| 1. |
|
|
| 2. |
- Ahluwalia, T. S., et al.
(författare)
-
Genome-wide association study of circulating interleukin 6 levels identifies novel loci
- 2021
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 30:5, s. 393-409
-
Tidskriftsartikel (refereegranskat)abstract
- Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67428 (n(discovery)=52654 and n(replication)=14774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (P-combined=1.8x10(-11)), HLA-DRB1/DRB5 rs660895 on Chr6p21 (P-combined=1.5x10(-10)) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (P-combined=1.2x10(-122)). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
|
|
| 3. |
|
|
| 4. |
- Kivipelto, Miia, et al.
(författare)
-
World-Wide FINGERS Network : A global approach to risk reduction and prevention of dementia
- 2020
-
Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 16:7, s. 1078-1094
-
Tidskriftsartikel (refereegranskat)abstract
- Reducing the risk of dementia can halt the worldwide increase of affected people. The multifactorial and heterogeneous nature of late-onset dementia, including Alzheimer's disease (AD), indicates a potential impact of multidomain lifestyle interventions on risk reduction. The positive results of the landmark multidomain Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (FINGER) support such an approach. The World-Wide FINGERS (WW-FINGERS), launched in 2017 and including over 25 countries, is the first global network of multidomain lifestyle intervention trials for dementia risk reduction and prevention. WW-FINGERS aims to adapt, test, and optimize the FINGER model to reduce risk across the spectrum of cognitive decline-from at-risk asymptomatic states to early symptomatic stages-in different geographical, cultural, and economic settings. WW-FINGERS aims to harmonize and adapt multidomain interventions across various countries and settings, to facilitate data sharing and analysis across studies, and to promote international joint initiatives to identify globally implementable and effective preventive strategies.
|
|
| 5. |
- Recknagel, Hans, et al.
(författare)
-
The functional genetic architecture of egg-laying and live-bearing reproduction in common lizards
- 2021
-
Ingår i: Nature Ecology & Evolution. - : Springer Nature. - 2397-334X. ; 5:11, s. 1546-1556
-
Tidskriftsartikel (refereegranskat)abstract
- All amniotes reproduce either by egg-laying (oviparity), which is ancestral to vertebrates or by live-bearing (viviparity), which has evolved many times independently. However, the genetic basis of these parity modes has never been resolved and, consequently, its convergence across evolutionary scales is currently unknown. Here, we leveraged natural hybridizations between oviparous and viviparous common lizards (Zootoca vivipara) to describe the functional genes and genetic architecture of parity mode and its key traits, eggshell and gestation length, and compared our findings across vertebrates. In these lizards, parity trait genes were associated with progesterone-binding functions and enriched for tissue remodelling and immune system pathways. Viviparity involved more genes and complex gene networks than did oviparity. Angiogenesis, vascular endothelial growth and adrenoreceptor pathways were enriched in the viviparous female reproductive tissue, while pathways for transforming growth factor were enriched in the oviparous. Natural selection on these parity mode genes was evident genome-wide. Our comparison to seven independent origins of viviparity in mammals, squamates and fish showed that genes active in pregnancy were related to immunity, tissue remodelling and blood vessel generation. Therefore, our results suggest that pre-established regulatory networks are repeatedly recruited for viviparity and that these are shared at deep evolutionary scales. Using natural hybrids between oviparous and viviparous common lizards, the authors describe the genetic architecture of parity mode and conduct a comparative analysis of genes associated with viviparity in mammals, squamates and fish.
|
|
