Biological Gene number Partial related methylated genes function Adhesion 580 Sox-2, Shh, Itpkb, Pkd1, Reln, Ptk2b, Nck2
, Ass1 Lphn1, Cdh9, Epdr1, Myf5, Pdpn, Has2, Fgfrl1, Fer Secretion 553 Lphn1, Pim3, Fst, Pim3, Pcsk6, Lax1, Sct, Sytl3 Plcd1, Ykt6, Jak1, Stat2, Myc, Csf2, Lifr, Sos1 Proliferation 787 Dixdc1, Lrp6, Edn3, Nkx2, Cyr61, Src, Sox8, Stk4 Ephb1, Sstr3, Rrm2, Tcf3, Grn, Rhoa, Apc, Nox4, Strn Neuronal 473 Bhlhb9, Cckar, Fzd2, Thy1, Pbx3, regeneration Otx2, Lhx8, Btg2 Klhl1, Dlg2, Pak1, Wnt3, Mif, Tctn1, Evl, Ext1, Als2 Axonal 215 Ifrd1, c-Jun, Bcl2, Tnn, Mbp, Slit3, regeneration Ist1, Drgx, Thy1 Unc5c, Ntrk2, Isl1, Ptk2, Dscam, Atl1, Dnm2, Cxcl12 Figure 3: (a) The distribution of differentially methylated regions (DMRs) peaks in different components of genome.
In our analysis, we find a genome-wide significant association of NCK2 gene on chromosome 2 with opiates dependence in African-origin men at both the SNP and gene levels.
Table 2 summarizes the top four significant SNPs (with P < 1.0 x [10.sup.-4]) in gene NCK2 on chromosome 2 (2q12) for opiates dependence in African-origin men.
Specifically, we included 39 SNPs in NCK2. The P values from the gene-NCK2-based tests that were obtained through the standard allelic test and logistic regression are 3.12 x [10.sup.-10] and 2.70 x [10.sup.-6], respectively.
We also examined association of haplotypes with opiate addiction in NCK2 region.
In Table 5, we also presented the association results for NCK2 and comorbidity of substance dependence.
The NCK2 gene that contains SNP rs2377339 also achieved the genome-wide significance for opiates dependence at the gene level.
NCK2, a member of NCK family of adaptor proteins, is reported to be associated with tyrosine-phosphorylated growth factor receptors of their cellular substrate .
This approach, which is a realistic depiction of substance dependence, confirmed that a novel susceptibility gene, NCK2 is significantly associated with substance dependence in African-origin men.
Ota et al., "Microsatellite analysis of the GLC1B locus on chromosome 2 points to NCK2 as a new candidate gene for normal tension glaucoma," British Journal of Ophthalmology, vol.