR	p value	95% CI
All injuries
COL5A1	Intercept	0.026	0.000	[0.02 to 0.04]	0.012	0.000	[0.00 to 0.03]	0.037	0.000	[0.02 to 0.08]	0.10	0.000	[0.00 to 0.02]
(rs12722)	COL5A1	1.253	0.028	[1.03 to 1.53]	0.920	0.705	[0.60 to 1.42]	1.114	0.504	[0.81 to 1.53]	1.206	0.244	[0.88 to 1.65]
NOGGIN	Intercept	0.066	0.000	[0.04 to 0.11]	0.016	0.000	[0.01 to 0.04]	0.043	< 0.001	[0.02 to 0.10]	0.024	< 0.001	[0.01 to 0.04]
(rs1372857)	NOGGIN	0.813	0.050	[0.66 to 1.00]	0.802	0.285	[0.54 to 1.20]	1.038	0.833	[0.74 to 1.46]	0.820	0.159	[0.60 to 1.09]
COL1A1	Intercept	0.044	0.000	[0.03 to 0.07]	0.009	0.000	[0.00 to 0.02]	0.090	< 0.001	[0.05 to 0.17]	0.021	0.000	[0.01 to 0.04]
(rs1800012)	COL1A1	0.967	0.842	[0.69 to 1.34]	1.087	0.808	[0.55 to 2.13]	0.567	0.019	[0.35 to 0.91]	0.763	0.360	[0.43 to 1.36]
ACTN3	Intercept	0.055	0.000	[0.04 to 0.09]	0.012	0.000	[0.01 to 0.03]	0.045	0.000	[0.02 to 0.08]	0.016	0.000	[0.01 to 0.03]
(rs1815739)	ACTN3	0.845	0.226	[0.64 to 1.11]	0.861	0.594	[0.50 to 1.49]	1.031	0.884	[0.69 to 1.54]	0.972	0.896	[0.63 to 1.50]
SMAD6	Intercept	0.034	0.000	[0.02 to 0.05]	0.011	0.000	[0.00 to 0.03]	0.040	0.000	[0.02 to 0.08]	0.022	0.000	[0.01 to 0.04]
(rs2053423)	SMAD6	1.103	0.317	[0.91 to 1.34]	0.938	0.758	[0.62 to 1.41]	1.074	0.590	[0.83 to 1.40]	0.844	0.207	[0.65 to 1.10]
EMILIN1	Intercept	0.040	0.000	[0.03 to 0.06]	0.014	0.000	[0.01 to 0.03]	0.063	0.000	[0.04 to 0.10]	0.018	0.000	[0.01 to 0.03]
(rs2289360)	EMILIN1	1.040	0.672	[0.88 to 1.25]	0.824	0.320	[0.56 to 1.21]	0.826	0.141	[0.64 to 1.07]	0.905	0.506	[0.67 to 1.21]
CCL2	Intercept	0.023	0.000	[0.01 to 0.05]	0.013	< 0.001	[0.00 to 0.05]	0.091	< 0.001	[0.03 to 0.25]	0.042	< 0.001	[0.01 to 0.13]
(rs2857656)	CCL2	1.292	0.082	[1.00 to 1.23]	0.887	0.679	[0.50 to 1.56]	0.756	0.208	[0.49 to 1.17]	0.646	0.093	[0.39 to 1.08]
IGF2	Intercept	0.066	0.000	[0.04 to 0.11]	0.010	< 0.001	[0.00 to 0.03]	0.076	< 0.001	[0.03 to 0.18]	0.007	0.000	[0.00 to 0.02]
(rs3213221)	IGF2	0.814	0.097	[0.64 to 1.04]	0.996	0.988	[0.59 to 1.69]	0.799	0.277	[0.53 to 1.20]	1.393	0.093	[0.95 to 2.05]
COL12A1	Intercept	0.051	0.000	[0.03 to 0.10]	0.002	< 0.001	[0.00 to 0.01]	0.080	< 0.001	[0.04 to 0.17]	0.019	0.000	[0.00 to 0.05]
(rs970547)	COL12A1	0.937	0.623	[0.72 to 1.22]	1.698	0.084	[0.93 to 3.10]	0.812	0.181	[0.60 to 1.10]	0.920	0.639	[0.65 to 1.30]
Non-contact injuries
COL5A1	Intercept	0.025	0.000	[0.02 to 0.04]	0.011	0.000	[0.00 to 0.03]	0.005	0.000	[0.00 to 0.01]	0.11	< 0.001	[0.00 to 0.05]
(rs12722)	COL5A1	1.188	0.120	[0.96 to 1.48]	0.882	0.582	[0.57 to 1.38]	1.384	0.127	[0.91 to 2.10]	0.919	0.802	[0.48 to 1.78]
NOGGIN	Intercept	0.057	0.000	[0.04 to 0.09]	0.013	0.000	[0.00 to 0.03]	0.008	0.000	[0.00 to 0.02]	0.013	< 0.001	[0.00 to 0.05]
(rs1372857)	NOGGIN	0.810	0.054	[0.66 to 1.00]	0.811	0.324	[0.54 to 1.23]	1.081	0.712	[0.71 to 1.64]	0.837	0.549	[0.47 to 1.50]
COL1A1	Intercept	0.036	0.000	[0.02 to 0.06]	0.008	0.000	[0.00 to 0.02]	0.049	< 0.001	[0.02 to 0.13]	0.014	< 0.001	[0.00 to 0.05]
(rs1800012)	COL1A1	1.009	0.961	[0.72 to 1.42]	1.042	0.906	[0.52 to 2.08]	0.255	0.002	[0.11 to 0.60]	0.711	0.476	[0.28 to 1.82]
ACTN3	Intercept	0.051	0.000	[0.03 to 0.08]	0.009	0.000	[0.00 to 0.02]	0.015	0.000	[0.01 to 0.04]	0.014	< 0.001	[0.00 to 0.05]
(rs1815739)	ACTN3	0.795	0.110	[0.60 to 1.05]	0.991	0.974	[0.57 to 1.73]	0.745	0.275	[0.44 to 1.26]	0.746	0.448	[0.35 to 1.59]
SMAD6	Intercept	0.032	0.000	[0.02 to 0.05]	0.010	0.000	[0.00 to 0.03]	0.007	0.000	[0.00 to 0.02]	0.020	< 0.001	[0.01 to 0.07]
(rs2053423)	SMAD6	1.057	0.588	[0.87 to 1.29]	0.907	0.644	[0.60 to 1.37]	1.191	0.388	[0.80 to 1.77]	0.704	0.204	[0.41 to 1.21]
EMILIN1	Intercept	0.032	0.000	[0.02 to 0.05]	0.009	0.000	[0.00 to 0.02]	0.014	0.000	[0.01 to 0.03]	0.011	0.000	[0.00 to 0.03]
(rs2289360)	EMILIN1	1.069	0.483	[0.89 to 1.29]	0.950	0.798	[0.64 to 1.40]	0.834	0.313	[0.59 to 1.19]	0.897	0.693	[0.53 to 1.54]
CCL2	Intercept	0.022	0.000	[0.01 to 0.05]	0.014	< 0.001	[0.00 to 0.05]	0.007	< 0.001	[0.00 to 0.03]	0.031	< 0.001	[0.01 to 0.19]
(rs2857656)	CCL2	1.236	0.170	[0.91 to 1.67]	0.812	0.480	[0.46 to 1.45]	1.128	0.669	[0.65 to 1.96]	0.586	0.160	[0.28 to 1.24]
IGF2	Intercept	0.053	0.000	[0.03 to 0.09]	0.005	< 0.001	[0.00 to 0.02]	0.025	< 0.001	[0.01 to 0.07]	0.008	< 0.001	[0.00 to 0.04]
(rs3213221)	IGF2	0.838	0.175	[0.65 to 1.08]	1.272	0.389	[0.74 to 2.20]	0.648	0.082	[0.40 to 1.06]	1.071	0.846	[0.54 to 2.14]
COL12A1	Intercept	0.049	0.000	[0.02 to 0.10]	0.002	< 0.001	[0.00 to 0.01]	0.008	< 0.001	[0.00 to 0.03]	0.041	0.005	[0.00 to 0.37]
(rs970547)	COL12A1	0.894	0.405	[0.69 to 1.16]	1.750	0.079	[0.94 to 2.37]	1.085	0.765	[0.64 to 1.86]	0.561	0.170	[0.25 to 1.28]
Contact injuries
COL5A1	Intercept	0.003	< 0.001	[0.00 to 0.01]	0.001	< 0.001	[0.00 to 0.01]	0.035	0.000	[0.02 to 0.07]	0.001	0.000	[0.00 to 0.01]
(rs12722)	COL5A1	1.021	0.950	[0.53 to 1.97]	0.979	0.967	[0.35 to 2.76]	0.906	0.518	[0.67 to 1.22]	1.824	0.030	[1.06 to 3.13]
NOGGIN	Intercept	0.003	< 0.001	[0.00 to 0.01]	0.004	< 0.001	[0.01 to 0.03]	0.028	0.000	[0.02 to 0.05]	0.009	0.000	[0.00 to 0.03]
(rs1372857)	NOGGIN	0.930	0.824	[0.49 to 1.76]	0.528	0.216	[0.19 to 1.45]	0.998	0.989	[0.75 to 1.33]	0.768	0.288	[0.47 to 1.25]
COL1A1	Intercept	0.012	< 0.001	[0.00 to 0.06]	0.003	< 0.001	[0.00 to 0.04]	0.042	0.000	[0.02 to 0.08]	0.008	< 0.001	[0.00 to 0.03]
(rs1800012)	COL1A1	0.294	0.100	[0.07 to 1.26]	0.399	0.390	[0.05 to 3.24]	0.727	0.184	[0.46 to 1.16]	0.736	0.502	[0.30 to 1.80]
ACTN3	Intercept	0.002	0.000	[0.00 to 0.01]	0.002	< 0.001	[0.00 to 0.02]	0.037	0.000	[0.02 to 0.07]	0.003	0.000	[0.00 to 0.01]
(rs1815739)	ACTN3	1.273	0.545	[0.58 to 2.79]	0.638	0.521	[0.16 to 2.52]	0.840	0.364	[0.58 to 1.22]	1.552	0.151	[0.85 to 2.83]
SMAD6	Intercept	0.001	< 0.001	[0.00 to 0.01]	< 0.001	< 0.001	[0.00 to 0.01]	0.021	0.000	[0.01 to 0.04]	–	–	–
(rs2053423)	SMAD6	1.341	0.353	[0.72 to 2.49]	1.567	0.400	[0.55 to 4.46]	1.130	0.399	[0.85 to 1.50]	–	–	–
EMILIN1	Intercept	0.003	0.000	[0.00 to 0.01]	0.004	< 0.001	[0.00 to 0.02]	0.039	0.000	[0.02 to 0.06]	0.004	0.000	[0.00 to 0.01]
(rs2289360)	EMILIN1	1.040	0.889	[0.60 to 1.81]	0.447	0.163	[0.14 to 1.39]	0.830	0.143	[0.65 to 1.07]	1.175	0.491	[0.74 to 1.86]
CCL2	Intercept	0.001	< 0.001	[0.00 to 0.01]	< 0.001	< 0.001	[0.00 to 0.01]	0.031	< 0.001	[0.01 to 0.08]	0.005	< 0.001	[0.00 to 0.03]
(rs2857656)	CCL2	1.349	0.477	[0.59 to 3.08]	1.469	0.572	[0.39 to 5.58]	0.963	0.845	[0.66 to 1.41]	1.066	0.858	[0.53 to 2.13]
IGF2	Intercept	0.010	< 0.001	[0.00 to 0.05]	0.017	< 0.001	[0.00 to 0.17]	0.039	0.000	[0.02 to 0.08]	0.015	< 0.001	[0.00 to 0.06]
(rs3213221)	IGF2	0.559	0.146	[0.26 to 1.23]	0.249	0.028	[0.07 to 0.86]	0.865	0.392	[0.62 to 1.21]	0.603	0.108	[0.33 to 1.12]
COL12A1	Intercept	0.003	< 0.001	[0.00 to 0.02]	< 0.001	< 0.001	[0.00 to 0.01]	0.038	< 0.001	[0.01 to 0.10]	0.006	< 0.001	[0.00 to 0.03]
(rs970547)	COL12A1	0.987	0.974	[0.46 to 2.14]	3.506	0.225	[0.46 to 26.62]	0.896	0.562	[0.62 to 1.30]	0.946	0.856	[0.52 to 1.72]

Significant effects are bolded

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