Agrawal Arpana, Pergadia Michele L, Saccone Scott F, Lynskey Michael T, Wang Jen C, Martin Nicholas G, Statham Dixie, Henders Anjali, Campbell Megan, Garcia Robertino, Broms Ulla, Todd Richard D, Goate Alison M, Rice John, Kaprio Jaakko, Heath Andrew C, Montgomery Grant W, Madden Pamela A F
Department of Psychiatry, Washington University School of Medicine, 660 S Euclid Ave, Campus Box 8134, St Louis, MO 63110, USA.
Arch Gen Psychiatry. 2008 Jun;65(6):713-21. doi: 10.1001/archpsyc.65.6.713.
Despite accumulating evidence that there is a genetic basis for cannabis use disorders (ie, abuse and dependence), few studies have identified genomic regions that may harbor biological risk and protective factors.
To conduct autosomal linkage analyses that identify genomic regions that may harbor genes conferring a vulnerability to cannabis use disorders.
In 289 Australian families who participated in the Nicotine Addiction Genetics Project, 423 autosomal markers were genotyped. Families were ascertained for heavy cigarette smoking. Linkage was conducted for DSM-IV cannabis dependence and for a novel factor score representing problems with cannabis use, including occurrence of 3 of 4 abuse criteria (excluding legal problems) and 6 DSM-IV dependence criteria.
A maximum logarithm of odds (LOD) of 3.36 was noted for the cannabis problems factor score on chromosome arm 1p. An LOD of 2.2 was noted on chromosome 4 in the region of the gamma-aminobutyric acid type A gene cluster, including GABRA2, which has been implicated in drug use disorders. For DSM-IV cannabis dependence, a modest LOD score on chromosome 6 (1.42) near cannabinoid receptor 1 (CNR1) was identified. In addition, support for an elevation on chromosome 3, identified in prior independent studies, was noted for the factor score and cannabis dependence (LOD, 1.4).
Genes such as ELTD1 on chromosome 1, in addition to genes on chromosomes 4 (eg, GABRA2) and 6 (eg, CNR1), may be associated with the genetic risk for cannabis use disorders. We introduce a novel quantitative phenotype, a cannabis problems factor score composed of DSM-IV abuse and dependence criteria, that may be useful for future linkage and association studies.
尽管越来越多的证据表明大麻使用障碍（即滥用和依赖）存在遗传基础，但很少有研究确定可能包含生物学风险和保护因素的基因组区域。
进行常染色体连锁分析，以确定可能包含使个体易患大麻使用障碍的基因的基因组区域。
在参与尼古丁成瘾遗传学项目的289个澳大利亚家庭中，对423个常染色体标记进行了基因分型。这些家庭因重度吸烟而被确定。对《精神疾病诊断与统计手册》第四版（DSM-IV）中的大麻依赖以及一个代表大麻使用问题的新因素评分进行了连锁分析，该评分包括4项滥用标准中的3项（不包括法律问题）和6项DSM-IV依赖标准。
在1号染色体臂上，大麻问题因素评分的最大对数优势比（LOD）为3.36。在4号染色体上，γ-氨基丁酸A型基因簇区域（包括与药物使用障碍有关的GABRA2）的LOD为2.2。对于DSM-IV大麻依赖，在大麻素受体1（CNR1）附近的6号染色体上确定了一个适度的LOD评分（1.42）。此外，对于因素评分和大麻依赖，在先前独立研究中确定的3号染色体上的升高得到了支持（LOD，1.4）。
除了4号染色体（如GABRA2）和6号染色体（如CNR1）上的基因外，1号染色体上的ELTD1等基因可能与大麻使用障碍的遗传风险相关。我们引入了一种新的定量表型，即由DSM-IV滥用和依赖标准组成的大麻问题因素评分，这可能对未来的连锁和关联研究有用。
