Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

Objective-To investigate the clinical features and natural history of mal de debarquement (MdD).Design-Retrospective case review with follow-up questionnaire and telephone interviews. Setting-University Neurotology Clinic.Patients-Patients seen between 1980 and 2006 who developed a persistent sensation of rocking or swaying for at least 3 days after exposure to passive motion.Main outcome measure-Clinical features, diagnostic testing, and questionnaire responses.Results-Of 64 patients (75 % women) identified with MdD, 34 completed follow-up questionnaires and interviews in 2006. Most patients had normal neurological exams, ENGs and brain MRIs. The average age of the first MdD episode was 39 ± 13 years. A total of 206 episodes were experienced by 64 patients. Of these, 104 episodes (51 %) lasted > 1 month; 18 %, > 1 year; 15 %, > 2 years; 12 %, > 4 years, and 11 %, > 5 years. Eighteen patients (28 %) subsequently developed spontaneous episodes of MdD-like symptoms after the initial MdD episode. There was a much higher rate of migraine in patients who went on to develop spontaneous episodes (73 %) than in those who did not (22 %). Subsequent episodes were longer than earlier ones in most patients who had multiple episodes. Re-exposure to passive motion temporarily decreased symptoms in most patients (66 %). Subjective intolerance to visual motion increased (10 % to 66 %) but self-motion sensitivity did not (37 % to 50 %) with onset of MdD.Conclusion-The majority of MdD episodes lasting longer than 3 days resolve in less than one year but the probability of resolution declines each year. Many patients experience multiple MdD episodes. Some patients develop spontaneous episodes after the initial motion-triggered episode with migraine being a risk factor.

Age of onset of episodic vertigo or fluctuating hearing loss was significantly lower in patients with MMD (mean +/- 1.96*SE = 37.2 +/- 6.3 years) than in those with MD (mean +/- 1.96*SE = 49.3 +/- 4.4 years). Concurrent bilateral aural symptoms and hearing loss were seen in 56% of MMD and 4% of MD patients. A family history of episodic vertigo was seen in 39% of MMD and 2% of MD patients.

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