ANKRD7 and CYTL1 are novel risk genes for alcohol drinking behavior / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Alcohol dependence (AD) is a complex disorder characterized by impaired control over drinking. It is determined by both genetic and environmental factors. The recent approach of genome-wide association study (GWAS) is a powerful tool for identifying complex disease-associated susceptibility alleles, however, a few GWASs have been conducted for AD, and their results are largely inconsistent. The present study aimed to screen the loci associated with alcohol-related phenotypes using GWAS technology.</p><p><b>METHODS</b>A genome-wide association study with the behavior of regular alcohol drinking and alcohol consumption was performed to identify susceptibility genes associated with AD, using the Affymetrix 500K SNP array in an initial sample consisting of 904 unrelated Caucasian subjects. Then, the initial results in GWAS were replicated in three independent samples: 1972 Caucasians in 593 nuclear families, 761 unrelated Caucasian subjects, and 2955 unrelated Chinese Hans.</p><p><b>RESULTS</b>Several genes were associated with the alcohol-related phenotypes at the genome-wide significance level, with the ankyrin repeat domain 7 gene (ANKRD7) showing the strongest statistical evidence for regular alcohol drinking and suggestive statistical evidence for alcohol consumption. In addition, certain haplotypes within the ANKRD7 and cytokine-like1 (CYTL1) genes were significantly associated with regular drinking behavior, such as one ANKRD7 block composed of the SNPs rs6466686-rs4295599-rs12531086 (P = 6.51 × 10(-8)). The association of alcohol consumption was successfully replicated with rs4295599 in ANKRD7 gene in independent Caucasian nuclear families and independent unrelated Chinese Hans, and with rs16836497 in CYTL1 gene in independent unrelated Caucasians. Meta-analyses based on both the GWAS and replication samples further supported the observed significant associations between the ANKRD7 or CYTL1 gene and alcohol consumption.</p><p><b>CONCLUSION</b>The evidence suggests that ANKRD7 and CYTL1 genes may play an important role in the variance in AD risk.</p>

Risk factors for methamphetamine-induced paranoia and latency of symptom onset in a Thai drug treatment cohort

Background: Methamphetamine (MA) produces a range of psychotic experiences, ranging from a sub-syndromal symptom to a full-scale psychosis. While the characteristics of and risk factors for MA-psychosis have been studied extensively, MA-induced paranoia (MIP) has received only limited attention.Methods: Demographic, diagnostic, and drug use variables were assessed in 96 experienced MA-users from a Thai drug treatment center using the Semi-Structured Assessment for Drug Dependence and Alcoholism (SSADDA) and the Methamphetamine Experienced Questionnaire (MEQ). Individuals with and without MIP were compared. Latency of the initial symptom onset was also examined.Results: Ninety-six subjects participated in the study including 44 (46%) endorsed MIP. Individuals with MIP were dependent on MA more severely than those without the trait (p=0.02). Subjects with MIP were also more likely to use solvents (p=0.03), be dependent on alcohol (p=0.048), and attempt suicide (p=0.04) than those without. Individuals with short latency to a first MIP episode (i.e., within two years of their first use of MA) did not differ from those with prolonged latency (≥ 3 years) with respect to MA use at symptom onset. However, they reported lower lifetime use (p=0.007), heaviest period use (p=0.008) and past-year MA use (p=0.04) than those with later onset.Conclusion: Severe dependence on MA, solvent use, alcohol dependence, and suicide attempts were associated with MIP. Though the vulnerability to MIP was associated with greater dependence severity as a group, those who experience MIP earlier in the course of their dependence reported less MA use than those in whom symptoms arose later. This suggests a subgroup of individuals that are intrinsically more vulnerable to the MA effects (e.g., habit forming and psychotic effects) and in whom MIP’s subjectively aversive effects may lead to reduced MIP use over the course of their MA dependence.