Genetic analysis of DNA methylation and gene expression levels in whole blood of healthy human subjects

BMC Genomics

Table 3 Top results LEO analysis, Results for top SNPs

Gene symbol	M&E	CGI	LEO model	LEO score	P-value	Top SNP	Chr	Bp	Full name
*BTN3A2*	-	Outside	S → M → E	6.90	0.15	rs2093169	6	26,603,078	butyrophilin, subfamily 3, member A2
HP	-	Outside	S → M → E	4.24	0.82	rs8044555	16	70,710,256	haptoglobin
*CTSW*	-	Outside	S → M → E	2.73	0.13	rs11227306	11	65,335,248	cathepsin W
*NAPRT1*	-	Shore	S → M → E	2.69	0.11	rs4874159	8	144,742,093	nicotinate phosphoribosyltransferase domain containing 1
*PHACS*	-	Shore	S → M → E	1.50	2.9e-03	rs4755227	11	44,078,659	1-aminocyclopropane-1-carboxylate synthase homolog
*PNMA3*	+	Shore	S → M → E	1.36	0.16	rs6627737	X	151,971,610	nicotinate phosphoribosyltransferase domain containing 1
*CDC16*	-	Island	S → M → E	1.09	0.01	rs11147317	13	113,957,498	cell division cycle 16 homolog (S. cerevisiae)
*HRASLS3*	-	Shore	S → E → M	2.42	7.2e-04	rs2030731	11	63,130,224	phospholipase A2, group XVI
*TACSTD2*	-	Island	S → E → M	2.08	9.5e-03	rs11207272	1	58,846,018	tumor-associated calcium signal transducer 2
*SRXN1*	-	Shore	S → E → M	1.87	5.4e-03	rs6076864	20	569,825	sulfiredoxin 1 homolog (S. cerevisiae)
*C21orf56*	-	Outside	S → E → M	1.30	2.8e-03	rs8133866	21	46,423,604	chromosome 21 open reading frame 56
*BTN3A2*	-	Outside	S → E → M	1.14	6.4e-05	rs12199613	6	26,475,197	butyrophilin, subfamily 3, member A2
*WBSCR27*	-	Shore	S → E → M	0.95	8.6e-04	rs11763011	7	72,922,084	Williams Beuren syndrome chromosome region 27
*GSTM3*	-	Island	S → E → M	0.88	1.4e-03	rs11807	1	110,062,265	glutathione S-transferase mu 3 (brain)

This table contains top probes resulting from causality analysis (LEO scores > 0.8). The top seven genes fit the causal scenario SNP → Methylation → Expression (S→M→E), while the bottom seven genes fit the reverse model in which DNA methylation is regulated by gene expression that is under genetic control (S→E→M). The Gene Symbol is given in the first column. The second column indicates whether the methylation and expression levels are associated negatively (−) or positively (+). The third column indicates whether the methylation probe is located in a CpG island (CGI), in the shore, or outside both. The columns “LEO model”, “LEO score” and “P-value” indicate which causal model fits best with the corresponding LEO score and P-value. This model fitting p-value is calculated using the model chi-square statistic statistic. The chi-square statistic tests the null hypothesis that the model is correct, thus a p-value > 0.01 indicates good fit. The next column indicates the SNP most significantly associated. The last three columns contain chromosome number and base pair location (NCBI build 36) of the SNP and full name of the gene.

ISSN: 1471-2164