Kauko Heikkilä

SNORING AS A RISK FACTOR FOR HYPERTENSION AND ANGINA PECTORIS

The association of snoring with hypertension and ischaemic heart disease (IHD) was tested by postal questionnaire in a population of 3847 men and 3664 women aged 40-69 years. Hypertension associated highly significantly with snoring, the relative risk (RR) of hypertension between habitual snorers and never snorers being 1.94 in men and 3.19 in women. This association was also found when adjusting for body-mass index. A significant association between angina pectoris and habitual snoring was observed in men (RR = 2.22). In women the relative risk was not significant. An association between habitual snoring and angina pectoris in men was also found after adjusting for hypertension and body-mass index (RR = 2.01, p less than 0.01). The relative risks for myocardial infarction and hospital admission for IHD for habitual snorers were non-significant.

Hostility as a risk factor for mortality and ischemic heart disease in men.

&NA; We report the association between hostility and the incidence of ischemic heart disease (IHD) in 3,750 Finnish men aged 40–59. Hostility was assessed from self‐ratings on irritability, ease of anger‐arousal, and argumentativeness, and four groups were formed from the summed hostility ratings. At baseline, the age‐adjusted relative risk (RR) of the prevalence of angina pectoris between the highest and lowest hostility groups was 2.88 (95% confidence limits (CL), range 1.71–4.77). A three‐year follow‐up yielded 65 deaths and 109 IHD‐incident cases. Hostility did not predict IHD among healthy men, but among men with previous IHD and hypertension (N = 104), the age‐adjusted RR of IHD between the highest and lowest hostility groups was 12.9 (95% CL, 3.92–42.6). After standardization for smoking, obesity, heavy alcohol use, and snoring, the RR was 14.6 (95% CL, 1.94–110). When the degree of dyspnea at baseline was also standardized, the RR was 21.1 (95% CL, 1.59–282). Our data suggest that extreme hostility is not a consequence of symptom severity; rather, hostility is a strong determinant of coronary attack among hypertensive men with IHD.

Risk of cancer in Finnish children living close to power lines.

OBJECTIVE--To investigate the risk of cancer in children living close to overhead power lines with magnetic fields of > or = 0.01 microteslas (microT). DESIGN--Cohort study. SETTING--The whole of Finland. SUBJECTS--68,300 boys and 66,500 girls aged 0-19 years living during 1970-89 within 500 m of overhead power lines of 110-400 kV in magnetic fields calculated to be > or = 0.01 microT. Subjects were identified by record linkages of nationwide registers. MAIN OUTCOME MEASURES--Numbers of observed cases in follow up for cancer and standardised incidence ratios for all cancers and particularly for nervous system tumours, leukaemia, and lymphoma. RESULTS--In the whole cohort 140 cases of cancer were observed (145 expected; standardised incidence ratio 0.97, 95% confidence interval 0.81 to 1.1). No statistically significant increases in all cancers and in leukaemia and lymphoma were found in children at any exposure level. A statistically significant excess of nervous system tumours was found in boys (but not in girls) who were exposed to magnetic fields of > or = 0.20 microT or cumulative exposure of > or = 0.40 microT years. CONCLUSIONS--Residentia magnetic fields of transmission power lines do not constitute a major public health problem regarding childhood cancer. The small numbers do not allow further conclusions about the risk of cancer in stronger magnetic fields.

Genome-wide meta-analysis identifies new susceptibility loci for migraine

Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P < 5 × 10−8). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

Daytime sleepiness in an adult, Finnish population

Hublin C, Kaprio J, Partinen M, Heikkilä K, Koskenvuo M (Departments of Psychiatry and Neurology and the Department of Public Health (The Finnish Twin Cohort), University of Helsinki, Helsinki; and the Department of Public Health, University of Turku, Turku; Finland). Daytime sleepiness in an adult, Finnish population. J Intern Med 1996; 239: 417–23.

Migraine and Concomitant Symptoms Among 8167 Adult Twin Pairs

We studied the inheritance of migraine and concomitant symptoms among 2690 monozygotic (1524 female and 1166 male) pairs and 5497 dizygotic (2951 female and 2546 male) twin pairs. Our material consists of a population‐based questionnaire study among Finnish twins in 1981. The definition of migraine is based on a questionnaire method.

Heritability of diurnal type: a nationwide study of 8753 adult twin pairs

Twin studies suggest a genetic component in diurnal types. In 1981, a questionnaire sent to the Older Finnish Twin Cohort yielded responses from 2836 adult monozygotic (MZ) and 5917 like‐sexed dizygotic (DZ) twin pairs with four category self‐report on diurnal type. We used structural equation modelling to estimate genetic and environmental components of variance in morningness and eveningness. The model fitting was best when the morningness and the eveningness were analysed together. The ADE‐model (including additive genetic, dominant genetic and non‐shared environmental effects) fitted best to the data. ADE‐models for men and women separately did not differ in a statistically significant manner from the combined model, and similarly ADE‐models for young and old age groups separately did not differ either. The estimate for overall genetic effect (broad sense heritability) was 49.7% (95% confidence interval 46.4–52.8), with the remainder accounted for by environmental factors not shared by siblings. The variance component estimates for the underlying liability to diurnal type were 11.7% (95% CI 0–23.7) for additive genetic factors, 38.0% (24.7–51.3) for genetic factors due to dominance. Genetic effects thus account for about one‐half of the interindividual variability in diurnal type in adults.

Familial Risk and Heritability of Cancer Among Twins in Nordic Countries

IMPORTANCE Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction. OBJECTIVE To estimate familial risk and heritability of cancer types in a large twin cohort. DESIGN, SETTING, AND PARTICIPANTS Prospective study of 80,309 monozygotic and 123,382 same-sex dizygotic twin individuals (N = 203,691) within the population-based registers of Denmark, Finland, Norway, and Sweden. Twins were followed up a median of 32 years between 1943 and 2010. There were 50,990 individuals who died of any cause, and 3804 who emigrated and were lost to follow-up. EXPOSURES Shared environmental and heritable risk factors among pairs of twins. MAIN OUTCOMES AND MEASURES The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twins development of cancer) and heritability (proportion of variance in cancer risk due to interindividual genetic differences) with follow-up via cancer registries. Statistical models adjusted for age and follow-up time, and accounted for censoring and competing risk of death. RESULTS A total of 27,156 incident cancers were diagnosed in 23,980 individuals, translating to a cumulative incidence of 32%. Cancer was diagnosed in both twins among 1383 monozygotic (2766 individuals) and 1933 dizygotic (2866 individuals) pairs. Of these, 38% of monozygotic and 26% of dizygotic pairs were diagnosed with the same cancer type. There was an excess cancer risk in twins whose co-twin was diagnosed with cancer, with estimated cumulative risks that were an absolute 5% (95% CI, 4%-6%) higher in dizygotic (37%; 95% CI, 36%-38%) and an absolute 14% (95% CI, 12%-16%) higher in monozygotic twins (46%; 95% CI, 44%-48%) whose twin also developed cancer compared with the cumulative risk in the overall cohort (32%). For most cancer types, there were significant familial risks and the cumulative risks were higher in monozygotic than dizygotic twins. Heritability of cancer overall was 33% (95% CI, 30%-37%). Significant heritability was observed for the cancer types of skin melanoma (58%; 95% CI, 43%-73%), prostate (57%; 95% CI, 51%-63%), nonmelanoma skin (43%; 95% CI, 26%-59%), ovary (39%; 95% CI, 23%-55%), kidney (38%; 95% CI, 21%-55%), breast (31%; 95% CI, 11%-51%), and corpus uteri (27%; 95% CI, 11%-43%). CONCLUSIONS AND RELEVANCE In this long-term follow-up study among Nordic twins, there was significant excess familial risk for cancer overall and for specific types of cancer, including prostate, melanoma, breast, ovary, and uterus. This information about hereditary risks of cancers may be helpful in patient education and cancer risk counseling.

Genetic Linkage to Chromosome 22q12 for a Heavy-Smoking Quantitative Trait in Two Independent Samples

We conducted a genomewide linkage screen of a simple heavy-smoking quantitative trait, the maximum number of cigarettes smoked in a 24-h period, using two independent samples: 289 Australian and 155 Finnish nuclear multiplex families, all of which were of European ancestry and were targeted for DNA analysis by use of probands with a heavy-smoking phenotype. We analyzed the trait, using a regression of identity-by-descent allele sharing on the sum and difference of the trait values for relative pairs. Suggestive linkage was detected on chromosome 22 at 27-29 cM in each sample, with a LOD score of 5.98 at 26.96 cM in the combined sample. After additional markers were used to localize the signal, the LOD score was 5.21 at 25.46 cM. To assess the statistical significance of the LOD score in the combined sample, 1,000 simulated genomewide screens were conducted, resulting in an empirical P value of .006 for the LOD score of 5.21. This linkage signal is driven mainly by the microsatellite marker D22S315 (22.59 cM), which had a single-point LOD score of 5.41 in the combined sample and an empirical P value <.001 from 1,000 simulated genomewide screens. This marker is located within an intron of the gene ADRBK2, encoding the beta-adrenergic receptor kinase 2. Fine mapping of this linkage region may reveal variants contributing to heaviness of smoking, which will lead to a better understanding of the genetic mechanisms underlying nicotine dependence.

Interpersonal conflict as a predictor of work disability: A follow-up study of 15,348 finnish employees

This 6-year follow-up study investigates the impact of interpersonal conflict at work on work disability among 8,021 male and 7,327 female employees aged 24 to 65 years at baseline. Marital status, marital conflict, monotonous work, hectic work pace, hostility, neuroticism, life dissatisfaction, and experienced stress of daily activities were included in survival analyses, which were adjusted for age, social status, and general health status. Interpersonal conflict at work predicted work disability only among women (RR 1.56, CL 1.01-2.39). This risk was confined to women who reported simultaneous marital conflicts (RR 2.54, CL 1.03-6.22). When included in further analyses, life dissatisfaction was a significant risk factor among both genders, but monotonous work, neuroticism, and experienced stress of daily activities were risk factors only among men. These data suggest that interpersonal conflict could be a determinant of work disability, and this indicates the importance of gender and marital factors.