FLT3 stop mutation increases FLT3 ligand level and risk of autoimmune thyroid disease.

Autoimmune thyroid disease is the most common autoimmune disease and is highly heritable. Here, by using a genome-wide association study of 30,234 cases and 725,172 controls from Iceland and the UK Biobank, we find 99 sequence variants at 93 loci, of which 84 variants are previously unreported. A low-frequency (1.

The number of adults with incident type 1 diabetes phenotype in Iceland is half the number in children - A population based study.

Aims: Type1 diabetes is generally regarded as an abruptly presenting disease in children without family history. The incidence and prevalence of insulin requiring diabetes in adults is unclear. The aim of this study was to clarify this issue by examining the epidemiology of type 1 diabetes diagnosed in adulthood in a countrýs whole population.

Sequence variants associating with urinary biomarkers.

Urine dipstick tests are widely used in routine medical care to diagnose kidney and urinary tract and metabolic diseases. Several environmental factors are known to affect the test results, whereas the effects of genetic diversity are largely unknown. We tested 32.

Effect of sequence variants on variance in glucose levels predicts type 2 diabetes risk and accounts for heritability.

Sequence variants that affect mean fasting glucose levels do not necessarily affect risk for type 2 diabetes (T2D). We assessed the effects of 36 reported glucose-associated sequence variants on between- and within-subject variance in fasting glucose levels in 69,142 Icelanders. The variant in TCF7L2 that increases fasting glucose levels increases between-subject variance (5.

An Expanded Genome-Wide Association Study of Type 2 Diabetes in Europeans.

To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci ( < 5 × 10), including variants near the , , and genes.

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation.

Loss-of-function mutations in SLC30A8 protect against type 2 diabetes.

Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D). Through sequencing or genotyping of ~150,000 individuals across 5 ancestry groups, we identified 12 rare protein-truncating variants in SLC30A8, which encodes an islet zinc transporter (ZnT8) and harbors a common variant (p.Trp325Arg) associated with T2D risk and glucose and proinsulin levels.

Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci.

Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes.

Through whole-genome sequencing of 2,630 Icelanders and imputation into 11,114 Icelandic cases and 267,140 controls followed by testing in Danish and Iranian samples, we discovered 4 previously unreported variants affecting risk of type 2 diabetes (T2D). A low-frequency (1.47%) variant in intron 1 of CCND2, rs76895963[G], reduces risk of T2D by half (odds ratio (OR) = 0.

Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes.

To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genome-wide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D.

Parental origin of sequence variants associated with complex diseases.

Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined.

Risk of retinal neovascularization in the second eye in patients with proliferative diabetic retinopathy.

Purpose: This study aimed to evaluate the risk of proliferative diabetic retinopathy (DR) in the fellow eye of an eye with existing proliferative DR.

Methods: Our DR screening programme database listed 1513 diabetes patients alive at the time of the study. Seventy-six had proliferative DR in one or both eyes.

Association of genetic variants at 3q22 with nephropathy in patients with type 1 diabetes mellitus.

Diabetic nephropathy (DN) is the primary cause of morbidity and mortality in patients with type 1 diabetes mellitus (T1DM) and affects about 30% of these patients. We have previously localized a DN locus on chromosome 3q with suggestive linkage in Finnish individuals. Linkage to this region has also been reported earlier by several other groups.

Evaluating iodine deficiency in pregnant women and young infants-complex physiology with a risk of misinterpretation.

Objective: To review methods for evaluating iodine deficiency in pregnant women and young infants and to discuss factors to be considered in the interpretation of their results.

Design: Review of the literature regarding the various methods available for assessing iodine status.

Setting: Population surveys and research studies.

[Treatment pattern and results in an outpatient population with type 2 diabetes in Iceland.].

Aims: Type 2 diabetes mellitus is a major health problem all over the world. The prevalence of the disease is increasing markedly. Healthcare cost associated with type 2 diabetes is high and the long-term diabetic complications account for the greatest proportion of direct cost.

Defective prevention of immune precipitation in autoimmune diseases is independent of C4A*Q0.

Increased prevalence of C4 null alleles is a common feature of autoimmune diseases. We have shown previously that complement-dependent prevention of immune precipitation (PIP) is defective in patients with systemic lupus erythematosus (SLE), and correlated this defect with C4A*Q0 and low levels of the C4A isotype. To further clarify the role of C4A in the aetiology of SLE, we now extend our studies to other diseases which have been associated with C4A*Q0.

Unchanged incidence of diabetic nephropathy in Type 1 diabetes: a nation-wide study in Iceland.

Aims: Diabetic nephropathy is an uncommon cause of end-stage renal disease in Iceland in contrast to most industrialized countries. The aim of this study was to examine the incidence of diabetic nephropathy in Iceland.

Methods: All patients diagnosed with Type 1 diabetes in Iceland before 1992 were studied retrospectively.

Dose titration of repaglinide in patients with inadequately controlled type 2 diabetes.

A total of 385 drug-therapy naïve patients, with inadequately controlled type 2 diabetes, were randomised into a multinational, parallel-group study to compare two strategies for dose titration of the oral hypoglycaemic agent repaglinide. Patients were allocated to either a fasting blood glucose (FBG) monitoring group with titration target 4.4-6.

MODY in Iceland is associated with mutations in HNF-1alpha and a novel mutation in NeuroD1.

Aims/hypothesis: Five different types of maturity-onset diabetes of the young (MODY) have been identified until now but mutation screening suggests that more MODY genes exist. Mutations in genes encoding transcription factors essential for normal development and function of pancreatic beta cells has recently become important in studying the genetics of Type II (non-insulin-dependent) diabetes mellitus. Patients with MODY and their families in Iceland were screened for mutations in the transcription factor genes.

Thyroid disorders in mild iodine deficiency.

Comparative epidemiologic studies in areas with low and high iodine intake and controlled studies of iodine supplementation have demonstrated that the major consequence of mild-to-moderate iodine deficiency for the health of the population is an extraordinarily high occurrence of hyperthyroidism in elderly subjects, especially women, with risk of cardiac arrhythmias, osteoporosis, and muscle wasting. The hyperthyroidism is caused by autonomous nodular growth and function of the thyroid gland and it is accompanied by a high frequency of goiter. Pregnant women and small children are not immediately endangered but the consequences of severe iodine deficiency for brain development are grave and a considerable safety margin is advisable.

Iodine intake and the pattern of thyroid disorders: a comparative epidemiological study of thyroid abnormalities in the elderly in Iceland and in Jutland, Denmark.

Thyroid abnormalities are common in all populations, but it is difficult to compare results of epidemiological studies, because different methods have been used for evaluation. We studied the importance of the population iodine intake level for the prevalence rate of various thyroid abnormalities in elderly subjects. Random samples of elderly subjects (68 yr) were selected from the central person registers in Jutland, Denmark, with low (n = 423) and, in Iceland, with longstanding relatively high (n = 100) iodine intake.

Prevalence and incidence of NIDDM in Iceland: evidence for stable incidence among males and females 1967-1991--the Reykjavik Study.

This is the first large survey carried out in Iceland to estimate the prevalence and incidence of known and unknown non-insulin-dependent (Type 2) diabetes (NIDDM) among males and females, aged 34-79. The population in this survey was 9128 males and 9759 females born between 1907 and 1935 and examined in the prospective Reykjavik Study 1967-1991. Participants were invited from one to five times during the 24 years.

[Autonomic nervous dysfunction in insulin-dependent (type 1) diabetic men.].

The development of autonomic nervous dysfunction (AND) in subjects with diabetes influences life expectancy and may cause sudden death. The present study evaluates disturbances of AND in 41 men with type 1 diabetes mellitus, but without heart symptoms, and the relationship with other long term diabetic complications and blood sugar control. Their age ranged 18-50 years (mean 34 +/-8 years) and the duration of diabetes 1-43 years (mean 13 +/-10 years).