The epidemiologic link between schizophrenia (SCZ) and type 2 diabetes (T2D) remains poorly understood. Here, we investigate the presence and extent of a shared genetic background between SCZ and T2D using genome-wide approaches. We performed a genome-wide association study (GWAS) and polygenic risk score analysis in a Greek sample collection (GOMAP) comprising three patient groups: SCZ only (n = 924), T2D only (n = 822), comorbid SCZ and T2D (n = 505); samples from two separate Greek cohorts were used as population-based controls (n = 1,125). We used genome-wide summary statistics from two large-scale GWAS of SCZ and T2D from the PGC and DIAGRAM consortia, respectively, to perform genetic overlap analyses, including a regional colocalisation test. We show for the first time that patients with comorbid SCZ and T2D have a higher genetic predisposition to both disorders compared to controls. We identify five genomic regions with evidence of colocalising SCZ and T2D signals, three of which contain known loci for both diseases. We also observe a significant excess of shared association signals between SCZ and T2D at nine out of ten investigated p value thresholds. Finally, we identify 29 genes associated with both T2D and SCZ, several of which have been implicated in biological processes relevant to these disorders. Together our results demonstrate that the observed comorbidity between SCZ and T2D is at least in part due to shared genetic mechanisms.

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Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid diseases (AITD) characterized by progressive destruction of thyroid tissue that may lead to hypothyroidism. High thyroid autoantibodies against thyroid peroxidase (TPOAb) levels are present in 90% of patients with HT and serve as a clinical marker for the detection of early AITD/HT. The main aim of our study was to test whether recently identified genetic variants associated with TPOAb are also involved in HT development. A total of 504 unrelated individuals, including 200 patients with HT and 304 controls, were involved in this study. Diagnosis of HT cases was based on clinical examination, measurement of thyroid hormones (TSH and fT4) and antibodies (TgAb, TPOAb) and ultrasound examination. We selected and genotyped 14 known TPOAb-associated genetic variants. Case-control logistic regression model was used to test the association of selected genetic variants with HT. Additionally, we tested association of the same genetic variants with thyroid related quantitative traits (TPOAb levels, TgAb levels and thyroid gland volume) using linear regression. Three genetic variants showed nominal association with HT; rs10774625 in ATXN2 gene (p = 0.0149, OR = 0.73, CI = 0.56-0.94), rs7171171 near RASGRP1 gene (p = 0.0356, OR = 1.4, CI = 1.02-1.92) and rs11675434 in TPO gene (p = 0.041, OR = 1.31, CI = 1.01-1.69). Two of these SNPs (rs1077462, rs11675434) also showed association with TPOAb levels (p = 0.043, β = -0.39; p = 0.042, β = 0.40, respectively) and one (rs7171171) was associated with thyroid gland volume (p = 0.0226, β = -0.21). Our findings suggest that variants inside or near TPO, ATXN2 and RASGRP1 genes are associated with HT. Identified loci are novel to HT and represent good basis for further exploration of HT susceptibility.

Food is considered as important environmental factor that plays a role in development of Hashimoto's thyroiditis (HT). The goal of our study was to identify food groups, assessed by food frequency questionnaire, that differ in consumption frequency between 491 patients with HT and 433 controls. We also analysed association of food groups with the wealth of HT-related clinical traits and symptoms. We found significantly increased consumption of animal fat (OR 1.55, p < 0.0001) and processed meat (OR 1.16, p = 0.0012) in HT cases, whereas controls consumed significantly more frequently red meat (OR 0.80, p < 0.0001), non-alcoholic beverages (OR 0.82, p < 0.0001), whole grains (OR 0.82, p < 0.0001) and plant oil (OR 0.87, p < 0.0001). We also observed association of plant oil consumption with increased triiodothyronine levels in HT patients (β = 0.07, p < 0.0001), and, association of olive oil consumption with decreased systolic blood pressure (β = − 0.16, p = 0.001) in HT patients on levothyroxine (LT4) therapy. Analysis of food consumption between HT patients with and without LT4 therapy suggest that patients do not tend to modify their diet upon HT diagnosis in our population. Our study may be of relevance to nutritionists, nutritional therapists and clinicians involved in developing dietary recommendations for HT patients. Environmental factors, in addition to genetic factors, play important role in Hashimoto's thyroiditis (HT) development 1. HT is a chronic autoimmune thyroid disorder (AITD) characterized by the production of thyroid autoantibodies against thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) 2. Other main characteristics of HT include infiltration of lymphocytes and ruination of thyroid tissue, which usually leads to hypothyroidism 3. This disease predominantly affects female population and is considered as one of the most frequent endocrine disorders 4. The estimated incidence of HT is 350/100,000 for females and 80/100,000 per year for males 5. It is most often diagnosed in women between the age of 30 and 60 6. High iodine intake (median urinary iodine concentration ≥ 300 μg/L) 7 , especially in areas with sufficient iodine supply, is one of the most known factors that increase the incidence of HT 8. Also, low vitamin D levels (below 30 ng/mL) 9 and low selenium intake (bellow 40 µg/day) 10 are proposed to be risk factors for HT development, albeit a role of these factors in HT still needs to be confirmed. Conversely, alcohol intake was proposed to decrease the risk for HT 11. Other dietary factors are also considered as potential environmental modifiers of the clinical appearance of HT 12-15. A diet low in gluten has been recently proposed to have beneficial effects on the disease course in a study of 34 women with HT 13. Another study of 83 patients with HT indicated that restriction of lactose intake in lactose-intolerant HT patients resulted with decreased thyroid-stimulating hormone (TSH) levels 14. However, the current knowledge of this topic is scarce and only the following two studies ...

Background: Hashimoto's thyroiditis (HT) is the most common form of autoimmune thyroid disorders characterized by lower production of thyroid hormones and positivity to autoantibodies to thyroglobulin (TgAb) and/or thyroid peroxidase (TPOAb). We performed a comprehensive phenotypic characterization of patients with HT, with specific focus on thyroid autoimmunity, to get better understanding of disease manifestation. Methods: We collected information on thyroid-specific phenotypes (TSH, T3, T4, fT4, TgAb, TPOAb, thyroid volume) and other clinical phenotypes (age, body surface area, number of hypothyroidism symptoms, blood pressure) from 290 patients with HT without levothyroxine (LT4) therapy with the aim to test for correlations between thyroid-specific and clinical phenotypes. Results: Our key and novel finding is the existence of significant positive correlation between TgAb levels and the number of symptoms (r = 0.25, p = 0.0001) in HT patients without LT4 therapy that remained significant after adjustment for TPOAb, T3, TSH levels and thyroid volume (β = 0.66, SE = 0.3, p = 0.0299). Increased TgAb levels are significantly associated with fragile hair (p = 0.0043), face edema (p = 0.0061), edema of the eyes (p = 0.0293) and harsh voice (p = 0.0349). Conclusions: Elevated TgAb levels are associated with symptom burden in HT patients, suggesting a role of thyroid autoimmunity in clinical manifestations of HT. Based on these results, we recommend screening for TgAb antibodies in HT patients with symptom burden. We also suggest that further work on understandings of symptoms appearance due to their autoimmune or hypothyroid causation is needed.