Electrocardiographic measures are indicative of the function of the cardiac conduction system. To search for sequence variants that modulate heart rate, PR interval and QRS duration in individuals of European descent, we performed a genome-wide association study in approximately 10,000 individuals and followed up the top signals in an additional approximately 10,000 individuals. We identified several genome-wide significant associations (with P < 1.6 x 10(-7)). We identified one locus for heart rate (MYH6), four for PR interval (TBX5, SCN10A, CAV1 and ARHGAP24) and four for QRS duration (TBX5, SCN10A, 6p21 and 10q21). We tested for association between these loci and subjects with selected arrhythmias in Icelandic and Norwegian case-control sample sets. We observed correlations between TBX5 and CAV1 and atrial fibrillation (P = 4.0 x 10(-5) and P = 0.00032, respectively), between TBX5 and advanced atrioventricular block (P = 0.0067), and between SCN10A and pacemaker implantation (P = 0.0029). We also replicated previously described associations with the QT interval.

We performed a genome-wide scan for sequence variants associating with atrial fibrillation in Iceland and followed up the most significant associations in samples from Iceland, Norway and USA. A sequence variant, rs7193343-T, in the ZFHX3 gene on chromosome 16q22 associated significantly with atrial fibrillation (combined OR=1.21, ). This variant also associates with ischemic

Objective: To investigate whether there is an association between serum thyroid-stimulating hormone (TSH) within the normal range and body mass index (BMI). Design and subjects: The study was performed in 6164 subjects (2813 males) who attended the fifth Tromsø study in 2001, and in 1867 subjects (873 males) that attended both the fourth Tromsø study in 1994/1995 as well as the fifth Tromsø study. Measurements: Height, weight, and serum TSH were measured in all subjects, and smoking status was recorded. Results: Smokers and nonsmokers were analyzed separately. In the fifth Tromsø study, serum TSH was positively and significantly associated with BMI in the nonsmokers. Within the normal TSH range (defined as the 2.5-97.5 percentile), nonsmoking males in the highest TSH quartile had a mean BMI 0.4 kg/m 2 higher compared to those in the lower quartile, whereas the difference for nonsmoking women was 1.4 kg/m 2 . Similarly, in nonsmokers in the longitudinal study, there was a significant and positive association between delta serum TSH (serum TSH in 2001 minus serum TSH in 1994) and delta BMI in those with serum TSH within the normal range both in 1994 and 2001. In these subjects, the quartile with the highest delta serum TSH had a mean increase in BMI from 1994 to 2001 that was 0.3 kg/m 2 higher compared to those in the quartile with the lowest delta serum TSH. For the smokers, relations between serum TSH and BMI were not statistically significant. Conclusion: In nonsmokers there is a positive association between serum TSH within the normal range and BMI.