| 1. |
- Chen, X., et al.
(author)
-
A genome-wide association study of IgM antibody against phosphorylcholine: shared genetics and phenotypic relationship to chronic lymphocytic leukemia
- 2018
-
In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 27:10, s. 1809-1818
-
Journal article (peer-reviewed)abstract
- Phosphorylcholine (PC) is an epitope on oxidized low-density lipoprotein (oxLDL), apoptotic cells and several pathogens like Streptococcus pneumoniae. Immunoglobulin M against PC (IgM anti-PC) has the ability to inhibit uptake of oxLDL by macrophages and increase clearance of apoptotic cells. From our genome-wide association studies (GWASs) in four European-ancestry cohorts, six single nucleotide polymorphisms (SNPs) in 11q24.1 were discovered (in 3002 individuals) and replicated (in 646 individuals) to be associated with serum level of IgM anti-PC (the leading SNP rs35923643-G, combined beta = 0.19, 95% confidence interval 0.13-0.24, P = 4.3 x 10-11). The haplotype tagged by rs35923643-G (or its proxy SNP rs735665-A) is also known as the top risk allele for chronic lymphocytic leukemia (CLL), and a main increasing allele for general IgM. By using summary GWAS results of IgM anti-PC and CLL in the polygenic risk score (PRS) analysis, PRS on the basis of IgM anti-PC risk alleles positively associated with CLL risk (explained 0.6% of CLL variance, P = 1.2 x 10-15). Functional prediction suggested that rs35923643-G might impede the binding of Runt-related transcription factor 3, a tumor suppressor playing a central role in the immune regulation of cancers. Contrary to the expectations from the shared genetics between IgM anti-PC and CLL, an inverse relationship at the phenotypic level was found in a nested case-control study (30 CLL cases with 90 age- and sex-matched controls), potentially reflecting reverse causation. The suggested function of the top variant as well as the phenotypic association between IgM anti-PC and CLL risk needs replication and motivates further studies.
|
|
| 2. |
- Franceschini, N., et al.
(author)
-
GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes
- 2018
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Journal article (peer-reviewed)abstract
- Carotid artery intima media thickness (cIMT) and carotid plaque are measures of subclinical atherosclerosis associated with ischemic stroke and coronary heart disease (CHD). Here, we undertake meta-analyses of genome-wide association studies (GWAS) in 71,128 individuals for cIMT, and 48,434 individuals for carotid plaque traits. We identify eight novel susceptibility loci for cIMT, one independent association at the previously-identified PINX1 locus, and one novel locus for carotid plaque. Colocalization analysis with nearby vascular expression quantitative loci (cis-eQTLs) derived from arterial wall and metabolic tissues obtained from patients with CHD identifies candidate genes at two potentially additional loci, ADAMTS9 and LOXL4. LD score regression reveals significant genetic correlations between cIMT and plaque traits, and both cIMT and plaque with CHD, any stroke subtype and ischemic stroke. Our study provides insights into genes and tissue-specific regulatory mechanisms linking atherosclerosis both to its functional genomic origins and its clinical consequences in humans. © 2018, The Author(s).
|
|
| 3. |
|
|
| 4. |
- Wang, Yunzhang, et al.
(author)
-
Epigenetic influences on aging : a longitudinal genome-wide methylation study in old Swedish twins
- 2018
-
In: Epigenetics. - : Informa UK Limited. - 1559-2294 .- 1559-2308. ; 13:9, s. 975-987
-
Journal article (peer-reviewed)abstract
- Age-related changes in DNA methylation were observed in cross-sectional studies, but longitudinal evidence is still limited. Here, we aimed to characterize longitudinal age-related methylation patterns using 1011 blood samples collected from 385 Swedish twins (age at entry: mean 69 and standard deviation 9.7, 73 monozygotic and 96 dizygotic pairs) up to five times (mean 2.6) over 20 years (mean 8.7). We identified 1316 age-associated methylation sites (P<1.3x10(-7)) using a longitudinal epigenome-wide association study design. We measured how estimated cellular compositions changed with age and how much they confounded the age effect. We validated the results in two independent longitudinal cohorts, where 118 CpGs were replicated in Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS, 390 samples) (P<3.9x10(-5)), 594 in Lothian Birth Cohort (LBC, 3018 samples) (P<5.1x10(-5)) and 63 in both. Functional annotation of age-associated CpGs showed enrichment in CCCTC-binding factor (CTCF) and other transcription factor binding sites. We further investigated genetic influences on methylation and found no interaction between age and genetic effects in the 1316 age-associated CpGs. Moreover, in the same CpGs, methylation differences within twin pairs increased with 6.4% over 10 years, where monozygotic twins had smaller intra-pair differences than dizygotic twins. In conclusion, we show that age-related methylation changes persist in a longitudinal perspective, and are fairly stable across cohorts. The changes are under genetic influence, although this effect is independent of age. Moreover, methylation variability increase over time, especially in age-associated CpGs, indicating the increase of environmental contributions on DNA methylation with age.
|
|
| 5. |
- Almgren, Erik, et al.
(author)
-
Brandförlopp
- 2012
-
In: Brandskyddshandboken - En handbok för projektering av brandskydd i byggnader. - 1402-3504. ; , s. 211-228
-
Book chapter (peer-reviewed)
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
- Almgren, Malin, et al.
(author)
-
Adenovirus-36 Is Associated with Obesity in Children and Adults in Sweden as Determined by Rapid ELISA
- 2012
-
In: PLOS ONE. - : PUBLIC LIBRARY SCIENCE. - 1932-6203. ; 7:7
-
Journal article (peer-reviewed)abstract
- Background: Experimental and natural human adenovirus-36 (Adv36) infection of multiple animal species results in obesity through increasing adipogenesis and lipid accumulation in adipocytes. Presence of Adv36 antibodies detected by serum neutralization assay has previously been associated with obesity in children and adults living in the USA, South Korea and Italy, whereas no association with adult obesity was detected in Belgium/the Netherlands nor among USA military personnel. Adv36 infection has also been shown to reduce blood lipid levels, increase glucose uptake by adipose tissue and skeletal muscle biopsies, and to associate with improved glycemic control in non-diabetic individuals. Principal Findings: Using a novel ELISA, 1946 clinically well-characterized individuals including 424 children and 1522 nondiabetic adults, and 89 anonymous blood donors, residing in central Sweden representing the population in Stockholm area, were studied for the presence of antibodies against Adv36 in serum. The prevalence of Adv36 positivity in lean individuals increased from similar to 7% in 1992-1998 to 15-20% in 2002-2009, which paralleled the increase in obesity prevalence. We found that Adv36-positive serology was associated with pediatric obesity and with severe obesity in females compared to lean and overweight/mildly obese individuals, with a 1.5 to 2-fold Adv36 positivity increase in cases. Moreover, Adv36 positivity was less common among females and males on antilipid pharmacological treatment or with high blood triglyceride level. Insulin sensitivity, measured as lower HOMA-IR, showed a higher point estimate in Adv36-positive obese females and males, although it was not statistically significant (p = 0.08). Conclusion: Using a novel ELISA we show that Adv36 infection is associated with pediatric obesity, severe obesity in adult females and lower risk of high blood lipid levels in non-diabetic Swedish individuals.
|
|
| 9. |
- Amnå, Erik, 1950, et al.
(author)
-
The end of a distinctive model of democracy? Country-diverse orientations among young adult Scandinavians
- 2007
-
In: Scandinavian Political Studies. - 0080-6757. ; 30:1, s. 61-86
-
Journal article (peer-reviewed)abstract
- International research into democracy has uncovered severe changes in patterns of political engagement and participation. Even political institutions such as political parties and voluntary organisations have undergone major alterations. Scandinavian democracies hitherto have been regarded as exceptionally stable and strong due to their homogenous qualities of mass-based class politics, strong political parties, high degree of associationalism, peaceful labour market relations and developed welfare policies. However, three official democratic audits recently revealed that Scandinavian democracies have also been severely affected by both exogenous and endogenous constraints. In addition, Scandinavian democracies appear to be diverging heterogeneously from the assumed 'pan-Scandinavian' model. This article examines whether the distinctive country characteristics uncovered by the commissions can be traced among young adults. Three dimensions of attitudes of young adults are analysed ? political trust, political engagement and political equality ? using survey data obtained from students in academic programmes at the upper secondary level in Denmark, Norway and Sweden in 2000. Generally, the results not only confirm a country diversity that threatens to jeopardise Scandinavian homogeneity, since the Danes stand out as superior in most measures of political participation, but also, from an international perspective, young Scandinavians cannot be characterised as the most politically interested or participative between elections or even as the most multiculturally tolerant among today's youth.
|
|
| 10. |
|
|
