Search

Iron is essential for many biological functions and iron deficiency and overload have major health implications. We performed a meta-analysis of three genome-wide association studies from Iceland, the UK and Denmark of blood levels of ferritin (N = 246,139), total iron binding capacity (N = 135,430), iron (N = 163,511) and transferrin saturation (N = 131,471). We found 62 independent sequence variants associating with iron homeostasis parameters at 56 loci, including 46 novel loci. Variants at DUOX2, F5, SLC11A2 and TMPRSS6 associate with iron deficiency anemia, while variants at TF, HFE, TFR2 and TMPRSS6 associate with iron overload. A HBS1L-MYB intergenic region variant associates both with increased risk of iron overload and reduced risk of iron deficiency anemia. The DUOX2 missense variant is present in 14% of the population, associates with all iron homeostasis biomarkers, and increases the risk of iron deficiency anemia by 29%. The associations implicate proteins contributing to the main physiological processes involved in iron homeostasis: iron sensing and storage, inflammation, absorption of iron from the gut, iron recycling, erythropoiesis and bleeding/menstruation., Bell et al. report 46 new loci associated with biomarkers of iron homeostasis, including ferritin levels, iron binding capacity, and iron saturation, in the Icelandic, Danish and UK populations. The associated loci point to new iron-regulating proteins and important genetic differences between men and women.

Publisher's version (útgefin grein)., Bone area is one measure of bone size that is easily derived from dual-energy X-ray absorptiometry (DXA) scans. In a GWA study of DXA bone area of the hip and lumbar spine (N ≥ 28,954), we find thirteen independent association signals at twelve loci that replicate in samples of European and East Asian descent (N = 13,608 – 21,277). Eight DXA area loci associate with osteoarthritis, including rs143384 in GDF5 and a missense variant in COL11A1 (rs3753841). The strongest DXA area association is with rs11614913[T] in the microRNA MIR196A2 gene that associates with lumbar spine area (P = 2.3 × 10−42, β = −0.090) and confers risk of hip fracture (P = 1.0 × 10−8, OR = 1.11). We demonstrate that the risk allele is less efficient in repressing miR-196a-5p target genes. We also show that the DXA area measure contributes to the risk of hip fracture independent of bone density., We thank all the study subjects for their valuable participation, the staff from all studies and the participating physicians. A part of this research has been conducted using the UK Biobank Resource under Application Number 23359. arcOGEN (http://www.arcogen.org.uk/) was funded by a special purpose grant from Arthritis Research UK (grant 18030).

The plasma proteome can help bridge the gap between the genome and diseases. Here we describe genome-wide association studies (GWASs) of plasma protein levels measured with 4,907 aptamers in 35,559 Icelanders. We found 18,084 associations between sequence variants and levels of proteins in plasma (protein quantitative trait loci; pQTL), of which 19% were with rare variants (minor allele frequency (MAF)

Osteoarthritis has a highly negative impact on quality of life because of the associated pain and loss of joint function. Here we describe the largest meta-analysis so far of osteoarthritis of the hip and the knee in samples from Iceland and the UK Biobank (including 17,151 hip osteoarthritis patients, 23,877 knee osteoarthritis patients, and more than 562,000 controls). We found 23 independent associations at 22 loci in the additive meta-analyses, of which 16 of the loci were novel: 12 for hip and 4 for knee osteoarthritis. Two associations are between rare or low-frequency missense variants and hip osteoarthritis, affecting the genes SMO (rs143083812, frequency 0.11%, odds ratio (OR) = 2.8, P = 7.9 × 10-12, p.Arg173Cys) and IL11 (rs4252548, frequency 2.08%, OR = 1.30, P = 2.1 × 10-11, p.Arg112His). A common missense variant in the COL11A1 gene also associates with hip osteoarthritis (rs3753841, frequency 61%, P = 5.2 × 10-10, OR = 1.08, p.Pro1284Leu). In addition, using a recessive model, we confirm an association between hip osteoarthritis and a variant of CHADL1 (rs117018441, P = 1.8 × 10-25, OR = 5.9). Furthermore, we observe a complex relationship between height and risk of osteoarthritis.

The original HTML version of this Article was updated shortly after publication to add links to the Peer Review file.In addition, affiliations 16 and 17 incorrectly read ‘School of Medicine Sydney, University of Notre Dame Australia, Sydney, WA, 6160, Australia’ and ‘St Vincent’s Clinical School, University of New South Wales Medicine, University of New South Wales, Sydney, NSW, 2052, Australia.’ This has now been corrected in both the PDF and HTML versions of the Article.

Classical realism demands that system properties exist independently of whether they are measured, while noncontextuality demands that the results of measurements do not depend on what other measurements are performed in conjunction with them. The Bell–Kochen–Specker theorem states that noncontextual realism cannot reproduce the measurement statistics of a single three-level quantum system (qutrit). Noncontextual realistic models may thus be tested using a single qutrit without relying on the notion of quantum entanglement in contrast to Bell inequality tests. It is challenging to refute such models experimentally, since imperfections may introduce loopholes that enable a realist interpretation. Here we use a superconducting qutrit with deterministic, binary-outcome readouts to violate a noncontextuality inequality while addressing the detection, individual-existence and compatibility loopholes. This evidence of state-dependent contextuality also demonstrates the fitness of superconducting quantum circuits for fault-tolerant quantum computation in surface-code architectures, currently the most promising route to scalable quantum computing., Nature Communications, 7, ISSN:2041-1723

Binary-outcome measurements allow to determine whether a multi-level quantum system is in a certain state while preserving quantum coherence between all orthogonal states. In this paper, we explore different regimes of the dispersive readout of a three-level superconducting quantum system coupled to a microwave cavity in order to implement binary-outcome measurements. By designing identical cavity frequency shifts for the first and second excited states of the system, we realize strong projective binary-outcome measurements onto its ground state with a fidelity of $94.3\%$. Complemented with standard microwave control and low-noise parametric amplification, this scheme enables the quantum non-demolition detection of leakage errors and can be used to create sets of compatible measurements to reveal the contextual nature of superconducting circuits., 9 pages, 4 figures