Eine Analyse von Alphabetisierungsmaterialien für Erwachsene im DaZ-Unterricht

Zehn Alphabetisierungsmaterialien bzw. -lehrwerke werden hinsichtlich Buchstabenprogression, Sprachvermittlung (Grammatik, Wortschaftz, Lexik, Phonetik, Fertigkeiten), Layout und Interkulturalität analysiert und bewertet

Identification of Novel Genetic Loci Associated with Thyroid Peroxidase Antibodies and Clinical Thyroid Disease

Peer reviewe

Identification of novel genetic Loci associated with thyroid peroxidase antibodies and clinical thyroid disease.

Autoimmune thyroid diseases (AITD) are common, affecting 2-5% of the general population. Individuals with positive thyroid peroxidase antibodies (TPOAbs) have an increased risk of autoimmune hypothyroidism (Hashimotos thyroiditis), as well as autoimmune hyperthyroidism (Graves disease). As the possible causative genes of TPOAbs and AITD remain largely unknown, we performed GWAS meta-analyses in 18,297 individuals for TPOAb-positivity (1769 TPOAb-positives and 16,528 TPOAb-negatives) and in 12,353 individuals for TPOAb serum levels, with replication in 8,990 individuals. Significant associations (P<5×10(-8)) were detected at TPO-rs11675434, ATXN2-rs653178, and BACH2-rs10944479 for TPOAb-positivity, and at TPO-rs11675434, MAGI3-rs1230666, and KALRN-rs2010099 for TPOAb levels. Individual and combined effects (genetic risk scores) of these variants on (subclinical) hypo- and hyperthyroidism, goiter and thyroid cancer were studied. Individuals with a high genetic risk score had, besides an increased risk of TPOAb-positivity (OR: 2.18, 95% CI 1.68-2.81, P = 8.1×10(-8)), a higher risk of increased thyroid-stimulating hormone levels (OR: 1.51, 95% CI 1.26-1.82, P = 2.9×10(-6)), as well as a decreased risk of goiter (OR: 0.77, 95% CI 0.66-0.89, P = 6.5×10(-4)). The MAGI3 and BACH2 variants were associated with an increased risk of hyperthyroidism, which was replicated in an independent cohort of patients with Graves disease (OR: 1.37, 95% CI 1.22-1.54, P = 1.2×10(-7) and OR: 1.25, 95% CI 1.12-1.39, P = 6.2×10(-5)). The MAGI3 variant was also associated with an increased risk of hypothyroidism (OR: 1.57, 95% CI 1.18-2.10, P = 1.9×10(-3)). This first GWAS meta-analysis for TPOAbs identified five newly associated loci, three of which were also associated with clinical thyroid disease. With these markers we identified a large subgroup in the general population with a substantially increased risk of TPOAbs. The results provide insight into why individuals with thyroid autoimmunity do or do not eventually develop thyroid disease, and these markers may therefore predict which TPOAb-positives are particularly at risk of developing clinical thyroid dysfunction

Genetic risk score and the risk of TPOAb-positivity.

<p>GRS, genetic risk score (based on rs11675434, rs653178, rs10944479, rs1230666, rs2010099).</p>a<p>Adjusted for age and gender</p

Population characteristics and serum TPOAb, TSH, and FT4 level measurements specifications.

<p>Population characteristics and serum TPOAb, TSH, and FT4 level measurements specifications.</p

Newly identified loci associated with TPOAb-positivity and/or serum TPOAb levels reaching genome wide significance.

<p>Chr., chromosome</p>a<p>Risk allele frequency: Weighted mean frequency of the risk allele across all included cohorts.</p>b<p>Adjusted for age and gender</p>c<p>Expressed in sd of natural logarithm transformed serum TPOAb level, adjusted for age and gender</p

Newly identified TPOAb associated loci and the risk of thyroid disease in stage 1 and 2 populations.

<p>All analyses adjusted for age and gender.</p><p><i>ATXN2</i>-rs653178 is in high LD with <i>SH2B3-</i> rs3184504</p><p><i>MAGI3-</i>rs1230666 is in high LD with <i>PTPN22-</i>rs2476601</p

Newly identified TPOAb associated loci, genetic risk scores and the risk of goiter.

<p>GRS, genetic risk score (based on rs11675434, rs653178, rs10944479, rs1230666, rs2010099).</p>a<p>Adjusted for age, gender, and body surface area.</p><p><i>ATXN2</i>-rs653178 is in high LD with <i>SH2B3</i>-rs3184504.</p><p><i>MAGI3</i>-rs1230666 is in high LD with <i>PTPN22</i>-rs24756601.</p