| 1. |
|
|
| 2. |
- Kurki, MI, et al.
(författare)
-
FinnGen provides genetic insights from a well-phenotyped isolated population
- 2023
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 613:7944, s. 508-
-
Tidskriftsartikel (refereegranskat)abstract
- Population isolates such as those in Finland benefit genetic research because deleterious alleles are often concentrated on a small number of low-frequency variants (0.1% ≤ minor allele frequency < 5%). These variants survived the founding bottleneck rather than being distributed over a large number of ultrarare variants. Although this effect is well established in Mendelian genetics, its value in common disease genetics is less explored1,2. FinnGen aims to study the genome and national health register data of 500,000 Finnish individuals. Given the relatively high median age of participants (63 years) and the substantial fraction of hospital-based recruitment, FinnGen is enriched for disease end points. Here we analyse data from 224,737 participants from FinnGen and study 15 diseases that have previously been investigated in large genome-wide association studies (GWASs). We also include meta-analyses of biobank data from Estonia and the United Kingdom. We identified 30 new associations, primarily low-frequency variants, enriched in the Finnish population. A GWAS of 1,932 diseases also identified 2,733 genome-wide significant associations (893 phenome-wide significant (PWS), P < 2.6 × 10–11) at 2,496 (771 PWS) independent loci with 807 (247 PWS) end points. Among these, fine-mapping implicated 148 (73 PWS) coding variants associated with 83 (42 PWS) end points. Moreover, 91 (47 PWS) had an allele frequency of <5% in non-Finnish European individuals, of which 62 (32 PWS) were enriched by more than twofold in Finland. These findings demonstrate the power of bottlenecked populations to find entry points into the biology of common diseases through low-frequency, high impact variants.
|
|
| 3. |
|
|
| 4. |
- Partanen, VM, et al.
(författare)
-
Comparison of cytology and human papillomavirus-based primary testing in cervical screening programs in the Nordic countries
- 2021
-
Ingår i: Journal of medical screening. - : SAGE Publications. - 1475-5793 .- 0969-1413. ; 28:4, s. 464-471
-
Tidskriftsartikel (refereegranskat)abstract
- To compare primary test positivity in cytology and human papillomavirus-based screening between different Nordic cervical cancer screening programs using harmonized register data. Methods This study utilized individual-level data available in national databases in Finland, Iceland, Norway, and Sweden. Cervical test data from each country were converted to standard format and aggregated by calculating the number of test episodes for every test result for each calendar year and one-year age group and test method. Test positivity was estimated as the proportion of positive test results of all primary test episodes with a valid test result for “any positive” and “clearly positive” results. Results The age-adjusted rate ratio for any positive test results in primary human papillomavirus-based screening compared to cytology was 1.66 (95% CI 1.64–1.68). The age-adjusted rate ratio for clearly positive test results was 1.02 (95% CI 1.00–1.05). A decreasing rate ratio by age was seen in both any positive and clearly positive test results. Test positivity increased over time in Iceland, Norway, and Sweden but slightly decreased in Finland. Conclusions The probability of any positive test result was higher in human papillomavirus testing than in primary cytology, even though the cross-sectional detection of a clearly positive test result was the same. Human papillomavirus testing can still lead to an improved longitudinal sensitivity through a larger number of follow-up tests and the opportunity to identify women with a persistent human papillomavirus infection. Further research on histologically verified precancerous lesions is needed in primary as well as repeat testing.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Tabassum, R, et al.
(författare)
-
Genetic architecture of human plasma lipidome and its link to cardiovascular disease
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 4329-
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding genetic architecture of plasma lipidome could provide better insights into lipid metabolism and its link to cardiovascular diseases (CVDs). Here, we perform genome-wide association analyses of 141 lipid species (n = 2,181 individuals), followed by phenome-wide scans with 25 CVD related phenotypes (n = 511,700 individuals). We identify 35 lipid-species-associated loci (P <5 ×10−8), 10 of which associate with CVD risk including five new loci-COL5A1, GLTPD2, SPTLC3, MBOAT7 and GALNT16 (false discovery rate<0.05). We identify loci for lipid species that are shown to predict CVD e.g., SPTLC3 for CER(d18:1/24:1). We show that lipoprotein lipase (LPL) may more efficiently hydrolyze medium length triacylglycerides (TAGs) than others. Polyunsaturated lipids have highest heritability and genetic correlations, suggesting considerable genetic regulation at fatty acids levels. We find low genetic correlations between traditional lipids and lipid species. Our results show that lipidomic profiles capture information beyond traditional lipids and identify genetic variants modifying lipid levels and risk of CVD.
|
|
| 8. |
|
|
| 9. |
|
|
