Estimates of familial cancer risk from population-based studies are essential components of cancer risk prediction.
To estimate familial risk and heritability of cancer types in a large twin cohort.
...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.
Shared environmental and heritable risk factors among pairs of twins.
The main outcome was incident cancer. Time-to-event analyses were used to estimate familial risk (risk of cancer in an individual given a twin's 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.
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%).
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.
Summary
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.
The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male ...monozygotic twin pairs discordant for physical activity.
From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses.
According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P < 0.001.
Among healthy adult male twins in their mid-30s, a greater level of physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.
Previous studies with limited follow-up times have suggested that sleep-related traits are associated with an increased risk of incident dementia or cognitive decline. We investigated the association ...between midlife sleep characteristics and late life cognitive function.
A follow-up study with a median follow-up time of 22.5 (range 15.8-25.7) years assessing the association between midlife sleep characteristics and later cognitive function.
Questionnaire data from 1981 were used in the assessment of sleep characteristics, use of hypnotics, and covariates at baseline. Between 1999 and 2007, participants were assigned a linear cognitive score with a maximum score of 51 based on a telephone interview (mean score 38.3, SD 6.1). Linear regression analyses were controlled for age, sex, education, ApoE genotype, and follow-up time.
2,336 members of the Finnish Twin cohort who were at least 65 years of age.
N/A.
Baseline short (< 7 h/day) and long (> 8 h/day) sleepers had lower cognitive scores than participants sleeping 7-8 h/ day (β = -0.84, P = 0.014 and β = -1.66, P < 0.001, respectively). As compared to good sleep quality, poor or rather poor sleep quality was associated with a lower cognitive score (β = -1.00, P = 0.011). Also, the use of hypnotics ≥ 60 days per year was associated with poorer cognitive function (β = -1.92, P = 0.002).
This is the first study indicating that midlife sleep length, sleep quality, and use of hypnotics are associated with late life cognitive function. Further confirmation is needed, but sleep-related characteristics may emerge as new risk factors for cognitive impairment.
After intensive, long-term musical training, the auditory system of a musician is specifically tuned to perceive musical sounds. We wished to find out whether a musician′s auditory system also ...develops increased sensitivity to any sound of everyday life, experiencing them as noise. For this purpose, an online survey, including questionnaires on noise sensitivity, musical background, and listening tests for assessing musical aptitude, was administered to 197 participants in Finland and Italy. Subjective noise sensitivity (assessed with the Weinstein′s Noise Sensitivity Scale) was analyzed for associations with musicianship, musical aptitude, weekly time spent listening to music, and the importance of music in each person′s life (or music importance). Subjects were divided into three groups according to their musical expertise: Nonmusicians (N = 103), amateur musicians (N = 44), and professional musicians (N = 50). The results showed that noise sensitivity did not depend on musical expertise or performance on musicality tests or the amount of active (attentive) listening to music. In contrast, it was associated with daily passive listening to music, so that individuals with higher noise sensitivity spent less time in passive (background) listening to music than those with lower sensitivity to noise. Furthermore, noise-sensitive respondents rated music as less important in their life than did individuals with lower sensitivity to noise. The results demonstrate that the special sensitivity of the auditory system derived from musical training does not lead to increased irritability from unwanted sounds. However, the disposition to tolerate contingent musical backgrounds in everyday life depends on the individual′s noise sensitivity.
We studied whether objectively measured physical activity (PA) and sedentary behavior (SB) are associated with cognition in Finnish elderly twins.
This cross-sectional study comprised twins born in ...Finland from 1940 to 1944 in the Older Finnish Twin Cohort (mean age, 72.9 years; 726 persons). From 2014 to 2016, cognition was assessed with a validated telephonic interview, whereas PA was measured with a waist-worn accelerometer.
In between-family models, SB and light physical activity had significant linear associations with cognition after adjusting for age, sex, wearing time, education level, body mass index, and living condition (SB: β-estimate, −0.21 95% confidence intervals, −0.42 to −0.003; light physical activity: β-estimate, 0.30 95% confidence intervals, 0.02–0.58). In within-family models, there were no significant linear associations between objectively measured PA and cognition.
Objectively measured light physical activity and SB are associated with cognition in Finnish twins in their seventies, but the associations were attributable to genetic and environmental selection.
•Objectively measured physical activity was associated with cognition in elderly.•Light physical activity was associated with better cognition in individuals.•Sedentary behavior was associated with worse cognition in individuals.•Twin analyses show similar genetics and environment contributing to the associations.
Abstract Introduction On the basis of the proxy measures of cognitive reserve, we created a middle age self-report risk score for early prediction of dementia. Methods We used a longitudinal ...population-based study of 2602 individuals with a replication sample (N = 1011). Risk score at a mean age of 47 years was based on questions on educational and occupational attainments. Cognitive status at a mean age of 74 was determined via two validated telephone instruments. Results The prevalence of dementia was 10% after a mean follow-up of 28 years. Risk score was a good predictor of dementia: area under the curve = 0.77 (95% confidence interval, 0.74–0.80). The risk of dementia decreased as a function of risk score from 36% to 0%. The risk score was significantly associated with cognition after a mean follow-up of 39 years in the replication sample. Discussion Self-report risk score predicted cognitive functioning and dementia risk 20–40 years later.
Sensitivity to unwanted sounds is common in general and clinical populations. Noise sensitivity refers to physiological and psychological internal states of an individual that increase the degree of ...reactivity to noise in general. The current study investigated the relationship between the Big Five personality dimensions and noise sensitivity using the 240-item NEO Personality Inventory (NEO-PI) and 35-item The Noise-Sensitivity-Questionnaire (NoiSeQ) scales, respectively. Overall, the Big Five accounted for 33% of the variance in noise sensitivity, with the Introversion-Extroversion dimension explaining the most variability. Furthermore, the Big Five personality dimensions (neuroticism, extroversion, openness, agreeableness, and conscientiousness) had an independent effect on noise sensitivity, which were linear. However, additional analyses indicated that the influence of gender and age must be considered when examining the relationship between personality and noise sensitivity. The findings caution against pooling data across genders, not controlling for age, and using personality dimensions in isolation.
Population structure can provide novel insight into the human past, and recognizing and correcting for such stratification is a practical concern in gene mapping by many association methodologies. We ...investigate these patterns, primarily through principal component (PC) analysis of whole genome SNP polymorphism, in 2099 individuals from populations of Northern European origin (Ireland, United Kingdom, Netherlands, Denmark, Sweden, Finland, Australia, and HapMap European-American). The major trends (PC1 and PC2) demonstrate an ability to detect geographic substructure, even over a small area like the British Isles, and this information can then be applied to finely dissect the ancestry of the European-Australian and European-American samples. They simultaneously point to the importance of considering population stratification in what might be considered a small homogeneous region. There is evidence from F(ST)-based analysis of genic and nongenic SNPs that differential positive selection has operated across these populations despite their short divergence time and relatively similar geographic and environmental range. The pressure appears to have been focused on genes involved in immunity, perhaps reflecting response to infectious disease epidemic. Such an event may explain a striking selective sweep centered on the rs2508049-G allele, close to the HLA-G gene on chromosome 6. Evidence of the sweep extends over a 8-Mb/3.5-cM region. Overall, the results illustrate the power of dense genotype and sample data to explore regional population variation, the events that have crafted it, and their implications in both explaining disease prevalence and mapping these genes by association.
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