Discussion
amisulpride-induced weight gain, weight gain
REGRESSION, MINOR, REGRESSIONS
We observed a statistically significant association between the rs17782313 polymorphism and absolute weight gain and absolute BMI gain after 8 weeks of antipsychotic treatment in the amisulpride subpopulation when comparing carriers of the C allele with TT carriers. The same direction of effect could be seen in the entire population and the olanzapine group, though it failed to reach conventional levels of statistical significance. The analysis indicates that the C allele might lead to a higher weight and BMI gain under SGA treatment.TC carriers showed a higher baseline body weight and BMI than TT carriers in all populations, as previously shown in the GWAS (Loos et al. Patients in the olanzapine medication group gained a mean ± SD body weight of 2.4±4.2 kg within 8 weeks. A meta-analysis from Allison et al. (In first episode patients, the rs17782313 was significantly associated with weight gain and relative weight gain (compared to baseline) after 8 weeks, even after comparing for multiple corrections, though due to the low minor allele frequency only one individual was homozygous for the C-allele, and that patient happened to experience a multiple times larger increase in body weight. Czerwensky et al. (Patients homozygous for the rs17782313 C allele gained both more absolute and more relative weight than those heterozygous for the C allele or TT carriers in all three medication groups after 2 weeks as well as after 8 weeks of antipsychotic treatment. Despite these differences not reaching significant levels, a correction for known confounders in stepwise multiple linear regressions showed significant As the increased weight gain is attributed to the C allele, the comparison of subjects homozygous or heterozygous for the C allele to those homozygous for the T allele showed a tendency in the whole population and in the amisulpride subpopulation of a significant difference for the entire duration of the trial but not after 2 weeks. Such short intervals might be simply not long enough for the genetic influence on AIWG to be seen. Czerwensky et al. (When comparing the two antipsychotic substances, in patients only treated with amisulpride, the relative weight gain of the CC allele carriers after the full 8 weeks of treatment was 4.5 times higher and of the TC allele carriers 2.3 times higher than that of TT carriers, yet in patients only treated with olanzapine, it was 2.0 times higher in CC carriers respectively 1.5 times higher in heterozygous patients than in those homozygous for the T allele. Furthermore, in the stepwise multiple linear regressions, the influence of the We decided to perform Holm’s procedure to correct for multiple comparisons to evaluate robustness of our statistical findings. The MC4R genotype remained significantly associated with weight gain after 8 weeks in first episode patients (TT vs TC vs CC) and as a factor in multiple linear regression in ‘completers’ of the trial. Therefore, our statistical findings should be interpreted carefully. However, we believe that exploratory approaches do not provide strict evidence for certain genetic effects in the first place, but they help investigate possible associations and are necessary for later more rigorous studies. Moreover, even results that have no significant association with a proposed effect but show a tendency should be reported as they would otherwise lead to publication bias.Some limitations of this study must be mentioned. First, although there were only two different SGAs given and the number of subjects treated with each one is therefore relatively large, the overall study population consisted of only 252 patients for the first 2 weeks and 212 individuals for the entire 8 weeks and is smaller than in the previous analyses (Chowdhury et al. In this study, we report a significant association of amisulpride-induced weight gain after 8 weeks of treatment and the rs17782313 C allele, a polymorphism located in the promoter region of 