Vitamin D status and association with gestational diabetes mellitus in a pregnant cohort in Iceland.

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 DownloadBackground: Vitamin D deficiency has been associated with an increased risk of gestational diabetes mellitus (GDM), one of the most common pregnancy complications. The vitamin D status has never previously been studied in pregnant women in Iceland. Objective: The aim of this research study was to evaluate the vitamin D status of an Icelandic cohort of pregnant women and the association between the vitamin D status and the GDM incidence. Design: Subjects included pregnant women (n = 938) who attended their first ultrasound appointment, during gestational weeks 11-14, between October 2017 and March 2018. The use of supplements containing vitamin D over the previous 3 months, height, pre-pregnancy weight, and social status were assessed using a questionnaire, and blood samples were drawn for analyzing the serum 25‑hydroxyvitamin D (25OHD) concentration. Information regarding the incidence of GDM later in pregnancy was collected from medical records. Results: The mean ± standard deviation of the serum 25OHD (S-25OHD) concentration in this cohort was 63±24 nmol/L. The proportion of women with an S-25OHD concentration of ≥ 50 nmol/L (which is considered adequate) was 70%, whereas 25% had concentrations between 30 and 49.9 nmol/L (insufficient) and 5% had concentrations < 30 nmol/L (deficient). The majority of women (n = 766, 82%) used supplements containing vitamin D on a daily basis. A gradual decrease in the proportion of women diagnosed with GDM was reported with increasing S-25OHD concentrations, going from 17.8% in the group with S-25OHD concentrations < 30 nmol/L to 12.8% in the group with S-25OHD concentrations ≥75 nmol/L; however, the association was not significant (P for trend = 0.11). Conclusion: Approximately one-third of this cohort had S-25OHD concentrations below adequate levels (< 50 nmol/L) during the first trimester of pregnancy, which may suggest that necessary action must be taken to increase their vitamin D levels. No clear association was observed between the vitamin D status and GDM in this study. Keywords: cod liver oil; gestational diabetes mellitus; nutritional status; pregnancy; supplements; vitamin D.University of Iceland Research Fund Science Fund of Landspitali National University Hospita

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Correlation between intake of fish or supplements containing omega-3 fatty acids and early pregnancy plasma concentrations.

Publisher Copyright: © 2022 Laeknafelag Islands. All rights reserved.TILGANGUR Fyrri rannsóknir benda til að hluti barnshafandi kvenna á Íslandi uppfylli ekki ráðlögð viðmið fyrir neyslu langra ómega-3 fitusýra, sem eru taldar mikilvægar fyrir fósturþroska. Markmið rannsóknarinnar var að meta neyslutíðni barnshafandi kvenna á fæðutegundum og bætiefnum sem innihalda langar fjölómettaðar ómega-3 fitusýrur og kanna fylgni við styrk þeirra í blóðvökva. AÐFERÐIR Þátttakendur voru 853 barnshafandi konur sem mættu í fósturgreiningu við 11.-14. viku meðgöngu. Upplýsingar um fæðuval, notkun ómega-3 bætiefna sem innihalda eikósapentaensýru (EPA) og dókósahexaensýru (DHA) og bakgrunn þátttakenda var aflað með fæðutíðnispurningalista. Blóðsýni voru tekin til mælinga á styrk fitusýra í blóðvökva. Fylgni var metin með Spearman-fylgnistuðli. NIÐURSTÖÐUR Miðgildi neyslu á mögrum fiski var 1,3 skipti í viku og á feitum fiski eitt skipti í mánuði. Um 50% tóku ómega-3 bætiefni daglega eða oftar. Hærri heildartíðni fiskneyslu og notkun bætiefna með ómega-3 fitusýrum endurspeglaðist í hærri heildarstyrk þeirra í blóðvökva (r=0,37, p ÁLYKTANIR Neysla matvæla og bætiefna sem innihalda ómega-3 fitusýrur endurspeglaðist í styrk þeirra í blóðvökva, að undanskildu íslensku meðgöngu-fjölvítamíni. Helstu niðurstöður okkar eru að rétt rúmlega þriðjungur barnshafandi kvenna borðaði fisk að minnsta kosti tvisvar sinnum í viku í samræmi við ráðleggingar. Um það bil helmingur kvennanna notaði einhver bætiefni með ómega-3 fitusýrum daglega. INTRODUCTION: Long-chain polyunsaturated omega-3 fatty acids are considered important for fetal development, but previous studies suggest suboptimal intake in part of pregnant women in Iceland. The study aim was to evaluate intake of food and supplements containing omega-3 fatty acids, among pregnant women in Iceland and correlations to fatty acid composition in plasma. MATERIALS AND METHODS: Subjects were 853 pregnant women attending their 11-14 weeks ultrasound appointment. Information on intake of food and supplements containing long-chain omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) as well as background was obtained by a questionnaire. Blood samples were collected for analysis of plasma fatty acids. Correlation was evaluated using the Spearman correlation. RESULTS: Median intake of lean fish was 1.3 times per week, while fatty fish was consumed once monthly. About 50% of the women took omega-3 containing supplements daily. Higher intake of both fish and omega-3 containing supplements was reflected in higher omega-3 plasma levels (r=0.37 p CONCLUSION: Intake of food and supplements containing omega-3 fatty acids was reflected in plasma concentration, except for an Icelandic maternal multivitamin. One third of the women followed the recommendation of eating fish at least twice weekly. About 50% had a daily intake of supplements containing omega-3 fatty acids.INTRODUCTION: Long-chain polyunsaturated omega-3 fatty acids are considered important for fetal development, but previous studies suggest suboptimal intake in part of pregnant women in Iceland. The study aim was to evaluate intake of food and supplements containing omega-3 fatty acids, among pregnant women in Iceland and correlations to fatty acid composition in plasma. MATERIALS AND METHODS: Subjects were 853 pregnant women attending their 11-14 weeks ultrasound appointment. Information on intake of food and supplements containing long-chain omega-3 fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) as well as background was obtained by a questionnaire. Blood samples were collected for analysis of plasma fatty acids. Correlation was evaluated using the Spearman correlation. RESULTS: Median intake of lean fish was 1.3 times per week, while fatty fish was consumed once monthly. About 50% of the women took omega-3 containing supplements daily. Higher intake of both fish and omega-3 containing supplements was reflected in higher omega-3 plasma levels (r=0.37 p<0.001). A positive correlation was seen between intake of cod liver oil/capsules (r=0.23, p=0.001), omega-3 oil/capsules (r=0.20, p=0.001) and plasma concentration of omega-3. However, no correlation was seen between intake of a maternal multivitamin containing omega-3 and corresponding plasma concentration (r=0.03, p=0.98). CONCLUSION: Intake of food and supplements containing omega-3 fatty acids was reflected in plasma concentration, except for an Icelandic maternal multivitamin. One third of the women followed the recommendation of eating fish at least twice weekly. About 50% had a daily intake of supplements containing omega-3 fatty acids.Peer reviewe

Meta-analyses identify 13 loci associated with age at menopause and highlight DNA repair and immune pathways

To newly identify loci for age at natural menopause, we carried out a meta-analysis of 22 genome-wide association studies (GWAS) in 38,968 women of European descent, with replication in up to 14,435 women. In addition to four known loci, we identified 13 loci newly associated with age at natural menopause (at P < 5 x 10(-8)). Candidate genes located at these newly associated loci include genes implicated in DNA repair (EXO1, HELQ, UIMC1, FAM175A, FANCI, TLK1, POLG and PRIM1) and immune function (IL11, NLRP11 and PRRC2A (also known as BAT2)). Gene-set enrichment pathway analyses using the full GWAS data set identified exoDNase, NF-kappaB signaling and mitochondrial dysfunction as biological processes related to timing of menopause

Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies

To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing

Evidence for three genetic loci involved in both anorexia nervosa risk and variation of body mass index

The maintenance of normal body weight is disrupted in patients with anorexia nervosa (AN) for prolonged periods of time. Prior to the onset of AN, premorbid body mass index (BMI) spans the entire range from underweight to obese. After recovery, patients have reduced rates of overweight and obesity. As such, loci involved in body weight regulation may also be relevant for AN and vice versa. Our primary analysis comprised a cross-trait analysis of the 1000 single-nucleotide polymorphisms (SNPs) with the lowest P-values in a genome-wide association meta-analysis (GWAMA) of AN (GCAN) for evidence of association in the largest published GWAMA for BMI (GIANT). Subsequently we performed sex-stratified analyses for these 1000 SNPs. Functional ex vivo studies on four genes ensued. Lastly, a look-up of GWAMA-derived BMI-related loci was performed in the AN GWAMA. We detected significant associations (P-values <5 × 10-5, Bonferroni-corrected P<0.05) for nine SNP alleles at three independent loci. Interestingly, all AN susceptibility alleles were consistently associated with increased BMI. None of the genes (chr. 10: CTBP2, chr. 19: CCNE1, chr. 2: CARF and NBEAL1; the latter is a region with high linkage disequilibrium) nearest to these SNPs has previously been associated with AN or obesity. Sex-stratified analyses revealed that the strongest BMI signal originated predominantly from females (chr. 10 rs1561589; Poverall: 2.47 × 10-06/Pfemales: 3.45 × 10-07/Pmales: 0.043). Functional ex vivo studies in mice revealed reduced hypothalamic expression of Ctbp2 and Nbeal1 after fasting. Hypothalamic expression of Ctbp2 was increased in diet-induced obese (DIO) mice as compared with age-matched lean controls. We observed no evidence for associations for the look-up of BMI-related loci in the AN GWAMA. A cross-trait analysis of AN and BMI loci revealed variants at three chromosomal loci with potential joint impact. The chromosome 10 locus is particularly promising given that the association with obesity was primarily driven by females. In addition, the detected altered hypothalamic expression patterns of Ctbp2 and Nbeal1 as a result of fasting and DIO implicate these genes in weight regulation

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility, and BRCA1-mediated DNA repair [editorial comment]

ABSTRACT: Menopause timing has a major impact on infertility and risk of disease. Younger age at natural (nonsurgical) menopause (ANM) is associated with a higher risk of osteoporosis, cardiovascular disease, and type 2 diabetes and a lower risk of breast cancer. Late menopause is associated with a higher risk of breast cancer. It is well known that the age at which women go through menopause is partly determined by genes, but the underlying mechanisms are poorly understood. Genome-wide association studies have identified 18 common genetic variants associated with ANM. These variants explain less than 5% of the variation in ANM compared with the 21% explained by all common variants on genome-wide association study arrays. This genome-wide association study was the collaborative effort of researchers from 177 institutions worldwide. The study was designed to investigate genetic variants associated with timing of menopause among a population of approximately 70,000 women of European ancestry. A dual strategy was used to identify both common and, for the first time, low-frequency coding variants associated with ANM. The causal relationship between ANM and breast cancer was investigated using a Mendelian randomization approach. Combined analysis identified 1208 single-nucleotide polymorphisms (SNPs) of a total of approximately 2.6 million that reached the genome-wide significance threshold for association with ANM. Forty-four regions with common variants were identified; among these 44 loci were 2 rare low-frequency missense alleles of large effect. A majority of ANM SNPs were enriched in DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal relationship between delayed ANM and breast cancer risk; there was approximately 6% increase in risk per year; P = 3 × 10-14); increased risk with delayed menopause appeared to be mediated primarily by prolonged sex hormone exposure in a woman’s lifetime, not DDR mechanisms. This is the first study to confirm the link between early and late menopause and breast cancer risk using genetic information. Age at natural menopause genetic variants influence breast cancer risk primarily through variation in menopause timing. Although carrying higher numbers of ANM-increasing variants and enrichment in DDR genes are associated with a modest increase in breast cancer risk, the major mechanism for increased risk appears to be prolonged estrogen and/or progesterone exposure due to delayed menopause

Large-scale genomic analyses link reproductive aging to hypothalamic signaling, breast cancer susceptibility and BRCA1-mediated DNA repair

Copyright © 2015, Rights Managed by Nature Publishing GroupThis is the author's version of an article subsequently published in definitive form at: Nature Genetics (2015) doi:10.1038/ng.3412See supplementary documents for full affiliations and acknowledgmentsMenopause timing has a substantial impact on infertility and risk of disease, including breast cancer, but the underlying mechanisms are poorly understood. We report a dual strategy in ∼70,000 women to identify common and low-frequency protein-coding variation associated with age at natural menopause (ANM). We identified 44 regions with common variants, including two regions harboring additional rare missense alleles of large effect. We found enrichment of signals in or near genes involved in delayed puberty, highlighting the first molecular links between the onset and end of reproductive lifespan. Pathway analyses identified major association with DNA damage response (DDR) genes, including the first common coding variant in BRCA1 associated with any complex trait. Mendelian randomization analyses supported a causal effect of later ANM on breast cancer risk (∼6% increase in risk per year; P = 3 × 10(-14)), likely mediated by prolonged sex hormone exposure rather than DDR mechanisms

Genetic studies of body mass index yield new insights for obesity biology

Note: A full list of authors and affiliations appears at the end of the article. Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P 20% of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.</p