ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.
ANKK1, TTC12, and NCAM1 polymorphisms and heroin dependence: importance of considering drug exposure.
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ANKK1，TTC12和NCAM1多态性和海洛因依赖性：考虑药物暴露的重要性。
DOI：
10.1001/jamapsychiatry.2013.282
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发表时间：
2013-03
期刊：
影响因子：
25.8
通讯作者：
Montgomery, Grant W.
中科院分区：
文献类型：
--
作者：
Nelson, Elliot C.;Lynskey, Michael T.;Heath, Andrew C.;Wray, Naomi;Agrawal, Arpana;Shand, Fiona L.;Henders, Anjali K.;Wallace, Leanne;Todorov, Alexandre A.;Schrage, Andrew J.;Saccone, Nancy L.;Madden, Pamela A. F.;Degenhardt, Louisa;Martin, Nicholas G.;Montgomery, Grant W.
遗传对阿片类药物依赖的影响是众所周知的；事实证明，识别相关基因具有挑战性。为了检查 1430 个候选基因单核苷酸多态性 (SNP) 与海洛因依赖的关联，本文仅报告 11 号染色体基因簇（NCAM1、TTC12、ANKK1、DRD2）中的 71 个 SNP，其中包括观察到的最强关联。病例对照遗传关联研究，包括两个对照组（缺乏既定的最佳对照组）。半结构化精神病学访谈从阿片类药物替代治疗 (ORT) 诊所确定的澳大利亚病例 (N=1459)、从阿片类药物替代治疗诊所附近的经济贫困地区确定的社区对照 (N=531)，以及从双胞胎和家庭样本中选择的不依赖酒精或非法药物的不相关澳大利亚双胞胎登记处 (ATR) 对照 (N=1495)。终生海洛因依赖 将病例与澳大利亚双胞胎登记对照进行比较，发现所有 11 号染色体簇 SNP 关联的证据极少 (p≥.01)；与邻域对照的类似比较揭示了更大的差异（p≥1.8 × 10−4）。将病例 (N=1459) 与不依赖非法药物的邻里对照亚组 (N=340) 进行比较，发现三个 SNP 显着相关（针对多重测试进行校正）： ANKK1 SNP rs877138 [最强相关；比值比 1.59； 95% CI (1.32–1.92)； p=9.7 × 10−7]，ANKK1 SNP rs4938013 和 TTC12 SNP rs7130431。在比较非法药物依赖（N = 191）和非依赖（N = 340）邻里控制时观察到类似的关联模式，表明责任可能延伸到非阿片类非法药物依赖。与两个 SNP rs877138 和 rs4492854（位于 NCAM1）相关的总体海洛因依赖风险变化超过 4 倍（对于风险相关线性趋势，p = 2.74 × 10−9）。我们的结果进一步证明 11 号染色体基因簇 SNP 与物质依赖之间的关联，包括扩大非法药物依赖的责任。我们的研究结果强调了在选择对照组进行非法药物依赖遗传研究时考虑药物暴露史的必要性。
The genetic contribution to liability for opioid dependence is well-established; identification of the responsible genes has proved challenging. To examine association of 1430 candidate gene single-nucleotide polymorphisms (SNPs) with heroin dependence, reporting here only the 71 SNPs in the chromosome 11 gene cluster (NCAM1, TTC12, ANKK1, DRD2) that include the strongest observed associations. Case-control genetic association study that included two control groups (lacking an established optimal control group). Semi-structured psychiatric interviews Australian cases (N=1459) ascertained from opioid replacement therapy (ORT) clinics, neighborhood controls (N=531) ascertained from economically disadvantaged areas near opioid replacement therapy clinics, and unrelated Australian Twin Registry (ATR) controls (N=1495) not dependent on alcohol or illicit drugs selected from a twin and family sample. Lifetime heroin dependence Comparison of cases with Australian Twin Registry controls found minimal evidence of association for all chromosome 11 cluster SNPs (p≥.01); a similar comparison to neighborhood controls revealed greater differences (p≥1.8 × 10−4). Comparing cases (N=1459) with the subgroup of neighborhood controls not dependent on illicit drugs (N=340), three SNPs were significantly associated (correcting for multiple testing): ANKK1 SNP rs877138 [most strongly associated; odds ratio 1.59; 95%CI (1.32–1.92); p=9.7 × 10−7], ANKK1 SNP rs4938013 and TTC12 SNP rs7130431. A similar pattern of association was observed when comparing illicit drug-dependent (N=191) and non-dependent (N=340) neighborhood controls, suggesting that liability likely extends to non-opioid illicit drug dependence. Aggregate heroin dependence risk associated with two SNPs, rs877138 and rs4492854 (located in NCAM1), varied more than 4-fold (p= 2.74 × 10−9 for the risk-associated linear trend). Our results provide further evidence of association for chromosome 11 gene cluster SNPs with substance dependence, including extension of liability to illicit drug dependence. Our findings highlight the necessity of considering drug exposure history when selecting control groups for genetic investigations of illicit drug dependence.
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影响因子：
30.8
作者：
de Bakker, PIW;Yelensky, R;Altshuler, D
通讯作者：
Altshuler, D
影响因子：
3.7
作者：
Garrido, E.;Palomo, T.;Hoenicka, J.
通讯作者：
Hoenicka, J.
DOI：
10.1111/j.1530-0277.2010.01156.x
发表时间：
2010-05
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Edenberg HJ;Koller DL;Xuei X;Wetherill L;McClintick JN;Almasy L;Bierut LJ;Bucholz KK;Goate A;Aliev F;Dick D;Hesselbrock V;Hinrichs A;Kramer J;Kuperman S;Nurnberger JI Jr;Rice JP;Schuckit MA;Taylor R;Todd Webb B;Tischfield JA;Porjesz B;Foroud T
通讯作者：
Foroud T
影响因子：
10.5
作者：
Kendler, KS;Karkowski, LM;Neale, MC
通讯作者：
Neale, MC
影响因子：
7.6
作者：
Huang, Weihua;Payne, Thomas J.;Li, Ming D.
通讯作者：
Li, Ming D.