Association of ENPP1gene polymorphisms with hand osteoarthritis in a Chuvasha population

Table 3 Tests of association between ENPP1 polymorphisms and osteoarthritis (OA) of hand joints

Marker	Allele/haplotype	Freq.	P values of TDT			Combined P values for 3 tests^a		Bonferroni correction		n inf.	n test	Pedigree-based disequilibrium test
			FBAT	QTDT^b	EOT	A	B	A	B			P	Δ (years)
M06NR1A	4F^c	0.27	0.0001	1.0e-5	0.0009	<1.0e-6	<5.0e-5	<4.0e-6	<2.0e-5	84	4	0.0002	-3.5
K173Q	1	0.11	0.0129	0.0347	0.0403	0.0020	0.0104	0.0020	0.0104	48	1	0.0196	1.9
_XXX^d	_221	0.66	0.0147	0.0174	0.0043	0.0002	0.0033	0.0006	0.0099	88	3	0.3430	-1.3
_XXX	_211	0.10	0.0148	0.0373	0.0096	0.0007	0.0074	0.0021	0.0220	39	3	0.0110	2.3
_XX_	_22_	0.67	0.0046	0.0050	0.0030	1.8e-5	0.0006	0.0001	0.0018	89	3	0.1827	-1.7
_XX_	_21_	0.10	0.0114	0.0378	0.0091	0.0005	0.0062	0.0016	0.0185	40	3	0.0114	2.3
__XX	__11	0.12	0.0426	0.0509	0.0426	0.0074	0.0177	0.0147	0.0351	47	2	0.0278	2.1
__XX	__21	0.85	0.0362	0.0515	0.0576	0.0082	0.0205	0.0164	0.0406	58	2	0.1574	-1.6

Osteoarthritis scores were measured by the Kellgren–Lawrence method [19]. K–L scores of 28 joints on both hands, which were used as primary phenotype. The primary phenotype was subjected to principal component analysis resulting in first factor scores (FS1-OAs). After being adjusted for age, FS1-OA was used as a quantitative trait for the association tests. ^aCombined P value using χ² (A) and simulated three-dimensional null distribution (B). ^bColumn presents orthogonal test, which uses parent trait values as covariates. ^cF is an artificial 'allele' combining all rare alleles but not the three most frequent ones. ^dXXXX is the haplotype of the four SNPs (rs1800949, rs858342, K173Q, and R774C). The minor allele frequencies of the four individual SNPs in the study population are 0.24 for the T-allele (2) of rs1800949, 0.21 for the G-allele (1) of rs858342, 0.11 for the C-allele (1) of K173Q, and 0.03 for the T-allele (2) of R774C. Δ, mean difference between the allele carriers and other individuals in age at onset of the disorder; EOT = extreme offspring design t-test; FBAT, family-based association test; Freq., frequency; n inf., number of informative families for TDT in the sample; n test, number of tests performed for the marker (alleles with n inf. >40); QTDT, quantitative transmission disequilibrium test; TDT, transmission disequilibrium test.

ISSN: 1478-6362