‘The Thousand Polish Genomes Project’ - a national database of Polish variant allele frequencies

Abstract

Although Slavic populations account for over 3.5% of world inhabitants, no centralized, open source reference database of genetic variation of any Slavic population exists to date. Such data are crucial for either biomedical research and genetic counseling and are essential for archeological and historical studies. Polish population, homogenous and sedentary in its nature but influenced by many migrations of the past, is unique and could serve as a good genetic reference for middle European Slavic nations.The aim of the present study was to describe first results of analyses of a newly created national database of Polish genomic variant allele frequencies. Never before has any study on the whole genomes of Polish population been conducted on such a large number of individuals (1,079).A wide spectrum of genomic variation was identified and genotyped, such as small and structural variants, runs of homozygosity, mitochondrial haplogroups and Mendelian inconsistencies. The allele frequencies were calculated for 943 unrelated individuals and released publicly as The Thousand Polish Genomes database. A precise detection and characterisation of rare variants enriched in the Polish population allowed to confirm the allele frequencies for known pathogenic variants in diseases, such as Smith-Lemli-Opitz syndrome (SLOS) or Nijmegen breakage syndrome (NBS). Additionally, the analysis of OMIM AR genes led to the identification of 22 genes with significantly different cumulative allele frequencies in the Polish (POL) vs European NFE population. We hope that The Thousand Polish Genomes database will contribute to the worldwide genomic data resources for researchers and clinicians.

National Genome Initiatives in Europe and the United Kingdom in the Era of Whole-Genome Sequencing: A Comprehensive Review

“…Pilot results from a cohort of 1079 individuals showed total of 31.24 million SNPs and 5.63 million small indels. On average, 4.48 million small variants per individual were found, of which 16,473 were private variants [ 61 ].…”

Oligogenic risk model for Gilles de la Tourette syndrome reveals a genetic continuum of tic disorders

“…Uniquely, our study involved patients with severe GTS, meaning patients with troublesome tics that persisted into adulthood. To further augment the analyses we used simulated samples based on a database of allele frequencies of the general Polish population (Kaja et al 2021). The presented oligogenic risk model was developed in two steps and is based on variants in and in the vicinity of ten genes; CHADL, DRD2, MAOA, PCDH10, HTR2A, SLITRK5, SORCS3, KCNQ5, CDH9, and CHD8.…”

“…To ensure the robustness of the results two additional control groups were used. In the discovery phase we included synthetic controls based on a database of allele frequencies of the local (Polish) population (Kaja et al 2021). Synthetic samples were genotyped with MAF of each of the variants in the database as probabilities of assignment of a given allele.…”

“…In the first part of the analyses GTS patients outside families (n = 37) were compared with synthetic controls based on a database of WGS allele frequencies in the Polish population (Kaja et al 2021). To ensure robustness of the results 25 comparisons were run at this step (GTS patients vs each one of 25 groups sampled from 2500 synthetic controls).…”

Genetic diversity in Kashubs: the regional increase in the frequency of several disease-causing variants

“…This low ethnic diversity in the present-day population of Poland is reflected by its genetic homogeneity. It is supported by numerous studies: on blood group systems [Gronkiewicz 1996], human leukocyte antigen (HLA) haplotypes [Schmidt et al 2013], the Y-chromosome lineages [Płoski et al 2002;Rębała et al 2013], major mtDNA haplogroups [Malyarchuk et al 2002;Grzybowski et al 2007;Mielnik-Sikorska et al 2013;Jarczak et al 2019], the forensic short tandem repeat (STR) markers [Sołtyszewski et al 2008], and recently by whole-genome sequencing (WGS) data [Kaja et al 2021].…”