Fourteen sequence variants that associate with multiple sclerosis discovered by meta-analysis informed by genetic correlations

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked FilesA meta-analysis of publicly available summary statistics on multiple sclerosis combined with three Nordic multiple sclerosis cohorts (21,079 cases, 371,198 controls) revealed seven sequence variants associating with multiple sclerosis, not reported previously. Using polygenic risk scores based on public summary statistics of variants outside the major histocompatibility complex region we quantified genetic overlap between common autoimmune diseases in Icelanders and identified disease clusters characterized by autoantibody presence/absence. As multiple sclerosis-polygenic risk scores captures the risk of primary biliary cirrhosis and vice versa (P = 1.6 x 10(-7), 4.3 x 10(-9)) we used primary biliary cirrhosis as a proxy-phenotype for multiple sclerosis, the idea being that variants conferring risk of primary biliary cirrhosis have a prior probability of conferring risk of multiple sclerosis. We tested 255 variants forming the primary biliary cirrhosis-polygenic risk score and found seven multiple sclerosis-associating variants not correlated with any previously established multiple sclerosis variants. Most of the variants discovered are close to or within immune-related genes. One is a low-frequency missense variant in TYK2, another is a missense variant in MTHFR that reduces the function of the encoded enzyme affecting methionine metabolism, reported to be dysregulated in multiple sclerosis brain.Swedish Research Council Knut and Alice Wallenberg Foundation AFA Foundation Swedish Brain Foundatio

Iodine status of pregnant women in a population changing from high to lower fish and milk consumption.

To access publisher's full text version of this article. Please click on the hyperlink in Additional Links field.Pregnancy is one of the most critical periods for iodine deficiency. The aim of the present study was to assess the iodine status and dietary intake of pregnant women in a population changing from high to lower consumption of milk and fish.Cross-sectional observational study. Urine samples were collected for measuring urinary iodine concentration (UIC) and creatinine, and blood samples for measuring serum thyroid-stimulating hormone (TSH). Frequency of consumption of selected food and beverages was obtained through a semi-quantitative validated FFQ. The difference in the distribution of UIC, ratio of iodine to creatinine (I:Cr) and TSH between groups following recommendations on fish and dairy product intake or not (fish ≥2 times/week as a main meal, diary products ≥2 portions/d) was assessed.Primary Health Care of the Capital Area, Reykjavik, Iceland.Randomly selected pregnant women (19-43 years old, n 162).The median UIC was 180 μg/l, I:Cr 173 μg/g and TSH 1·5 mmol/l. Women who did not consume fish ≥2 times/week and also did not consume dairy products in line with the recommended intake level of ≥2 portions/d had median UIC of 160 μg/l (I:Cr 149 μg/g) compared with 220 μg/l (I:Cr 190 μg/g) in the group following both the recommendations for fish and those for dairy products. Use of dietary supplements in the two groups was similar.Iodine status in the population studied was within the optimal range (150-249 μg/d) defined by the WHO.RANNIS - the Icelandic Centre for Research/ 07042302

Alpaca embryo transfer at Canchones, Dr. Jane Vaughan uses an ultrasound scan to check recipient female Alpaca for gynaecological suitability before transferring an embryo, Taggerty, Victoria, 2007 [picture] /

Title devised by cataloguer based on caption list supplied by photographer.; Acquired in digital format; access copy available online.; Mode of access: Internet via World Wide Web.; Purchased frm the photographer, June Orford, 2007

Fluoride/Calcium in Osteoporosis

To the Editor: We would like to comment on why we believe that a number of the patients of Riggs et al.1 did not respond to their therapy (February 25 issue). Using double tetracycline-labeling techniques, we have found that a substantial number of patients with axial osteopenia have osteomalacia, as defined by the presence of wide osteoid seams (over 10 μm) and reduced tetracycline uptake, rather than osteoporosis.2 Since Riggs et al. did not perform bone biopsies before therapy, a large number of the patients may not have responded to the treatment because they were being treated for the wrong

Incremental Fermi Large Area Telescope Fourth Source Catalog

We present an incremental version (4FGL-DR3, for Data Release 3) of the fourth Fermi Large Area Telescope (LAT) catalog of γ-ray sources. Based on the first 12 years of science data in the energy range from 50 MeV to 1 TeV, it contains 6658 sources. The analysis improves on that used for the 4FGL catalog over eight years of data: more sources are fit with curved spectra, we introduce a more robust spectral parameterization for pulsars, and we extend the spectral points to 1 TeV. The spectral parameters, spectral energy distributions, and associations are updated for all sources. Light curves are rebuilt for all sources with 1 yr intervals (not 2 month intervals). Among the 5064 original 4FGL sources, 16 were deleted, 112 are formally below the detection threshold over 12 yr (but are kept in the list), while 74 are newly associated, 10 have an improved association, and seven associations were withdrawn. Pulsars are split explicitly between young and millisecond pulsars. Pulsars and binaries newly detected in LAT sources, as well as more than 100 newly classified blazars, are reported. We add three extended sources and 1607 new point sources, mostly just above the detection threshold, among which eight are considered identified, and 699 have a plausible counterpart at other wavelengths. We discuss the degree-scale residuals to the global sky model and clusters of soft unassociated point sources close to the Galactic plane, which are possibly related to limitations of the interstellar emission model and missing extended sources

Incremental Fermi Large Area Telescope Fourth Source Catalog

We present an incremental version (4FGL-DR3, for Data Release 3) of the fourth Fermi-LAT catalog of gamma-ray sources. Based on the first twelve years of science data in the energy range from 50 MeV to 1 TeV, it contains 6658 sources. The analysis improves on that used for the 4FGL catalog over eight years of data: more sources are fit with curved spectra, we introduce a more robust spectral parameterization for pulsars, and we extend the spectral points to 1 TeV. The spectral parameters, spectral energy distributions, and associations are updated for all sources. Light curves are rebuilt for all sources with 1 yr intervals (not 2 month intervals). Among the 5064 original 4FGL sources, 16 were deleted, 112 are formally below the detection threshold over 12 yr (but are kept in the list), while 74 are newly associated, 10 have an improved association, and seven associations were withdrawn. Pulsars are split explicitly between young and millisecond pulsars. Pulsars and binaries newly detected in LAT sources, as well as more than 100 newly classified blazars, are reported. We add three extended sources and 1607 new point sources, mostly just above the detection threshold, among which eight are considered identified, and 699 have a plausible counterpart at other wavelengths. We discuss degree-scale residuals to the global sky model and clusters of soft unassociated point sources close to the Galactic plane, which are possibly related to limitations of the interstellar emission model and missing extended sources