University of Iceland

About: University of Iceland is a education organization based out in Reykjavik, Suðurnes, Iceland. It is known for research contribution in the topics: Population & Genome-wide association study. The organization has 5423 authors who have published 16199 publications receiving 694762 citations. The organization is also known as: Háskóli Íslands.

Improved initial guess for minimum energy path calculations

Abstract: A method is presented for generating a good initial guess of a transition path between given initial and final states of a system without evaluation of the energy. An objective function surface is constructed using an interpolation of pairwise distances at each discretization point along the path and the nudged elastic band method then used to find an optimal path on this image dependent pair potential (IDPP) surface. This provides an initial path for the more computationally intensive calculations of a minimum energy path on an energy surface obtained, for example, by ab initio or density functional theory. The optimal path on the IDPP surface is significantly closer to a minimum energy path than a linear interpolation of the Cartesian coordinates and, therefore, reduces the number of iterations needed to reach convergence and averts divergence in the electronic structure calculations when atoms are brought too close to each other in the initial path. The method is illustrated with three examples: (1) rotation of a methyl group in an ethane molecule, (2) an exchange of atoms in an island on a crystal surface, and (3) an exchange of two Si-atoms in amorphous silicon. In all three cases, the computational effort in finding the minimum energy path with DFT was reduced by a factor ranging from 50% to an order of magnitude by using an IDPP path as the initial path. The time required for parallel computations was reduced even more because of load imbalance when linear interpolation of Cartesian coordinates was used.

Geographic Differences in Genetic Susceptibility to IgA Nephropathy: GWAS Replication Study and Geospatial Risk Analysis

Abstract: IgA nephropathy (IgAN), major cause of kidney failure worldwide, is common in Asians, moderately prevalent in Europeans, and rare in Africans. It is not known if these differences represent variation in genes, environment, or ascertainment. In a recent GWAS, we localized five IgAN susceptibility loci on Chr.6p21 (HLA-DQB1/DRB1, PSMB9/TAP1, and DPA1/DPB2 loci), Chr.1q32 (CFHR3/R1 locus), and Chr.22q12 (HORMAD2 locus). These IgAN loci are associated with risk of other immunemediated disorders such as type I diabetes, multiple sclerosis, or inflammatory bowel disease. We tested association of these loci in eight new independent cohorts of Asian, European, and African-American ancestry (N = 4,789), followed by metaanalysis with risk-score modeling in 12 cohorts (N = 10,755) and geospatial analysis in 85 world populations. Four susceptibility loci robustly replicated and all five loci were genome-wide significant in the combined cohort (P = 5610 232 – 3610 210 ), with heterogeneity detected only at the PSMB9/TAP1 locus (I 2 = 0.60). Conditional analyses identified two new independent risk alleles within the HLA-DQB1/DRB1 locus, defining multiple risk and protective haplotypes within this interval. We also detected a significant genetic interaction, whereby the odds ratio for the HORMAD2 protective allele was reversed in homozygotes for a CFHR3/R1 deletion (P = 2.5610 24 ). A seven–SNP genetic risk score, which explained 4.7% of overall IgAN risk, increased sharply with Eastward and Northward distance from Africa (r = 0.30, P = 3610 2128 ). This model paralleled the known East–West gradient in disease risk. Moreover, the prediction of a South–North axis was confirmed by registry data showing that the prevalence of IgAN–attributable kidney failure is increased in Northern Europe, similar to multiple sclerosis and type I diabetes. Variation at IgAN susceptibility loci correlates with differences in disease prevalence among world populations. These findings inform genetic, biological, and epidemiological investigations of IgAN and permit cross-comparison with other complex traits that share genetic risk loci and geographic patterns with IgAN.

Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease

Abstract: Stacy Steinberg, Hreinn Stefansson, Thorlakur Jonsson and colleagues found that rare variants predicted to alter the function of ABCA7 are associated with risk of Alzheimer's disease. The association was found in Iceland and replicated in northern Europe and the United States. We conducted a search for rare, functional variants altering susceptibility to Alzheimer's disease that exploited knowledge of common variants associated with the same disease. We found that loss-of-function variants in ABCA7 confer risk of Alzheimer's disease in Icelanders (odds ratio (OR) = 2.12, P = 2.2 × 10−13) and discovered that the association replicated in study groups from Europe and the United States (combined OR = 2.03, P = 6.8 × 10−15).

Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome

Abstract: Polycystic ovary syndrome (PCOS) is the most common reproductive disorder in women, yet there is little consensus regarding its aetiology. Here we perform a genome-wide association study of PCOS in up to 5,184 self-reported cases of White European ancestry and 82,759 controls, with follow-up in a further â 1/42,000 clinically validated cases and â 1/4100,000 controls. We identify six signals for PCOS at genome-wide statistical significance (P<5 × 10 â '8), in/near genes ERBB4/HER4, YAP1, THADA, FSHB, RAD50 and KRR1. Variants in/near three of the four epidermal growth factor receptor genes (ERBB2/HER2, ERBB3/HER3 and ERBB4/HER4) are associated with PCOS at or near genome-wide significance. Mendelian randomization analyses indicate causal roles in PCOS aetiology for higher BMI (P=2.5 × 10 â '9), higher insulin resistance (P=6 × 10 â '4) and lower serum sex hormone binding globulin concentrations (P=5 × 10 â '4). Furthermore, genetic susceptibility to later menopause is associated with higher PCOS risk (P=1.6 × 10 â '8) and PCOS-susceptibility alleles are associated with higher serum anti-Mullerian hormone concentrations in girls (P=8.9 × 10 â '5). This large-scale study implicates an aetiological role of the epidermal growth factor receptors, infers causal mechanisms relevant to clinical management and prevention, and suggests balancing selection mechanisms involved in PCOS risk.