Saliva sample and isolation of genetic material
The genetic material used in Negen's gene tests, DNA, is obtained from a saliva sample, which is collected in a sampling tube provided for this purpose. The DNA contained in the saliva sample is isolated automatically. The concentration and purity of the isolated DNA is analysed and only samples that meet set quality standards are taken for post-processing. The DNA isolation and sample post-processing (i.e. genotyping) are conducted in a European laboratory specialising in the processing of genetic material.
Genotyping with microarray technology
In genotyping, the genetic information contained in the customer's DNA is determined from the samples using a DNA microarray technology. Negen uses the Illumina Infinium Global Screening Array (GSA) microarray in its genotyping. In genotyping, DNA samples pre-processed according to Illumina's guidelines are fixed to the GSA microchip and read with an Illumina iScan microarray scanner. The raw data produced by the scanner is then processed using a protocol developed for genotyping data processing, which produces quality controlled genetic data from the raw data for Negen's use.
Genetic data and imputation
Some 660,000 sites, in which variations between people are known to exist, are analysed in the DNA sample using the GSA array. Some of the analysed genome sites are known to contain an allele, or genetic variant, which can cause a predisposition to a disease or even cause a disease on its own. Genome sites causing a predisposition to a disease are also found in regions other than those found on the GSA array. We add the genetic data found in these regions to our data with bioinformatics methods, by means of imputation. The imputation of data is done in co-operation with the National Institute for Health and Welfare Biobank. Data from the genomic analysis conducted previously on thousands of Finns is used in imputation. Based on the genome sites (i.e. genetic variants) analysed on the GSA array, the genetic variant found in many of the other genome sites of the person being examined can be reliably determined. In its results report, Negen explains whether the genetic variant was genotyped directly with a GSA array or imputation was used based on other genetic variants.
Negen's gene tests are based on genetic analyses, whose methods depend on researched diseases. One genotyped genetic variant of certain diseases, such as diseases of the Finnish Disease Heritage, indicates the predisposition of the person being examined or their offspring to a disease. The results of the gene test then simply provide information on whether a person has one, two or none of the risk forms of the genetic variant in their genome. Many different genes, lifestyles, and the environment affect one's predisposition to a wide range of diseases. With respect to these multifactorial diseases, such as coronary heart disease, Negen's genetic analysis tests a large number of the genetic variants linked to the diseases in question in previous scientific studies. The tested genetic variants form a Polygenic Risk Score (PRS), which indicates the number of known genetic variants posing a risk of, for example, coronary heart disease in the genome of the person being examined. In addition to the PRS, a lifestyle survey is conducted to determine general lifestyle and environmental factors that affect the risk of contracting a disease. These include information on tobacco use, blood pressure and family history, i.e. parents suffering from a heart attack or diabetes. Information on the genetic risk of contracting a disease and lifestyle impact are combined to form a percentage that describes a person's risk of contracting a disease. Negen also tests PRSs affecting measurable traits, such as body mass index and cholesterol levels. Where these are concerned, the test produces data on the impact of a person's genome on, for example, body mass index.
The basis for Negen's risk assessments is set by analysing the impact of PRSs (i.e. genetic risk and lifestyle) on the morbidity of FINRISK participants. PRSs were calculated for 22,000 National Institute for Health and Welfare (THL) FINRISK study participants, whose lifestyle factors affecting the risk of disease and their disease history dating as far back as 20 years are known.