Knut Hagen

Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 × 10−9, odds ratio = 1.23, 95% CI 1.150–1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 × 10−11 (odds ratio = 1.18, 95% CI 1.127–1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 × 10−5, permuted threshold for genome-wide significance 7.7 × 10−5). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.

The impact of body mass index on the prevalence of low back pain: the HUNT study.

Study Design. A cross-sectional population-based study. Objective. To examine the association between body mass index and chronic low back pain, with adjustment for potential confounders. Summary of Background Data. Although many studies have investigated this association, it is still unclear whether there is a general relationship between body mass index and low back pain which applies to all populations. Methods. This study is based on data collected in the HUNT 2 study in the county of Nord-Trøndelag in Norway between 1995 and 1997. Among a total of 92,936 persons eligible for participation, 30,102 men and 33,866 women gave information on body mass index and indicated whether they suffered from chronic low back pain (69% participation rate). A total of 6293 men (20.9%) and 8923 women (26.3%) experienced chronic low back pain. Relations were assessed by logistic regression of low back pain with respect to body mass index and other variables. Results. In both sexes, a high body mass index was significantly associated with an increased prevalence of low back pain. In men the estimated OR per 5 kg/m2 increase in body mass index was 1.07 (95% CI: 1.03–1.12) and in women 1.17 (95% CI: 1.14–1.21), after adjustment for age, with a significantly stronger association in women. Additional adjustment for education, smoking status, leisure time physical activity, employment status, and activity at work hardly affected these associations. No interactions were found with most other factors. Conclusion. This large population-based study indicates that obesity is associated with a high prevalence of low back pain. Further studies are needed to determine if the association is causal.

Is Headache Related to Asthma, Hay Fever, and Chronic Bronchitis? The Head-HUNT Study

Objectives.—To examine the relationship between migraine and nonmigrainous headache and asthma, hay fever, and chronic bronchitis in a large cross‐sectional population‐based study.

Body mass index as a risk factor for developing chronic low back pain: a follow-up in the Nord-Trøndelag Health Study.

Study Design. A population-based, prospective cohort study. Objective. To determine whether overweight, obesity, or more generally an elevated body mass index (BMI) increase the probability of experiencing chronic low back pain (LBP) after an 11-year period, both among participants with and without LBP at baseline. Summary of Background Data. Chronic LBP is a common disabling disorder in modern society. Cross-sectional studies suggest an association between an elevated BMI and LBP, but it is not clear whether this is a causal relationship. Methods. Data were obtained from the community-based HUNT 2 (1995–1997) and HUNT 3 (2006–2008) studies of an entire Norwegian county. Participants were 8733 men and 10,149 women, aged 30 to 69 years, who did not have chronic LBP at baseline, and 2669 men and 3899 women with LBP at baseline. After 11 years, both groups indicated whether they currently had chronic LBP, defined as pain persisting for at least 3 months continuously during the last year. Results. A significant positive association was found between BMI and risk of LBP among persons without LBP at baseline. The odds ratio for BMI 30 or more versus BMI less than 25 was 1.34 (95% confidence interval [CI], 1.08–1.67) for men and 1.22 (95% CI, 1.03–1.46) for women, in analyses adjusted for age, education, work status, physical activity at work and in leisure time, smoking, blood pressure, and serum lipid levels. A significant positive association was also established between BMI and recurrence of LBP among women. LBP status at baseline had negligible influence on subsequent change in BMI. Conclusion. High values of BMI may predispose to chronic LBP 11 years later, both in individuals with and without LBP. The association between BMI and LBP is not explained by an effect of LBP on later change in BMI.

Physical inactivity is associated with chronic musculoskeletal complaints 11 years later: results from the Nord-Trøndelag Health Study

BackgroundPhysical inactivity is associated with several diseases, but studies evaluating the association between chronic musculoskeletal complaints (MSCs) and physical exercise have shown conflicting results. The aim of this large-scale prospective population-based study was to investigate the association between self-reported physical exercise at baseline and the prevalence of chronic musculoskeletal complaints (MSCs) 11 years later.MethodsThe results are based upon two consecutive public health studies conducted within the county of Nord-Trøndelag, Norway (The HUNT studies). A total of 39,520 (83%) out of 47,556 adults who participated in HUNT 1 and HUNT 2 responded to questions about physical exercise at baseline in 1984–86, and to questions about musculoskeletal complaints 11 years later (1995–97). Chronic MSCs was defined as MSCs ≥ 3 months during the past year, and chronic widespread MSCs such as pain ≥ 15 days during the last month from the axial region, above the waist, and below the waist. Associations were assessed using multiple logistic regression, estimating prevalence odds ratio (OR) with 95% confidence intervals (CIs). All the final analyses were adjusted for age, gender, body mass index, smoking and education level.ResultsAt follow-up 20,223 (51%) reported chronic MSCs, and among these 2,318 (5.9%) reported chronic widespread MSCs. Individuals who exercised at baseline were less likely to report chronic MSCs 11 years later (OR 0.91, 95% CI 0.85–0.97) than inactive persons. Among individuals who exercised more than three times per week, chronic widespread MSCs were 28% less common (OR 0.72, 95% CI 0.59–0.88) compared to inactive individuals.ConclusionIn this large-scale population-based study, physical exercise was associated with lower prevalence of chronic MSCs, in particular chronic widespread MSCs. Future studies should try to clarify whether chronic MSCs are a cause or a consequence of inactivity.

Prevalence, burden, and cost of headache disorders

Purpose of reviewDocumentation of disease impact, both on the individual and on society, is vital to ensure that healthcare resources are distributed according to the relative importance of the different disorders. For headache, international initiatives now promote the cause of headache sufferers by documenting the prevalence, burden, and cost. The present review aims to give an update on studies on these aspects of headache that have appeared since 2004. Recent findingsSome studies indicate that the headache prevalence may be increasing, but the evidence is conflicting. The disease burden and the costs of migraine are probably among the highest for the neurologic disorders, and it is probably as high in poor countries as in the rich. For other headaches, reliable data on impact are still scarce, but these disorders may be as important as migraine because they are even more prevalent. SummaryRobust and increasing evidence suggests that headache should be taken seriously as a public health problem, not only in the rich countries. More studies on the impact of nonmigrainous headaches, largely of the tension type, are urgently needed for a full evaluation of the consequences of headache disorders.

Risk factors for medication-overuse headache: An 11-year follow-up study. The Nord-Trøndelag Health Studies

Summary Several risk factors for medication overuse headache did not increase the risk for chronic daily headache without overuse, which suggests they are distinct disorders. ABSTRACT Medication‐overuse headache (MOH) is relatively common, but its incidence has not been calculated and there are no prospective population‐based studies that have evaluated risk factors for developing MOH. The aim of this study was to estimate incidences of and identify risk factors for developing chronic daily headache (CDH) and MOH. This longitudinal population‐based cohort study used data from the Nord‐Trøndelag Health Surveys performed in 1995–1997 and 2006–2008. Among the 51,383 participants at baseline, 41,766 were eligible approximately 11 years later. There were 26,197 participants (responder rate 63%), among whom 25,596 did not report CDH at baseline in 1995–1997. Of these, 201 (0.8%) had MOH and 246 (1.0%) had CDH without medication overuse (CDHwoO) 11 years later. The incidence of MOH was 0.72 per 1000 person‐years (95% confidence interval 0.62–0.81). In the multivariate analyses, a 5‐fold risk for developing MOH was found among individuals who at baseline reported regular use of tranquilizers [odds ratio 5.2 (3.0–9.0)] or who had a combination of chronic musculoskeletal complaints, gastrointestinal complaints, and Hospital Anxiety and Depression Scale score ⩾11 [odds ratio 4.7 (2.4–9.0)]. Smoking and physical inactivity more than doubled the risk of MOH. In contrast, these factors did not increase the risk of CDHwoO. In this large population‐based 11‐year follow‐up study, several risk factors for MOH did not increase the risk for CDHwoO, suggesting these are pathogenetically distinct. If the noted associations are causal, more focus on comorbid condition, physical activity, and use of tobacco and tranquilizers may limit the development of MOH.

Time trends in the prevalence of headache disorders. The Nord-Trøndelag Health Studies (HUNT 2 and HUNT 3):

Earlier reports regarding secular trends of migraine are conflicting, and there is a lack of long-term follow-up studies of other headache syndromes among adults. The aim of the present study was to assess any changes in the prevalence of the major headache types in a large adult population. With an 11-year interval, all inhabitants aged ≥20 years (n = 92,566 and 94,194) in the Norwegian county of Nord-Trøndelag were invited to participate in two cross-sectional surveys. Attendance rates were 56% and 42%. The age-adjusted 1-year prevalences, according to the diagnostic criteria of the International Headache Society, sex-ratios and attack frequencies were assessed. The migraine prevalence increased from 12.1% to 13.2% (P < 0.001), but the sex ratio did not change. The prevalence of non-migrainous headache overall decreased (26.0% vs 24.2%; P < 0.001). The prevalences of ‘headache suffering’ (37.4%), chronic daily headache (2.5%) and medication overuse headache (1.0%) remained stable. Apart from a small increase of migraine, headache prevalences remained essentially stable among adults in a Norwegian county during an 11-year period.

Low socioeconomic status is associated with chronic musculoskeletal complaints among 46,901 adults in Norway:

Aims: A study was undertaken to evaluate the relationship between socioeconomic status (SES) and chronic musculoskeletal complaints (MSC), and to determine how this relationship is influenced by change in SES. Methods: Two consecutive public health surveys within the county of Nord-Trøndelag, Norway, were conducted in 1984—86 (HUNT-1) and 1995—97 (HUNT-2). Among 46,901 adults who participated in both surveys, 24,127 persons (51%) in HUNT-2 who reported MSC continuously for at least 3 months during the past year were defined as having chronic MSC. Prevalence of chronic MSC was estimated at nine anatomical sites using multiple logistic regression with odds ratio (OR) and 95% confidence interval (CI) as measures of association with SES. Results: When defining SES by educational level, type of occupation, or income, low status was associated with increased prevalence of chronic MSC (age-adjusted analyses). The negative influence of low education or low occupation level was not eliminated by increasing the level of education or occupation from HUNT-1 to HUNT-2, in contrast with what was found for individuals with higher income level in HUNT-2 than in HUNT-1. The relationship with SES was more evident among individuals with musculoskeletal symptoms≥15 days during the past month than among those with less than 15 days, evident at all nine different anatomical sites. The strongest relationship was found between low SES and prevalence of widespread chronic MSC. Conclusions: Individuals with low SES had higher prevalence of chronic MSC than those with high SES. Future studies should try to clarify whether chronic MSC are a cause or consequence of low SES.

The association between headache and Val158Met polymorphism in the catechol–O–methyltransferase gene: the HUNT Study

The catechol–O–methyltransferase (COMT) gene contains a functional polymorphism, Val158Met, that has been found to influence human pain perception, and one study has found that migraine was less likely among those with the Val/Val polymorphism. In the 1995–97 Nord–Trøndelag Health (HUNT) Study, the association between the Val158Met polymorphism and headache was evaluated in a random sample of 2451 individuals. No association between Val158Met polymorphism and migraine was found. Among women, a lower prevalence of non–migrainous headache was found among individuals with the Val/Val genotype than among those with other genotypes (26.2% vs. 33.6%, p=0.04). That non–migrainous headache was less likely among women with the Val/Val genotype may be an incidental finding, but should be investigated in further studies.