Study of association of PAX6 polymorphisms with susceptibility to high myopia in a Japanese population

Figures & data

Table 1 Clinical characteristics of the study populations

Parameters	High myopiab (n=1,585)	Controlsc (n=1,011)
Male, %	44.2	41.6
Mean age,a (years)	38.8±12.2	58.2±12.3
Age range	(12, 78)	(20, 87)
Mean SE,a diopter (D)
Right eyes	−10.94±2.06	0.48±0.64
Left eyes	−10.82±2.07	0.48±0.63
Range of SE
Right eyes	(−4.50, −22.75)	(−1.00, 3.50)
Left eyes	(−4.50, −24.50)	(−1.00, 3.00)
Mean AL,a mm
Right eyes	27.55±1.22	23.22±0.80
Left eyes	27.51±1.24	23.20±0.79
Range of AL
Right eyes	(23.92, 33.85)	(18.76, 25.96)
Left eyes	(23.99, 34.74)	(18.99, 26.05)

Notes:

a Data presented are mean ± standard deviation.

b High myopia cases defined as SE<−9.0 D in at least one eye.

c Controls defined as SE≥−1.0 D in both eyes.

Abbreviations: AL, axial length; SE, spherical equivalent.

Table 2 Genotypic association results for five PAX6 SNPs after stratification according to spherical equivalent refractive error

SNP	Position on Chr 11 (build 37.1)	Alleles (1>2)	Risk allele	Phenotype			n	Genotype ([R/R]/[R/nR]/[nR/nR]) frequency, %	Genetic modelsa
					Criteria for SE (D)	Eye meeting criteria			Additive model		Dominant model		Recessive model
									P-value	OR (95% CI)	P-value	OR (95% CI)	P-value	OR (95% CI)
rs662702	31,809,070	G>A	G	Controls	≥−1	Both	1,011	79.4/19.1/1.5
				Cases	<−9	At least one	1,585	80.8/17.6/1.5	0.480	1.09 (0.86–1.37)	0.379	1.46 (0.63–3.39)	0.603	1.07 (0.83–1.38)
					<−9	Both	1,252	80.8/17.4/1.8	0.643	1.06 (0.83–1.36)	0.486	1.36 (0.58–3.21)	0.764	1.04 (0.79–1.38)
					<−11	Both	394	82.3/14.9/2.8	0.663	1.07 (0.78–1.47)	0.662	0.81 (0.31–2.12)	0.497	1.14 (0.78–1.65)
					<−13	Both	130	85.3/12.4/2.3	0.399	1.22 (0.76–1.94)	0.948	1.05 (0.27–4.06)	0.329	1.31 (0.75–2.29)
					<−15	Both	36	88.9/11.1/0.0	0.171	1.89 (0.69–5.17)	nd	nd	0.236	1.85 (0.62–5.48)
rs3026393	31,812,215	T>G	G	Controls	≥−1	Both	1,011	22.7/48.6/28.8
				Cases	<−9	At least one	1,585	22.7/50.0/27.3	0.791	0.98 (0.85–1.13)	0.950	1.01 (0.80–1.26)	0.607	0.94 (0.74–1.19)
					<−9	Both	1,252	22.4/50.3/27.2	0.851	0.99 (0.85–1.15)	0.876	1.02 (0.80–1.30)	0.629	0.94 (0.72–1.22)
					<−11	Both	394	22.8/52.9/24.3	0.844	1.02 (0.83–1.25)	0.214	1.23 (0.89–1.71)	0.335	0.85 (0.60–1.19)
					<−13	Both	130	24.0/55.8/20.2	0.437	1.12 (0.84–1.48)	0.078	1.54 (0.94–2.52)	0.632	0.89 (0.55–1.43)
					<−15	Both	36	25.0/61.1/13.9	0.384	1.24 (0.76–2.02)	0.068	2.32 (0.87–6.20)	0.769	0.89 (0.39–2.00)
rs644242	31,812,801	G>T	G	Controls	≥−1	Both	1,011	79.5/19.1/1.4
				Cases	<−9	At least one	1,585	81.1/17.5/1.5	0.493	1.08 (0.86–1.37)	0.366	1.49 (0.63–3.51)	0.623	1.07 (0.82–1.38)
					<−9	Both	1,252	81.1/17.2/1.7	0.641	1.06 (0.83–1.36)	0.460	1.39 (0.58–3.35)	0.771	1.04 (0.79–1.38)
					<−11	Both	394	82.9/14.5/2.6	0.519	1.11 (0.81–1.53)	0.773	0.86 (0.32–2.35)	0.389	1.18 (0.81–1.72)
					<−13	Both	130	86.0/11.6/2.3	0.315	1.27 (0.79–2.04)	0.960	1.04 (0.27–4.04)	0.240	1.39 (0.79–2.45)
					<−15	Both	36	91.7/8.3/0.0	0.069	2.51 (0.79–7.98)	nd	nd	0.093	2.56 (0.75–8.72)
rs3026390	31,813,509	A>G	G	Controls	≥−1	Both	1,011	22.5/48.8/28.7
				Cases	<−9	At least one	1,585	22.8/50.0/27.2	0.758	0.98 (0.85–1.13)	0.992	1.00 (0.80–1.26)	0.596	0.94 (0.74–1.19)
					<−9	Both	1,252	22.5/50.4/27.1	0.819	0.98 (0.84–1.15)	0.907	1.01 (0.80–1.29)	0.611	0.93 (0.72–1.21)
					<−11	Both	394	22.7/53.3/24.0	0.860	1.02 (0.83–1.25)	0.207	1.23 (0.89–1.72)	0.310	0.84 (0.60–1.18)
					<−13	Both	130	23.8/56.2/20.0	0.468	1.11 (0.84–1.47)	0.084	1.53 (0.93–2.50)	0.598	0.88 (0.55–1.42)
					<−15	Both	36	25.0/61.1/13.9	0.399	1.23 (0.76–2.01)	0.075	2.28 (0.85–6.09)	0.764	0.88 (0.39–1.99)
rs667773	31,815,362	C>T	C	Controls	≥−1	Both	1,011	79.6/18.9/1.5
				Cases	<−9	At least one	1,585	81.1/17.4/1.5	0.502	1.08 (0.86–1.37)	0.344	1.51 (0.65–3.54)	0.644	1.06 (0.82–1.38)
					<−9	Both	1,252	81.1/17.2/1.7	0.637	1.06 (0.83–1.36)	0.438	1.41 (0.59–3.37)	0.775	1.04 (0.79–1.37)
					<−11	Both	394	83.0/14.4/2.6	0.540	1.10 (0.80–1.52)	0.797	0.88 (0.32–2.38)	0.416	1.17 (0.80–1.70)
					<−13	Both	130	86.6/11.0/2.4	0.264	1.31 (0.81–2.12)	0.969	1.03 (0.27–3.97)	0.187	1.46 (0.82–2.60)
					<−15	Both	36	91.7/8.3/0.0	0.071	2.50 (0.79–7.93)	nd	nd	0.095	2.55 (0.75–8.67)

Notes:

a Multiple inheritance models were applied in analysis of genotype data to assess each risk allele: additive (R/R vs R/nR vs nR/nR), dominant (R/R + R/nR vs nR/nR), and recessive (R/R vs R/nR + nR/nR) models were assessed. P-values and ORs were adjusted for age and sex.

Abbreviations: 1, major allele; 2, minor allele; Chr, chromosome; CI, confidence interval; D, diopter; nd, not detected; nR, non-risk allele; OR, odds ratio; PAX6, paired box 6; R, risk allele; SE, spherical equivalent; SNPs, single nucleotide polymorphisms.

Table 3 Genotypic association results for five PAX6 SNPs after stratification by axial length

SNP	Position on Chr 11 (build 37.1)	Alleles (1>2)	Risk allele	Phenotype			n	Genotype ([R/R]/[R/nR]/[nR/nR]) frequency, %	Genetic modelsa
					Criteriafor AL (mm)	Eye meeting criteria			Additive model		Dominant model		Recessive model
									P-value	OR (95% CI)	P-value	OR (95% CI)	P-value	OR (95% CI)
rs662702	31,809,070	G>A	G	Controls	<24	Both	779	78.7/19.5/1.8
				Cases	>26	Both	1,247	81.1/17.3/1.5	0.436	1.11 (0.85–1.47)	0.159	2.00 (0.77–5.20)	0.665	1.07 (0.79–1.45)
					>28	Both	361	83.4/14.6/2.0	0.149	1.32 (0.90–1.92)	0.168	2.36 (0.68–8.15)	0.237	1.30 (0.84–2.01)
					>29	Both	111	86.4/11.8/1.8	0.115	1.56 (0.88–2.78)	0.475	1.79 (0.34–9.43)	0.106	1.75 (0.87–3.51)
					>30	Both	30	86.7/10.0/3.3	0.350	1.52 (0.60–3.85)	0.930	1.10 (0.12–10.05)	0.258	1.90 (0.59–6.11)
rs3026393	31,812,215	T>G	G	Controls	<24	Both	799	22.0/49.7/28.3
				Cases	>26	Both	1,247	22.7/50.7/26.5	0.630	1.04 (0.88–1.24)	0.744	1.05 (0.80–1.37)	0.642	1.07 (0.80–1.43)
					>28	Both	361	23.4/52.4/24.2	0.347	1.12 (0.88–1.42)	0.160	1.31 (0.90–1.92)	0.917	1.02 (0.69–1.51)
					>29	Both	111	25.5/53.6/20.9	0.272	1.21 (0.86–1.71)	0.116	1.58 (0.88–2.81)	0.831	1.06 (0.60–1.88)
					>30	Both	30	30.0/53.3/16.7	0.474	1.23 (0.70–2.14)	0.248	1.79 (0.64–5.01)	0.953	1.03 (0.41–2.55)
rs644242	31,812,801	G>T	G	Controls	<24	Both	799	78.8/19.5/1.7
				Cases	>26	Both	1,247	81.3/17.2/1.5	0.475	1.11 (0.84–1.45)	0.156	2.05 (0.77–5.42)	0.717	1.06 (0.78–1.44)
					>28	Both	361	84.0/14.0/2.0	0.119	1.35 (0.93–2.00)	0.167	2.40 (0.68–8.39)	0.189	1.34 (0.86–2.10)
					>29	Both	111	86.4/11.8/1.8	0.123	1.56 (0.87–2.78)	0.486	1.77 (0.33–9.35)	0.113	1.72 (0.86–3.46)
					>30	Both	30	86.7/10.0/3.3	0.363	1.52 (0.59–3.85)	0.939	1.09 (0.12–9.98)	0.269	1.87 (0.58–6.04)
rs3026390	31,813,509	A>G	G	Controls	<24	Both	799	21.8/49.8/28.4
				Cases	>26	Both	1,247	22.8/50.8/26.4	0.619	1.04 (0.88–1.24)	0.728	1.05 (0.80–1.38)	0.641	1.07 (0.80–1.43)
					>28	Both	361	23.3/52.8/23.9	0.326	1.13 (0.89–1.43)	0.135	1.34 (0.91–1.96)	0.937	1.02 (0.69–1.50)
					>29	Both	111	25.2/54.1/20.7	0.273	1.21 (0.86–1.71)	0.108	1.59 (0.89–2.84)	0.863	1.05 (0.59–1.86)
					>30	Both	30	30.0/53.3/16.7	0.477	1.22 (0.70–2.14)	0.251	1.78 (0.63–5.00)	0.953	1.03 (0.41–2.55)
rs667773	31,815,362	C>T	C	Controls	<24	Both	799	78.8/19.4/1.8
				Cases	>26	Both	1,247	81.4/17.1/1.5	0.417	1.12 (0.85–1.47)	0.146	2.06 (0.79–5.41)	0.647	1.07 (0.79–1.46)
					>28	Both	361	84.6/13.5/2.0	0.083	1.39 (0.95–2.04)	0.164	2.38 (0.69–8.22)	0.130	1.41 (0.90–2.19)
					>29	Both	111	86.4/11.8/1.8	0.111	1.56 (0.88–2.78)	0.473	1.79 (0.34–9.42)	0.102	1.75 (0.87–3.51)
					>30	Both	30	86.7/10.0/3.3	0.349	1.52 (0.60–3.85)	0.930	1.10 (0.12–10.05)	0.258	1.90 (0.59–6.12)

Notes:

a Multiple inheritance models were applied in analysis of genotype data to assess each risk allele: additive (R/R vs R/nR vs nR/nR), dominant (R/R + R/nR vs nR/nR), and recessive (R/R vs R/nR + nR/nR) models were assessed. P-values and ORs were adjusted for age and sex.

Abbreviations: 1, major allele; 2, minor allele; AL, axial length; CI, confidence interval; nR, non-risk allele; OR, odds ratio; PAX6, paired box 6; R, risk allele; SNPs, single nucleotide polymorphisms.