scholarly journals A method for identifying genetic heterogeneity within phenotypically-defined disease subgroups

2016 ◽  
Author(s):  
James Liley ◽  
John A Todd ◽  
Chris Wallace
Keyword(s):  
Genetic Variants ◽  
Genetic Architecture ◽  
Effect Sizes ◽  
Thyroid Peroxidase ◽  
Global Test ◽  
Genome Wide ◽  
Thyroid Peroxidase Antibody ◽  
Antibody Positivity ◽  
Post Hoc

AbstractMany common diseases show wide phenotypic variation. We present a statistical method for determining whether phenotypically defined subgroups of disease cases represent different genetic architectures, in which disease-associated variants have different effect sizes in the two subgroups. Our method models the genome-wide distributions of genetic association statistics with mixture Gaussians. We apply a global test without requiring explicit identification of disease-associated variants, thus maximising power in comparison to a standard variant by variant subgroup analysis. Where evidence for genetic subgrouping is found, we present methods for post-hoc identification of the contributing genetic variants.We demonstrate the method on a range of simulated and test datasets where expected results are already known. We investigate subgroups of type 1 diabetes (T1D) cases defined by autoantibody positivity, establishing evidence for differential genetic architecture with thyroid peroxidase antibody positivity, driven generally by variants in known T1D associated regions.

scholarly journals Circulating Betatrophin Is Increased in Patients with Overt and Subclinical Hypothyroidism

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Cheng Han ◽  
Xinghai Xia ◽  
Aihua Liu ◽  
Xiaowen Zhang ◽  
Mi Zhou ◽  
...  
Keyword(s):  
Subclinical Hypothyroidism ◽  
Thyroid Dysfunction ◽  
Metabolic Diseases ◽  
Thyroid Autoimmunity ◽  
Thyroid Stimulating Hormone ◽  
Overt Hypothyroidism ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibody ◽  
Antibody Positivity ◽  
Healthy Control

Thyroid hormone (TH) affects many metabolic processes such as promoting oxidation of sugar, fat, and protein in many tissues. Thyroid dysfunction is associated with metabolic disorders. The newly discovered adipocyte- and hepatocyte-derived cytokine, betatrophin, has been reported to be involved in metabolic diseases, but its influence on thyroid dysfunction is uncertain. Therefore, the present study aims to evaluate circulating betatrophin levels in subjects with different thyroid function status and to predict the factors associated with betatrophin levels, especially whether thyroid stimulating hormone (TSH), TH, or thyroid autoantibodies are associated with betatrophin levels. In the study, serum betatrophin was measured in the subjects grouped as overt hypothyroidism (OH), subclinical hypothyroidism (SCH), euthyroid with isolated thyroid peroxidase antibody positivity (isolated Ab), and healthy control (HC), according to their thyroid functions. From our results, we found that betatrophin may be associated with thyroid insufficiency but not thyroid autoimmunity. Thus, when interpreting the results of betatrophin, thyroid functions should also be taken into consideration.

scholarly journals The distribution of common-variant effect sizes

2020 ◽  
Author(s):  
Luke Jen O’Connor
Keyword(s):  
Sample Size ◽  
Size Distribution ◽  
Effect Size ◽  
Genetic Architecture ◽  
Common Variant ◽  
Effect Sizes ◽  
Summary Statistics ◽  
Genome Wide ◽  
Variant Effect ◽  
Effect Size Distribution

AbstractThe genetic effect-size distribution describes the number of variants that affect disease risk and the range of their effect sizes. Accurate estimates of this distribution would provide insights into genetic architecture and set sample-size targets for future genome-wide association studies. We developed Fourier Mixture Regression (FMR) to estimate common-variant effect-size distributions from GWAS summary statistics. We validated FMR in simulations and in analyses of UK Biobank data, using interim-release summary statistics (max N=145k) to predict the results of the full release (N=460k). Analyzing summary statistics for 10 diseases (avg Neff=169k) and 22 other traits, we estimated the sample size required for genome-wide significant SNPs to explain 50% of SNP-heritability. For most diseases the requisite number of cases is 100k-1M, an attainable number; ten times more would be required to explain 90% of heritability. In well-powered GWAS, genome-wide significance is a conservative threshold, and loci at less stringent thresholds have true positive rates that remain close to 1 if confounding is controlled. Analyzing the shape of the effect-size distribution, we estimate that heritability accumulates across many thousands of SNPs with a wide range of effect sizes: the largest effects (at the 90th percentile of heritability) are 100 times larger than the smallest (10th percentile), and while the midpoint of this range varies across traits, its size is similar. These results suggest attainable sample size targets for future GWAS, and they underscore the complexity of genetic architecture.

scholarly journals SAT-230 Newly Diagnosed Schmidt’s Syndrome and Steroid Induced Psychosis

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Myat Han Soe
Keyword(s):  
Type 1 Diabetes ◽  
Glucocorticoid Receptors ◽  
Lymphocytic Infiltration ◽  
Thyroid Peroxidase ◽  
Autoimmune Polyendocrine Syndrome ◽  
Thyroid Peroxidase Antibody ◽  
Lab Test ◽  
Schmidt’S Syndrome

Abstract In 1926, Schmidt reported the combination of hypothyroidism and adrenal insufficiency (AI) with lymphocytic infiltration of both the thyroid and adrenal glands.1 This syndrome is now known as autoimmune polyendocrine syndrome (APS) type 2, characterized by two of the following three endocrinopathies: type 1 diabetes, autoimmune thyroiditis, and Addison’s disease.2 It may seem surprising that transient relative hypercortisolemia in AI patients at the beginning of treatment results in steroid induced psychosis (SIP). Here, we present a patient who developed SIP after starting steroid for AI. 44 year old Caucasian female with bipolar disorder and Hashimoto’s thyroiditis was admitted for generalized weakness, nausea, vomiting and weight loss of about 15 pounds in 3 months. On exam, blood pressure was 93/54 mmHg and pulse rate was 99. Her abdomen and arms looked hyperpigmented. Lab test revealed plasma glucose of 68 mg/dl, serum sodium of 129 mmol/l (133-145), potassium of 4.9 mmol/l (3.6 – 5.2), bicarbonate of 20 mmol/l (22 – 29). TSH was 16.93 mIU/ml (0.4 – 4.00) and FT4 was 0.74 ng/dl (0.7 1.8). CT abdomen and pelvis with contrast was unremarkable. As AI was suspected, cortisol level was checked and low at 0.5ug/dl. Cosyntropin stimulation test (CST) revealed pre-CST cortisol of 0.4 ug/dl, and post CST cortisol of 0.5 ug/dl at 45 min. ACTH was elevated at 514.4 pg/ml (7.2 – 63.3). A diagnosis of Schmidt’s syndrome was made based on elevated 21 hydroxylase of 8.5 U/ml (<1.0) and anti-thyroid peroxidase antibody of 20.5IU/ml (<5.6). Screening for type 1 diabetes and celiac disease was negative. After CST, stress dose hydrocortisone was started and dose was gradually tapered down in a few days. However, five days after steroid therapy, patient was admitted for suicidal ideation and catatonia which resolved quickly with Ativan and steroid taper to physiologic dose. APS type 2 has a prevalence of 1:1000. Clinicians should raise the suspicion for this syndrome in the appropriate context as seen in this patient presenting with classic features of AI. Although SIP in AI patients is not frequently reported, we should be mindful about this potential event especially in patients with underlying psychiatric illness. It is postulated that prolonged hypocortisolism in undiagnosed AI might lead to upregulation of central glucocorticoid receptors and hence glucocorticoid replacement might elicit a relative supraphysiological response in these patients.3

scholarly journals Prevalence of thyroid dysfunction and anti-thyroid peroxidase antibodies in vitiligo patients

2017 ◽  
Vol 3 (1) ◽  
pp. 140 ◽  
Author(s):  
Jishna P. ◽  
M. P. Binitha ◽  
Abdul Latheef E. N. ◽  
V. P. Anilakumari
Keyword(s):  
Autoimmune Diseases ◽  
Thyroid Dysfunction ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Cross Sectional ◽  
Autoimmune Thyroid ◽  
Thyroid Peroxidase Antibodies ◽  
Thyroid Peroxidase Antibody ◽  
Antibody Positivity ◽  
Antibody Levels

<p class="abstract"><strong>Background:</strong> Vitiligo is associated with various autoimmune diseases, including autoimmune thyroid disease. The objectives of the present study was to determine the prevalence of thyroid dysfunction and anti-thyroid peroxidase antibodies in patients with vitiligo, and to compare the clinical profile of anti-thyroid peroxidase positive and anti-thyroid peroxidase negative patients<span lang="EN-IN">.</span></p><p class="abstract"><strong>Methods:</strong> A cross-sectional comparative study was conducted in 100 patients with vitiligo and 100 controls. After dermatologic and systemic evaluation, serum thyroid hormones and anti-thyroid peroxidase antibody levels were measured in all the subjects.<strong></strong></p><p class="abstract"><strong>Results:</strong> Thyroid dysfunction was more common in the vitiligo group (27%) than in the controls. Serum thyroid stimulating hormone abnormalities were more common in the vitiligo group (27%) than in the controls (6%). The most common thyroid dysfunction was subclinical hypothyroidism. Anti-thyroid peroxidase antibody positivity was higher in the vitiligo group (36%) when compared to the controls (24%), and the most common type of vitiligo was vitiligo vulgaris (18%) in this group. Thyroid dysfunction and anti-thyroid peroxidase positivity were more common in women (58%) when compared to men (42%). There was a significantly higher prevalence of other autoimmune diseases in the vitiligo group (20%) compared to the controls (6%)<span lang="EN-IN">. </span></p><p class="abstract"><strong>Conclusions:</strong> This study shows a significant association between vitiligo and thyroid dysfunction, anti-thyroid peroxidase antibodies and other autoimmune diseases. We recommend that thyroid evaluation and regular follow-up should be done in patients with vitiligo for prompt detection of thyroid dysfunction<span lang="EN-IN">.</span></p>

scholarly journals Anti-Thyroid Peroxidase Antibody in Vitiligo: A Prevalence Study

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
R. Dash ◽  
A. Mohapatra ◽  
B. S. Manjunathswamy
Keyword(s):  
Thyroid Disease ◽  
Demographic Data ◽  
Thyroid Autoimmunity ◽  
Cross Sectional Study ◽  
Thyroid Peroxidase ◽  
Cross Sectional ◽  
Thyroid Peroxidase Antibody ◽  
Number Of Patients ◽  
Antibody Positivity ◽  
Time Of Presentation

Aim.The aim of the study was to study the relation of vitiligo with demographic data like age, sex, and duration and determine the prevalence of thyroid autoimmunity in vitiligo patients.Materials and Methods.This study was a cross sectional study consisting of 100 patients clinically diagnosed (old and new) as having vitiligo irrespective of age or sex. Patients with known thyroid disease on supplementation therapy, or who had undergone thyroid surgery, those on antithyroid medication, patients with other causes of leukoderma, and cases who do not provide informed consent were excluded from the study. Serum TSH and anti-TPO antibodies were measured in all the patients.Results.The prevalence of anti-TPO antibody positivity was found to be 28%.Conclusion.According to our study, none of our vitiligo patients had symptoms or signs of thyroid disease at the time of presentation but, on biochemical evaluation, anti-TPO antibodies were found in a considerable number of patients. Hence, we recommend screening of these patients with thyroid antibodies.

206: An evaluation of risk-factor based screening for thyroid peroxidase antibody positivity in pregnancy

2009 ◽  
Vol 201 (6) ◽  
pp. S89
Author(s):  
Paola Aghajanian ◽  
Carole A. Spencer ◽  
Richard H. Lee ◽  
Melissa L. Wilson ◽  
Thomas M. Goodwin ◽  
...  
Keyword(s):  
Risk Factor ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibody ◽  
Antibody Positivity ◽  
In Pregnancy
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