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LATVIAN

BIOMEDICAL

RESEARCH AND STUDY CENTRE


RESEARCH AND EDUCATION IN BIOMEDICINE FROM GENES TO HUMAN

Project Title: “An integrated population based Latvian genome reference and its applicability to personal risk estimation for metabolic traits”

Funding: European Regional Development Fund (ERDF), Measure 1.1.1.1 “Support for applied research”

Project No.: 1.1.1.1/20/A/126

Period: 1 March 2021 – 30 November 2023

Project costs: 540 540.54 EUR

Principle Investigator: Dr. biol. Jānis Kloviņš

Cooperation partner: SIA “Latvia MGI Tech”

Project summary:

This project aims is to create the first Latvian genome variation reference and estimate the accurate, population-specific PRS for the metabolic disease using the national biobank, the Genome Database of Latvian Population (LGDB) resource establishing a functional framework for -omics based personalised prevention and treatment program in Latvia.

The aim of our project is to create the first Latvian genome variation reference and estimate the accurate, population-specific polygenic risk scores (PRS) for the metabolic disease using the national biobank the Genome Database of Latvian Population resource establishing a functional framework for -omics based personalised prevention and treatment program in Latvia. The project will have a great impact on the further development of genomics-based medicine in Latvia and resources created in the frame of this project will also be available for the whole research community. More specifically, we will target diabetes and produce validated optimal polygenic risk scores for this type 2 diabetes and other metabolic parameters and will use this information to search for novel biomarkers or possible patient subgroups that would benefit from the knowledge of their genetics.

Information published 01.03.2021.

Progress of the project:

1 March 2021 – 31 May 2021

In the first quarter of the project, cohort selection is performed using the resources of the Genome database of Latvian population, including individuals representing the general population, patients with type 2 diabetes within the OPTOMED cohort, patients with type 2 diabetes outside the OPTIMED cohort with additional longitudinal samples and MODY patients. The clinical parameters that will be obtained from the health data registries are selected in order to supplement the range of related data available in the Genome database of Latvian population. In addition, selection of DNA samples and quality control are performed for the preparation of the next generation of sequencing libraries.

Information published 31.05.2021.

Progress of the project:

1 June 2021 – 31 August 2021

Cohort selection was performed using the resources of the National Genome Database of Latvia. Using MGI next-generation sequencing technology, full genome sequences have been obtained for 236 samples collected from both healthy individuals and patients with type 2 diabetes. The quality control of the full genome sequencing data obtained in the first work package and the development of the analysis workflow have been started. Scientific literature is analyzed and various tools for primary data processing, identification of polymorphisms, insertions, deletions and structural variations are tested using HPC resources of Riga Technical University.

Information published 31.08.2021.

Progress of the project:

1 September 2021 – 30 November 2021

New samples are selected from the Genome Database of Latvian Population, DNA quality control and sample preparation for the next-generation sequencing with MGI DNA nano-bead-based technology and DNBSEQ-T10 × 4 equipment have been done. The development of data analysis pipelines using the HPC resources of Riga Technical University is still ongoing. For 236 samples we have obtained full genome sequencing data, successfully determined the structural variations, SNPs, insertions/deletions, performed the quality control of sequencing data and mapping.

Information published 30.11.2021.

Progress of the project:

1 December 2021 – 28 February 2022

Statistical analysis of 213 whole-genome sequencing data was completed, including mapping, joint variant calling, calling of single nucleotide variants, indels, structural variations, and mobile elements, annotation of the location and function of these variants, analysis of population structure, and combining with others whole-genome data sets, including 1000 Genome Project. An additional 600 whole-genome sequences were obtained from both healthy individuals and patients with type 2 diabetes and MODY using MGI next-generation sequencing technology. Quality control of this data and data analysis is performed. Testing of selected tools for PRS calculation and process optimization is underway.

Information published 28.02.2022.

Progress of the project:

1 March 2022 – 31 May 2022

During the reporting period, an analysis of whole-genome sequencing data of 684 samples has been performed using a previously developed workflow. Calling of single nucleotide variants, indels, structural variations and mobile elements, annotation of the location and function of these variants, analysis of population structure and merging with other whole-genome data sets have been performed. The imputation quality using the 1000 Genomes project panel has been compared with the combined panel, which additionally contains the whole-genome sequences of the Latvian population, and the results show significant improvements in the imputation quality. Polygenic risk scores in the cohort type 2 diabetes patients have been caluclated using previously published polygenic risk models.

Information published 31.05.2022.