Role of individual, peer and family factors in the use of cannabis and other illicit drugs: A longitudinal analysis among Finnish adolescent twins

Background: Although use of illicit drugs shows varying degree of heritability, the influence of shared and unique environmental factors predominate among adolescents. We explored factors predicting use of cannabis and other illicit drugs among Finnish adolescent twins. Methods: We used longitudinal data from the FinnTwin12-17 study with baseline at age 11-12 and follow-up at ages 14 and 171/2, including 4138 individuals. The outcome was self-reported ever use of cannabis or other illicit drugs at age 171/2. The potential predictors were measures reported by the twins, their parents or teachers. As individual factors we tested smoking, alcohol use, behavioral and emotional problems; as peer factors: number of smoking friends and acquaintances with drug experience; as family factors: parental substance use, socio-economic status and pre-natal exposure to nicotine. We used logistic regression models, controlling for twinship, age and sex, to compute odds ratios (OR) for each potential predictor. To adjust for within-family confounds, we conducted conditional logistic regressions among 246 twin pairs discordant for drug use. Results: 13.5% of subjects had initiated use of cannabis or other illicit drugs by age of 171/2. When adjusted for within-family confounds, smoking, drinking, and aggressiveness, as well as smoking and drug use among peers predicted use of illicit drugs. In the final regression model, the significant predictors were female sex, early smoking onset, drinking to intox

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation