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Background: The Mental Health Continuum-Short Form (MHC-SF) is a measure of positive mental health and flourishing, which is widely used in several countries but has not yet been validated in Denmark. This study aimed to examine its qualitative and quantitative properties in a Danish population sample and compare scores with Canada and the Netherlands., Methods: Three thousand five hundred eight participants aged 16-95 filled out an electronic survey. Both the unidimensional and multidimensional aspects of the Danish MHC-SF were studied through bifactor modelling. Cognitive interviews examined face validity and usability., Results: The general score of the Danish MHC-SF was reliable for computing unit-weighted composite scores, as well as using a bifactor model to compute general factor scores or measurement models in an SEM context. Nonetheless, subscale scores were unreliable, explaining very low variance beyond that explained by the general factor. The participants of the qualitative interviews observed problems with wording and content of the items, especially from the social subscale. The general score correlated with other scales as expected. We found substantial variation in flourishing prevalence rates between the three cultural settings., Conclusions: The Danish MHC-SF produced reliable general scores of well-being. Most of the issues observed regarding the subscale scores have been shown in previous research in other contexts. The further analysis of indices of the bifactor model and the inclusion of qualitative interviews allowed for a better understanding of the possible sources of problems with the questionnaire's subscales. The use of subscales, the substantive understanding of the general score, as well as the operationalization of the state of flourishing, require further study.

Although genome-wide association studies (GWAS) have identified many common variants associated with complex traits, low-frequency and rare variants have not been interrogated in a comprehensive manner. Imputation from dense reference panels, such as the 1000 Genomes Project (1000G), enables testing of ungenotyped variants for association. Here we present the results of imputation using a large, new population-specific panel: the Genome of The Netherlands (GoNL). We benchmarked the performance of the 1000G and GoNL reference sets by comparing imputation genotypes with 'true' genotypes typed on ImmunoChip in three European populations (Dutch, British, and Italian). GoNL showed significant improvement in the imputation quality for rare variants (MAF 0.05-0.5%) compared with 1000G. In Dutch samples, the mean observed Pearson correlation, r(2), increased from 0.61 to 0.71. We also saw improved imputation accuracy for other European populations (in the British samples, r(2) improved from 0.58 to 0.65, and in the Italians from 0.43 to 0.47). A combined reference set comprising 1000G and GoNL improved the imputation of rare variants even further. The Italian samples benefitted the most from this combined reference (the mean r(2) increased from 0.47 to 0.50). We conclude that the creation of a large population-specific reference is advantageous for imputing rare variants and that a combined reference panel across multiple populations yields the best imputation results.