When Colour Matters: Policing and Hate Crime

Contrary to the image of Sweden as a tolerant, colour-blind and non-racial country, which is based on the narrative of a country for instance associated with solidarity with the so-called Third World; in this article we argue that racial attributes, e.g. visible differences, account for people’s different life possibilities and circumstances in Swedish society. This article explores and discusses whether, and if so why, people who belong to the group that is categorised as “non-white”, with an emphasis on Afroswedes, and depicted as racially different, experience being targets of diverse variations of bias-based policing, harassment and hate crime. Theories relating to colonial stereotypes, racism, doing difference, the geography of hate, race/ethnicity profiling and intersectionality are used to analyse our material. Based on individual and focus group interviews with “non-whites”, this article discusses how visible differences are highlighted in different kinds of social contexts. The interview results show that people with dark skin are often targets of different kinds of private and public policing based on race- and ethnicity profiling that often occurs on or near borders/boundaries. When those who are targets of racial harassment and exclusion resist such treatment, e.g. by crossing borders/boundaries, they are at risk of becoming victims of hate crime

ANGPTL8 protein-truncating variant associated with lower serum triglycerides and risk of coronary disease

Protein-truncating variants (PTVs) affecting dyslipidemia risk may point to therapeutic targets for cardiometabolic disease. Our objective was to identify PTVs that were associated with both lipid levels and the risk of coronary artery disease (CAD) or type 2 diabetes (T2D) and assess their possible associations with risks of other diseases. To achieve this aim, we leveraged the enrichment of PTVs in the Finnish population and tested the association of low-frequency PTVs in 1,209 genes with serum lipid levels in the Finrisk Study (n = 23,435). We then tested which of the lipid-associated PTVs were also associated with the risks of T2D or CAD, as well as 2,683 disease endpoints curated in the FinnGen Study (n = 218,792). Two PTVs were associated with both lipid levels and the risk of CAD or T2D: triglyceride-lowering variants in ANGPTL8 (-24.0[-30.4 to -16.9] mg/dL per rs760351239-T allele, P = 3.4 x 10(-9)) and ANGPTL4 (-14.4[-18.6 to -9.8] mg/dL per rs746226153-G allele, P = 4.3 x 10(-9)). The risk of T2D was lower in carriers of the ANGPTL4 PTV (OR = 0.70[0.60-0.81], P = 2.2 x 10(-6)) than noncarriers. The odds of CAD were 47% lower in carriers of a PTV in ANGPTL8 (OR = 0.53[0.37-0.76], P = 4.5 x 10(-4)) than noncarriers. Finally, the phenome-wide scan of the ANGPTL8 PTV showed that the ANGPTL8 PTV carriers were less likely to use statin therapy (68,782 cases, OR = 0.52[0.40-0.68], P = 1.7 x 10(-6)) compared to noncarriers. Our findings provide genetic evidence of potential long-term efficacy and safety of therapeutic targeting of dyslipidemias. Author summary Studying the health impacts of protein-truncating variants (PTVs) enables detecting the health impact of drugs that inhibit these same genes. Our study aimed to expand our knowledge of genes associated with cardiometabolic disease, along with the side effects of these genes. To detect PTVs associated with cardiometabolic disease, we first performed a genome-wide scan of PTVs associated with serum lipid levels in Finns. We found PTVs in two genes highly enriched in Finns, which were associated with both serum lipid levels and a lower risk of type 2 diabetes or coronary artery disease: ANGPTL4 and ANGPTL8. To evaluate the other health effects of these PTVs, we performed an association scan between the PTVs and 2,683 disease endpoints curated in the FinnGen Study (n = 218,792). We demonstrate that using human populations with PTV-enrichment, such as Finns, offers considerable boosts in statistical power to detect potential long-term efficacy and safety of pharmacologically targeting genes.Peer reviewe

Associated production of H^{\pm} and W^{\mp} in high-energy e+e- collisions in the Minimal Supersymmetric Standard Model

We study the associated production of the charged Higgs boson and W^{\pm} gauge boson in high energy e+e- collisions in the Minimal Supersymmetric Standard Model (MSSM). This associated production, which first arises at the one loop level, offers the possibility of producing the charged Higgs boson at the e+e- collider with mass more than half the center-of-mass energy, when the charged Higgs pair production is kinematically forbidden. We present analytic and numerical results for the cross section for e+e- --> W+ H- in the full MSSM, taking into account the previously uncalculated contributions from supersymmetric (SUSY) particles. We find that the contributions of the SUSY particles enhance the cross section over most of SUSY parameter space, especially when the SUSY particles are light, ~200 GeV. With favorable SUSY parameters, at small tan beta, this process can yield more than ten W^{\pm}H^{\mp} events for m_{H^{\pm}} <~ 350 GeV in 500 fb-1 at a 500 GeV e+e- collider, or m_{H^{\pm}} <~ 600 GeV in 1000 fb-1 at a 1000 GeV collider. 80% left-handed polarization of the e- beam improves these reaches to m_{H^{\pm}} <~ 375 GeV and m_{H^{\pm}} <~ 670 GeV, respectively.Comment: v2: 21 pages, 9 figures, comments on Higgs search bounds and new references added, and minor changes; v3: 23 pages, 11 figures, review of literature moved from introduction to new Sec.5 and 2 plots added, references added, typos corrected; v4: bug fixed in nu nubar H0 cross section (Fig.11), version to appear in PR

Association of the MYOC p.(Gln368Ter) Variant With Glaucoma in a Finnish Population

IMPORTANCE The c.1102C>T, p.(Gln368Ter) variant in themyocilin (MYOC) gene is a known risk allele for glaucoma. It is the most common MYOC risk variant for glaucoma among individuals of European ancestry, and its prevalence is highest in Finland. Furthermore, exfoliation syndrome has high prevalence in Scandinavia, making the Finnish population ideal to study the association of the variant with different types of glaucoma. OBJECTIVES To examine the association and penetrance of MYOC p.(Gln368Ter) (rs74315329) variant with different types of glaucoma in a Finnish population. DESIGN, SETTING, AND PARTICIPANTS This genetic association study included individuals of Finnish ancestry in the FinnGen project. The participants were collected from Finnish biobanks, and the disease end points were defined using nationwide registries. The MYOC c.1102C>T variant was either directly genotyped or imputed with microarrays. Recruitment of samples to FinnGen was initiated in 2017, and data analysis was performed between December 2019 and May 2020. MAIN OUTCOMES AND MEASURES The main outcomes were odds ratios (ORs) and penetrance with different types of glaucoma and in different age groups. RESULTS A total of 218 792 individuals were included in this study (mean [SD] age 52.4 [17.5] years; 123 579 women [56.5%]), including 8591 (3.9%) with glaucoma, 3412 (1.6%) with primary open-angle glaucoma, 1515 (0.7%) with exfoliation glaucoma, 892 (0.4%) with normal-tension glaucoma, and 4766 (2.2%) with suspected glaucoma. The minor allele frequency of MYOC p.(Gln368Ter) was 0.28%. Individuals with the heterozygous variant had higher odds of primary open-angle glaucoma (OR, 3.36; 95% CI, 2.55-4.37), overall glaucoma (OR, 2.58; 95% CI, 2.12-3.13), suspected glaucoma (OR, 2.53; 95% CI, 1.93-3.26), exfoliation glaucoma (OR, 2.61; 95% CI, 1.60-4.02), and undergoing glaucoma-related operations (OR, 5.45; 95% CI, 2.95-9.28). The penetrance of heterozygous MYOC p.(Gln368Ter) was 5.2% in individuals with primary open-angle glaucoma, 9.6% in individuals with glaucoma, 5.4% in individuals with suspected glaucoma, and 1.9% in individuals with exfoliation glaucoma. There was no significant association with normal-tension glaucoma (OR, 1.69; 95% CI, 0.72-3.35). CONCLUSIONS AND RELEVANCE This genetic association study found that the MYOC p.(Gln368Ter) variant was associated with exfoliation glaucoma. The association with normal-tension glaucoma could not be replicated. These findings suggest that MYOC p.(Gln368Ter) was associated with open-angle glaucoma and exfoliation glaucoma in a Finnish population.Peer reviewe

Prospects for heavy supersymmetric charged Higgs boson searches at hadron colliders

We investigate the production of a heavy charged Higgs boson at hadron colliders within the context of the MSSM. A detailed study is performed for all important production modes and basic background processes for the t\bar{t}b\bar{b} signature. In our analysis we include effects of initial and final state showering, hadronization, and principal detector effects. For the signal production rate we include the leading SUSY quantum effects at high \tan\beta>~ mt/mb. Based on the obtained efficiencies for the signal and background we estimate the discovery and exclusion mass limits of the charged Higgs boson at high values of \tan\beta. At the upgraded Tevatron the discovery of a heavy charged Higgs boson (MH^+ >~ 200 GeV) is impossible for the tree-level cross-section values. However, if QCD and SUSY effects happen to reinforce mutually, there are indeed regions of the MSSM parameter space which could provide 3\sigma evidence and, at best, 5\sigma charged Higgs boson discovery at the Tevatron for masses M_H^+<~ 300 GeV and M_H^+<~ 250 GeV, respectively, even assuming squark and gluino masses in the (500-1000) GeV range. On the other hand, at the LHC one can discover a H^+ as heavy as 1 TeV at the canonical confidence level of 5\sigma; or else exclude its existence at 95% C.L. up to masses ~ 1.5 TeV. Again the presence of SUSY quantum effects can be very important here as they may shift the LHC limits by a few hundred GeV.Comment: Latex2e, 44 pages, 15 figures, 6 tables, uses JHEP3.sty, axodraw.sty. Comments added. Discussion on QCD factors clarified. Added discussion on uncertainties. Change of presentation of Tables 4 and 5 and Fig.6. Results and conclusions unchanged. Version accepted in JHE

Genetic risk factors have a substantial impact on healthy life years

The impact of genetic variation on overall disease burden has not been comprehensively evaluated. We introduce an approach to estimate the effect of genetic risk factors on disability-adjusted life years (DALYs; 'lost healthy life years'). We use genetic information from 735,748 individuals and consider 80 diseases. Rare variants had the highest effect on DALYs at the individual level. Among common variants, rs3798220 (LPA) had the strongest individual-level effect, with 1.18 DALYs from carrying 1 versus 0 copies. Being in the top 10% versus the bottom 90% of a polygenic score for multisite chronic pain had an effect of 3.63 DALYs. Some common variants had a population-level effect comparable to modifiable risk factors such as high sodium intake and low physical activity. Attributable DALYs vary between males and females for some genetic exposures. Genetic risk factors can explain a sizable number of healthy life years lost both at the individual and population level.Peer reviewe

Rare protein-altering variants in ANGPTL7 lower intraocular pressure and protect against glaucoma

Protein-altering variants that are protective against human disease provide in vivo validation of therapeutic targets. Here we use genotyping data from UK Biobank (n = 337,151 unrelated White British individuals) and FinnGen (n = 176,899) to conduct a search for protein-altering variants conferring lower intraocular pressure (IOP) and protection against glaucoma. Through rare protein-altering variant association analysis, we find a missense variant in ANGPTL7 in UK Biobank (rs28991009, p.Gln175His, MAF = 0.8%, genotyped in 82,253 individuals with measured IOP and an independent set of 4,238 glaucoma patients and 250,660 controls) that significantly lowers IOP (beta = -0.53 and -0.67 mmHg for heterozygotes, -3.40 and -2.37 mmHg for homozygotes, P = 5.96 x 10(-9) and 1.07 x 10(-13) for corneal compensated and Goldman-correlated IOP, respectively) and is associated with 34% reduced risk of glaucoma (P = 0.0062). In FinnGen, we identify an ANGPTL7 missense variant at a greater than 50-fold increased frequency in Finland compared with other populations (rs147660927, p.Arg220Cys, MAF Finland = 4.3%), which was genotyped in 6,537 glaucoma patients and 170,362 controls and is associated with a 29% lower glaucoma risk (P = 1.9 x 10(-12) for all glaucoma types and also protection against its subtypes including exfoliation, primary open-angle, and primary angle-closure). We further find three rarer variants in UK Biobank, including a protein-truncating variant, which confer a strong composite lowering of IOP (P = 0.0012 and 0.24 for Goldman-correlated and corneal compensated IOP, respectively), suggesting the protective mechanism likely resides in the loss of interaction or function. Our results support inhibition or down-regulation of ANGPTL7 as a therapeutic strategy for glaucoma. Author summary Glaucoma is a common eye disease that damages the optic nerve. Using intraocular pressure, which is a known modifiable risk factor and predictive measure for glaucoma, genome-wide association studies have identified dozens of genetic variants likely affecting disease risk. However, the identification of potential therapeutic targets from those discoveries has been challenging because the functional consequences and the causal variants of the suggested common variant associations are typically unclear. Here, we present a strategy to scan for rare protein-altering variants, which provides direct insights into the functional consequence and the therapeutic effects, using more than 514,000 individuals with European ancestries in two population cohorts in the UK and Finland. We discover an allelic series of multiple rare ANGPTL7 missense and nonsense variants in UK Biobank that lower intraocular pressure and reduces the risk of glaucoma. We further identify an ANGPTL7 missense variant in FinnGen cohort with more than 50-fold enrichment in the Finnish population that provides protection against glaucoma and its subtypes. Our results highlight the benefits of multi-cohort analysis for the discovery of rare protein-altering variants in common diseases and indicate ANGPTL7 as a therapeutic target for glaucoma.Peer reviewe

Genomic prediction of alcohol-related morbidity and mortality

While polygenic risk scores (PRS) have been shown to predict many diseases and risk factors, the potential of genomic prediction in harm caused by alcohol use has not yet been extensively studied. Here, we built a novel polygenic risk score of 1.1 million variants for alcohol consumption and studied its predictive capacity in 96,499 participants from the FinnGen study and 39,695 participants from prospective cohorts with detailed baseline data and up to 25 years of follow-up time. A 1 SD increase in the PRS was associated with 11.2 g (=0.93 drinks) higher weekly alcohol consumption (CI = 9.85-12.58 g, p = 2.3 x 10(-58)). The PRS was associated with alcohol-related morbidity (4785 incident events) and the risk estimate between the highest and lowest quintiles of the PRS was 1.83 (95% CI = 1.66-2.01, p = 1.6 x 10(-36)). When adjusted for self-reported alcohol consumption, education, marital status, and gamma-glutamyl transferase blood levels in 28,639 participants with comprehensive baseline data from prospective cohorts, the risk estimate between the highest and lowest quintiles of the PRS was 1.58 (CI = 1.26-1.99, p = 8.2 x 10(-5)). The PRS was also associated with all-cause mortality with a risk estimate of 1.33 between the highest and lowest quintiles (CI = 1.20-1.47, p = 4.5 x 10(-8)) in the adjusted model. In conclusion, the PRS for alcohol consumption independently associates for both alcohol-related morbidity and all-cause mortality. Together, these findings underline the importance of heritable factors in alcohol-related health burden while highlighting how measured genetic risk for an important behavioral risk factor can be used to predict related health outcomes.Peer reviewe

TESLA Technical Design Report Part III: Physics at an e+e- Linear Collider

The TESLA Technical Design Report Part III: Physics at an e+e- Linear ColliderComment: 192 pages, 131 figures. Some figures have reduced quality. Full quality figures can be obtained from http://tesla.desy.de/tdr. Editors - R.-D. Heuer, D.J. Miller, F. Richard, P.M. Zerwa

Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers

Polygenic risk scores (PRSs) have shown promise in predicting susceptibility to common diseases1,2,3. We estimated their added value in clinical risk prediction of five common diseases, using large-scale biobank data (FinnGen; n = 135,300) and the FINRISK study with clinical risk factors to test genome-wide PRSs for coronary heart disease, type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer. We evaluated the lifetime risk at different PRS levels, and the impact on disease onset and on prediction together with clinical risk scores. Compared to having an average PRS, having a high PRS contributed 21% to 38% higher lifetime risk, and 4 to 9 years earlier disease onset. PRSs improved model discrimination over age and sex in type 2 diabetes, atrial fibrillation, breast cancer and prostate cancer, and over clinical risk in type 2 diabetes, breast cancer and prostate cancer. In all diseases, PRSs improved reclassification over clinical thresholds, with the largest net reclassification improvements for early-onset coronary heart disease, atrial fibrillation and prostate cancer. This study provides evidence for the additional value of PRSs in clinical disease prediction. The practical applications of polygenic risk information for stratified screening or for guiding lifestyle and medical interventions in the clinical setting remain to be defined in further studies.Peer reviewe