EBER variations in NPC cases (A) and healthy donors (B) from NPC non-endemic area in China.

<p>Numbers in the second top correspond to the nucleotide positions under which the B95-8 prototype nucleotide sequence is listed. Only nucleotides different from B95-8 are indicated. The changes in coding regions of EBER1 and EBER2 and non-coding region between EBER1 and EBER2 are separated by double lines and the positions are shown in the top. Different variants are noted to the left column, while the isolates showing identical sequences in each population group are listed by a representative isolate in the second column. The followed numbers in the parentheses denote the amount of the identical sequences from the same population group. The consensus sequence of each variant is shaded.</p

Genome-wide association meta-analysis of age at first cannabis use

Background and aims: Cannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants. Methods: A twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals. Results: The twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI) = 19–60%]. Shared and unique environmental factors explained 39% (95% CI = 20–56%) and 22% (95% CI = 16–29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P  0.8), with the strongest association at the intronic variant rs1574587 (P = 4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P = 1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant. Conclusion: Age at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders

Genome‐wide association meta‐analysis of age at first cannabis use

Background and aimsCannabis is one of the most commonly used substances among adolescents and young adults. Earlier age at cannabis initiation is linked to adverse life outcomes, including multi-substance use and dependence. This study estimated the heritability of age at first cannabis use and identified associations with genetic variants.MethodsA twin-based heritability analysis using 8055 twins from three cohorts was performed. We then carried out a genome-wide association meta-analysis of age at first cannabis use in a discovery sample of 24 953 individuals from nine European, North American and Australian cohorts, and a replication sample of 3735 individuals.ResultsThe twin-based heritability for age at first cannabis use was 38% [95% confidence interval (CI)&nbsp;=&nbsp;19-60%]. Shared and unique environmental factors explained 39% (95% CI&nbsp;=&nbsp;20-56%) and 22% (95% CI&nbsp;=&nbsp;16-29%). The genome-wide association meta-analysis identified five single nucleotide polymorphisms (SNPs) on chromosome 16 within the calcium-transporting ATPase gene (ATP2C2) at P&nbsp;&lt;&nbsp;5E-08. All five SNPs are in high linkage disequilibrium (LD) (r2 &nbsp;&gt;&nbsp;0.8), with the strongest association at the intronic variant rs1574587 (P&nbsp;=&nbsp;4.09E-09). Gene-based tests of association identified the ATP2C2 gene on 16q24.1 (P&nbsp;=&nbsp;1.33e-06). Although the five SNPs and ATP2C2 did not replicate, ATP2C2 has been associated with cocaine dependence in a previous study. ATP2B2, which is a member of the same calcium signalling pathway, has been associated previously with opioid dependence. SNP-based heritability for age at first cannabis use was non-significant.ConclusionAge at cannabis initiation appears to be moderately heritable in western countries, and individual differences in onset can be explained by separate but correlated genetic liabilities. The significant association between age of initiation and ATP2C2 is consistent with the role of calcium signalling mechanisms in substance use disorders