Imputation servers offer the exclusive possibility to harness the largest public reference panelswhich have been shown to deliver very high precision in the imputation of European genomes. Manystudies have nonetheless stressed the importance of ‘study specific panels’ (SSPs) as an alternativeand have shown the benefits of combining public reference panels with SSPs. But such combinedapproaches are not attainable when using external imputation servers. To investigate how toconfront this challenge, we imputed 550 French individuals using either the University of Michiganimputation server with the Haplotype Reference Consortium (HRC) panel or an in‑house SSP of 850whole‑genome sequenced French individuals. With approximate geo‑localization of both our targetand SSP individuals we are able to pinpoint different scenarios where SSP‑based imputation wouldbe preferred over server‑based imputation or vice‑versa. This is achieved by showing to a high degreeof resolution the importance of the proximity of the reference panel to target individuals; with afocus on the clear added value of SSPs for estimating haplotype phase and for the imputation of rarevariants (minor allele‑frequency below 0.01). Such benefits were most evident for individuals fromthe same geographical regions in France as the SSP individuals. Overall, only 42.3% of all 125,442variants evaluated were better imputed with an SSP from France compared to an external referencepanel, however this rises to 58.1% for individuals from geographic regions well covered by the SSP.By investigating haplotype sharing and population fine‑structure in France, we show the importanceof including SSP haplotypes for imputation but also that they should ideally be combined with largepublic panels. In the absence of the unattainable results from a combined panel of the HRC and ourFrench SSP, we put forward a pragmatic solution where server‑based and SSP‑based imputationoutcomes can be combined based on comparing posterior genotype probabilities. We show that suchan approach can give a level of imputation accuracy in excess of what could be achieved with eitherstrategy alone. The results presented provide detailed insights into the accuracy of imputation thatshould be expected from different strategies for European populations.< Leer menos