Novel Associations of Nonstructural Loci with Paraoxonase Activity

Table 2

Summary of Significant and Suggestive Associations. SNP associations varied among substrates with overlap only at rs1078701 on chromosome 4. For each SNP, the chromosomal location, proportion of variation in PON1 activity explained, measured genotype test 𝑃-value, and minor allele frequency are listed. Shoulder SNPs are SNPs ranking in the top 5% of associations located within 500 kb of the significantly associated SNP. Genes identified by SUSPECTS are within 7.5 Mb of the candidate SNP and have a similarity score greater than 15. Bolded genes are discussed in the texts as the most likely contributors to PON1 activity based on known function, however, other genes may have unknown functions important in the regulation of PON1. The two associated SNPs on chromosome 3 are in perfect linkage disequilibrium and explain 2.7% of the variation in PON1-lact cumulatively.

Substrate	SNP	Chr	Position	Variation Explained	MG p	MAF	Shoulder SNPs	SUSPECTS Genes
para	rs12083993	1	64,691,396	1.2%	1.8𝐸−07	0.3%	34	ALG6, ANGPTL3, CYP2J2, IL12RB2, INSL5, LEPROT, OMA1, PTGER3
lact	rs13322362	3	76,613,497	2.7%	4.8𝐸−07	5.4%	6	PROK2, ROBO1, ROBO2
lact	rs11915977	3	76,613,530		4.8𝐸−07	5.5%
para				1.8%	4.7𝐸−09		32
aryl	rs1078701	4	8,241,119	2.8%	3.0𝐸−08	2.2%	19	ADD1, CPZ, DGKQ, FGFBP1, FGFR3, FGFRL1, HGFAC, HS3ST1, LRPAP1, MXD4
lact				2.3%	3.8𝐸−07		15
aryl	rs2299262	7	94,787,864	2.8%	1.3𝐸−07	43.9%	24	PON1
lact	rs7225624	17	47,811,373	2.9%	4.7𝐸−09	0.3%	4	ABCD4, ADAM11, DGKE, GRN, HOXB2, NGFR, NMT1, OSBPL7, PLCD3, PCTP, SCPEP1, SLC35B1