Retinol Levels in Hashimoto's Thyroiditis

Hashimoto’s thyroiditis (HT) is one of the most common autoimmune diseases in the United States. Previous studies have proven that HT patients often have low vitamin D levels and benefit from vitamin D supplementation to help manage their autoimmune disease. Research is currently underway to investigate vitamin A’s benefits in the management of autoimmune diseases. Both of these vitamins have immune-modulating properties, and both affect thyroid function. This dissertation aims to establish whether HT patients had lower retinol (vitamin A) levels than participants that did not have HT. Data regarding retinol levels and thyroid function markers were gathered from a database of results from a small study conducted at Health Matters Clinic, in Northeast Arkansas. The study participants were sorted into two groups: HT and non-HT, and then 26 participants were randomly selected for each group. The HT group had participants that were positive for either or both thyroperoxidase and thyroglobulin antibodies, and that were not on thyroid medications such as levothyroxine. The non-HT group had participants that did not have thyroid autoantibodies, and did not have any other known autoimmune disease and had normal Thyroid Stimulating Hormone (TSH) levels. An independent sample t-test for differences in retinol levels was performed, as well as Pearson’s correlation for retinol and TSH and retinol and the anti-thyroid antibodies. The results revealed no statistical differences in retinol levels between the groups and no correlation between retinol and the level of thyroid antibodies. Retinol’s tight homeostatic control, which maintains steady serum levels regardless of liver reserve status, can explain the lack of statistical difference in retinol levels between the groups. A positive correlation was found between retinol and TSH levels (high TSH with high retinol), which may indicate some novel mechanism of retinol’s effect on the thyroid or retinol’s involvement in the etiology of HT, therefore, needs to be validated with more data. In conclusion, serum retinol levels do not appear to correlate with HT; in particular, serum retinol levels appear not to be decreased in patients with HT. At the same time, our data seem to indicate some involvement of retinol, or its signaling pathway, in thyroid disorders

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

No Evidence for Genome-Wide Interactions on Plasma Fibrinogen by Smoking, Alcohol Consumption and Body Mass Index : Results from Meta-Analyses of 80,607 Subjects

Peer reviewe

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

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

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

Characteristics at the time of fibrinogen measurement by study.

<p>BMI: body mass index.</p><p><i>* Mean (standard deviation).</i></p><p>Characteristics at the time of fibrinogen measurement by study.</p

Association of environmental factors with fibrinogen concentration (in g/L), adjusted for age and sex.

<p><b>A</b>) Forest plot for smoking status. The beta estimate with 95% confidence intervals indicates the change in mean fibrinogen concentration (in g/L) by smoking status for each study and across all studies (“overall”, estimated by meta-analysis). <b>B</b>) Forest plot for alcohol consumption. The beta estimate with 95% confidence intervals indicates the change in mean fibrinogen concentration (in g/L) by alcohol consumption for each study and across all studies (“overall”, estimated by meta-analysis). Alcohol consumption was assessed only in 20 studies. <b>C</b>) Forest plot for BMI. The beta estimate with 95% confidence intervals indicates the change in mean fibrinogen concentration (in g/L) by BMI for each study and across all studies (“overall”, estimated by meta-analysis).</p

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways