ABSTRACT
Usual sleep duration is a heritable trait correlated with psychiatric morbidity, cardiometabolic disease and mortality, although little is known about the genetic variants influencing this trait. A genome-wide association study (GWAS) of usual sleep duration was conducted using 18 population-based cohorts totaling 47 180 individuals of European ancestry. Genome-wide significant association was identified at two loci. The strongest is located on chromosome 2, in an intergenic region 35- to 80-kb upstream from the thyroid-specific transcription factor PAX8 (lowest P=1.1 × 10(-9)). This finding was replicated in an African-American sample of 4771 individuals (lowest P=9.3 × 10(-4)). The strongest combined association was at rs1823125 (P=1.5 × 10(-10), minor allele frequency 0.26 in the discovery sample, 0.12 in the replication sample), with each copy of the minor allele associated with a sleep duration 3.1 min longer per night. The alleles associated with longer sleep duration were associated in previous GWAS with a more favorable metabolic profile and a lower risk of attention deficit hyperactivity disorder. Understanding the mechanisms underlying these associations may help elucidate biological mechanisms influencing sleep duration and its association with psychiatric, metabolic and cardiovascular disease.
Subject(s)
Dyssomnias/genetics , Sleep/genetics , Adult , Black or African American/genetics , Aged , Female , Genetic Association Studies , Genome-Wide Association Study , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Self Report , White People/geneticsABSTRACT
BACKGROUND: Differences in lower esophageal sphincter (LES) and peristaltic function and in transient LES relaxations (TLESR) have been described in patients with gastro-esophageal reflux disease (GERD). However, some of these differences may be the result of chronic GERD rather than being an underlying contributory factor. METHODS: Twins discordant for GERD symptoms, i.e., only one twin had GERD symptoms, underwent standard LES and esophageal body manometry, and then using a sleeve sensor prolonged LES and pH monitoring, 30 min before and 60 min after a 250 mL 1200 kcal lipid meal. KEY RESULTS: Eight monozygotic and 24 dizygotic female twins were studied. Although there was no difference in preprandial LES pressure (symptomatic 13.2 ± 7.1 mmHg vs asymptomatic 15.1 ± 6.2 mmHg, P = 0.4), LES pressure fell further postprandially in symptomatic twins (LES pressure area under the curve 465 ± 126 vs 331 ± 141 mmHg h, P < 0.01). 12/37 (32%) of acid reflux episodes in symptomatic twins occurred due to low LES pressure or deep inspiration/strain and 0/17 in asymptomatic twins (P = 0.01). There was no difference between symptomatic and asymptomatic twins in: peristaltic amplitude, ineffective esophageal body motility, hiatus hernia prevalence, or LES length. There was also no difference in TLESR frequency preprandially (symptomatic median 1(range 0-2) vs asymptomatic 0(0-2), P = 0.08) or postprandially (2.5(1-8) vs 3(1-6), P = 0.81). CONCLUSIONS & INFERENCES: Twins with GERD symptoms had lower postprandial LES pressure and given the close genetic link between the twins, it is possible that such differences are caused by GERD. Acid reflux episodes associated with a hypotensive LES were seen in symptomatic, but not in asymptomatic twins.
Subject(s)
Diseases in Twins/genetics , Diseases in Twins/physiopathology , Gastroesophageal Reflux/genetics , Gastroesophageal Reflux/physiopathology , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Adult , Aged , Diseases in Twins/diagnosis , Female , Gastroesophageal Reflux/diagnosis , Humans , Male , Middle Aged , Surveys and QuestionnairesABSTRACT
To further investigate brain structure and function in 26 handedness discordant monozygotic twin pairs (MzHd), MRI and behavioural assessments were carried out. These showed significant correlation between language-specific functional laterality in inferior and middle frontal gyri, and anterior corpus callosum. Previous studies of handedness discordant monozygotic twins failed to resolve the issue concerning handedness and hemispheric laterality for language due to methodological disparities. The results would be relevant to genetic theories as well as to brain structure:function explanations. MzHd twins underwent MRI and fMRI scanning as well as behavioural assessment of motor performance and cognition. There were significant differences on MRI and fMRI laterality measures, as well as a significant correlation between anterior callosal widths and functional laterality. LH twins showed higher frequencies of atypical functional laterality. There was no significant within-twin pair correlation on fMRI verbal laterality, nor did results show within-twin pair differences on verbal fluency or IQ. Implications for the field of laterality research pertain to frontal hemispheric equipotentiality for verbal processes in healthy individuals. In particular, there can be an apparent lack of cognitive 'cost' to atypical laterality. An fMRI verbal laterality index correlated significantly with corpus callosum widths near Broca's area.
Subject(s)
Brain Mapping/methods , Corpus Callosum/physiology , Functional Laterality , Magnetic Resonance Imaging , Twins, Monozygotic , Adult , Aged , Birth Order , Chi-Square Distribution , Cognition , Female , Functional Laterality/genetics , Humans , Intelligence , Intelligence Tests , Middle Aged , Motor Activity , Neuropsychological Tests , Phenotype , Regression Analysis , Twins, Monozygotic/genetics , Verbal BehaviorABSTRACT
BACKGROUND: Dysmorphic concern refers to an excessive preoccupation with a perceived or slight defect in physical appearance. It lies on a continuum of severity from no or minimal concerns to severe concerns over one's appearance. The present study examined the heritability of dysmorphic concerns in a large sample of twins. METHOD: Twins from the St Thomas UK twin registry completed a valid and reliable self-report measure of dysmorphic concerns, which also includes questions about perceived body odour and malfunction. Twin modelling methods (female twins only, n=3544) were employed to decompose the variance in the liability to dysmorphic concerns into additive genetic, shared and non-shared environmental factors. RESULTS: Model-fitting analyses showed that genetic factors accounted for approximately 44% [95% confidence intervals (CI) 36-50%] of the variance in dysmorphic concerns, with non-shared environmental factors and measurement error accounting for the remaining variance (56%; 95% CI 50-63%). Shared environmental factors were negligible. The results remained unchanged when excluding individuals reporting an objective medical condition/injury accounting for their concern in physical appearance. CONCLUSIONS: Over-concern with a perceived or slight defect in physical appearance is a heritable trait, with non-shared environmental factors also playing an important role in its causation. The results are relevant for various psychiatric disorders characterized by excessive concerns in body appearance, odour or function, including but not limited to body dysmorphic disorder.
Subject(s)
Body Dysmorphic Disorders/genetics , Gene-Environment Interaction , Adult , Aged , Female , Genetic Predisposition to Disease , Humans , Male , Middle Aged , Twins, Dizygotic/psychology , Twins, Monozygotic/psychologyABSTRACT
BACKGROUND: Age-related cognitive decline begins in mid-life and continues with advancing age. Leukocyte telomere length (LTL) shortens with age, and inflammation and oxidative stress enhance this process. Shorter LTL is associated with dementia. METHODS: The relationship between cognitive function and LTL was investigated in a cross-sectional study of 382 women (mean age 50.6 years, range 19-78), not diagnosed with any form of dementia or cognitive impairment, from the TwinsUK cohort using six tests from the Cambridge neuropsychological test automated battery (CANTAB). RESULTS: After adjusting for age and estimated prior intellectual ability, we observed significant correlations of LTL with episodic memory and associated learning (PAL, p=0.032), recognition memory for non-verbal patterns (DMS, p=0.007), and working memory capacity (SSP, p=0.003). In pairs of twins discordant for LTL the twin with longer telomeres also had significantly better DMS (p<0.05) and SSP (p<0.013) scores than their co-twin with shorter telomeres. The correlations between these two scores and LTL was significant both in women over the median mean age and in those below the median age, and remained significant after statistical adjustment for potential confounders. CONCLUSIONS: Leukocyte telomere length correlates with a subset of measures of cognitive performance, suggesting that it might be a biomarker of cognitive aging in women before the onset of dementia.
Subject(s)
Cognition/physiology , Leukocytes/physiology , Statistics as Topic , Telomere/physiology , Adolescent , Adult , Age Factors , Aged , Association Learning/physiology , Cohort Studies , Cross-Sectional Studies , Female , Humans , Memory/physiology , Middle Aged , Neuropsychological Tests , Space Perception/physiology , Young AdultABSTRACT
Migraine headache (with and without aura) is common in the general population and is known to be influenced by genetic factors with heritability estimates between 34-57%. Antiphospholipid syndrome (APS) is a hypercoagulable state characterized by clinical features including venous and arterial thromboses, pregnancy loss and migraine, and by association with antiphospholipid antibodies (aPL). Numerous small studies have investigated whether aPL are associated with migraine in the general population--with contradictory results. In this study, the question was addressed by studying the prevalence of aPL in members of monozygotic (MZ) twin pairs differing in their migraine status. Such twins provide a unique natural experiment, matched as they are for age, sex and genetic factors, and allow the role of environmental factors, such as aPL, to be determined. Despite 95% power to detect a difference of 0.59 IgG units per litre in anticardiolipin antibody IgG titres, no difference in prevalence of aPL could be detected in migraine-discordant MZ twins.
Subject(s)
Antibodies, Anticardiolipin/blood , Migraine Disorders , Twins, Monozygotic , Adult , Aged , Aged, 80 and over , Female , Humans , Immunoglobulin G/blood , Immunoglobulin M/blood , Lipoproteins, LDL/immunology , Male , Middle Aged , Migraine Disorders/epidemiology , Migraine Disorders/genetics , Migraine Disorders/immunology , Prevalence , Seroepidemiologic Studies , beta 2-Glycoprotein I/immunologyABSTRACT
BACKGROUND: Surveys have shown opposition to human reproductive cloning (HRC) in many countries. Views of identical (monozygotic, MZ) twins are of particular interest, as they naturally share 100% of their genes. We investigated attitudes of British twins towards HRC in the context of assisted reproduction technologies (ART) and gene selection. METHODS: About 4651 identical and non-identical (dizygotic, DZ) twins expressed their degree of agreement or disagreement to nine statements relating to ART, gene selection and HRC in a self-completion questionnaire. RESULTS: Most subjects (70% and 78% respectively) did not regard the use of medical technologies to treat infertility as interfering with either nature or God's will, despite believing that infertility is not a disease (54%). Attitudes to gene selection and HRC were context dependent, with more favourable views towards preventing serious diseases than towards enhancing traits. About 44% supported a permanent ban of HRC. MZ twins were significantly more likely to agree that HRC should be allowed for medical purposes, such as saving a sibling's life, than were DZ twins. Increasing religiosity generally correlated with more negative attitudes. CONCLUSIONS: Many attitudes are context dependent. More positive views of MZ twins towards HRC could be linked to their experience with being genetically identical.
Subject(s)
Attitude to Health , Cloning, Organism/psychology , Genetics, Medical , Reproductive Techniques, Assisted/psychology , Twins, Dizygotic/psychology , Twins, Monozygotic/psychology , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Nuclear Transfer Techniques/psychologySubject(s)
Cold Temperature , Raynaud Disease/epidemiology , Raynaud Disease/genetics , Twins , Vasoconstriction/genetics , Adult , Body Temperature , Diseases in Twins , Female , Humans , Immersion , Incidence , Middle Aged , Raynaud Disease/physiopathology , Severity of Illness Index , Surveys and Questionnaires , Twins, MonozygoticABSTRACT
OBJECTIVE: Although medications to prevent osteoporotic fractures have been proven to be effective, compliance to these therapies is generally poor. Therapeutic regimens for different anti-osteoporotic medications differ widely and it is currently unknown which regimen would be most preferred by patients. RESEARCH DESIGN AND METHODS: We conducted a large, population-based study to discern which therapeutic attributes would be most preferable to a population representative of the age and sex distribution of patients with osteoporosis. RESULTS: Our study sample was restricted to persons aged 55 years and over and comprised 2485 individuals (mean age of 64.5 years). The study population was predominantly female (90.3%) and two-thirds of the respondents reported current daily medication use. Nearly half (45%) of the study population preferred to take medications daily, while one in five preferred weekly therapy and 30% preferred monthly therapy (p < 0.0001 for between proportion comparisons). When given the option of choosing between three different medication regimen scenarios, those subjects not currently using anti-osteoporotic medications preferred a theoretical regimen which was daily and did not involve subsequent fasting and maintaining an upright posture. CONCLUSIONS: Our data suggest that compliance with osteoporotic medications could be improved if patients are able to choose a therapeutic regimen best suited to their particular needs. The majority of subjects preferred a drug which was taken daily and with minimal inconvenience, rather than a weekly drug with slightly more inconvenience. Given that most physicians currently prescribe anti-osteoporotic therapy as a weekly regimen, at the time of diagnosis physicians should ascertain which regimen would be most preferable to patients prior to initiating therapy.
Subject(s)
Osteoporosis/prevention & control , Patient Compliance , Patient Satisfaction/statistics & numerical data , Aged , Cohort Studies , Diphosphonates/administration & dosage , Diphosphonates/adverse effects , Diphosphonates/therapeutic use , Drug Administration Schedule , Fasting , Female , Humans , Male , Middle Aged , Organometallic Compounds/administration & dosage , Organometallic Compounds/adverse effects , Organometallic Compounds/therapeutic use , Osteoporosis/psychology , Patient Compliance/psychology , Posture , Raloxifene Hydrochloride/administration & dosage , Raloxifene Hydrochloride/adverse effects , Raloxifene Hydrochloride/therapeutic use , Registries , Single-Blind Method , Surveys and Questionnaires , Teriparatide/administration & dosage , Teriparatide/adverse effects , Teriparatide/therapeutic use , Thiophenes/administration & dosage , Thiophenes/adverse effects , Thiophenes/therapeutic use , Twins/psychologyABSTRACT
BACKGROUND: Premature ovarian failure (POF) before 40 years of age from natural causes affects approximately 1% of adult women, with minor variations between ethnic groups. A recent case of ovarian transplantation between young monozygotic (MZ) twins in which one had undergone unexplained POF at 14 years has prompted a study of the prevalence of POF. METHODS: Menopausal ages of 832 Australian and UK female twin-pairs were extracted from volunteer national twin registry databases containing medical, reproductive and lifestyle data surveyed by mail questionnaire. Surgical menopause was an exclusion criterion. RESULTS: The prevalence of POF in both MZ and dizygotic (DZ) twins was similar in both registries and 3- to 5-fold greater than the general population at age thresholds 40 and 45 years. No specific factors were found to account for the higher risk of early menopause. Some twins of both zygosities were highly discordant for menopausal age (>or=10 years). Nevertheless, there was significant intra-twin dependence, especially for MZ twins, and the average age difference at last menses was greater in DZ twin-pairs. CONCLUSION: Both MZ and DZ twins are at higher risk of POF. Despite some striking differences within MZ twin-pairs, menopausal ages were more concordant than for DZ twin-pairs, confirming that the timing of menopause has a heritable component.
Subject(s)
Diseases in Twins/epidemiology , Primary Ovarian Insufficiency/epidemiology , Twins, Dizygotic , Twins, Monozygotic , Adult , Australia/epidemiology , Female , Humans , Menopause , Middle Aged , Prevalence , United Kingdom/epidemiologyABSTRACT
Low socio-economic status (SES) is associated with a shortened life expectancy, but its effect on aging is unknown. The rate of white-blood-cell (WBC) telomere attrition may be a biological indicator of human aging. We tested the hypothesis that SES is associated with telomere attrition independent of known risk factors influencing the aging process. We studied 1552 female twins. A venous blood sample was taken from each twin and isolated WBCs used for extraction of DNA. Terminal restriction fragment length (TRFL) was measured. Questionnaire data were collected on occupation, education, income, smoking, exercise, height and weight. Standard multiple linear regression and multivariate analyses of variance tested for associations between SES and TRFL, adjusting for covariates. A discordant twin analysis was conducted on a subset to verify findings. WBC telomere length was highly variable but significantly shorter in lower SES groups. The mean difference in TRFL between nonmanual and manual SES groups was 163.2 base pairs (bp) of which 22.9 bp (approximately 14%) was accounted for by body mass index, smoking and exercise. Comparison of TRFL in the 17 most discordant SES twin pairs confirmed this difference. Low SES, in addition to the harmful effects of smoking, obesity and lack of exercise, appears to have an impact on telomere length.
Subject(s)
Aging , Leukocytes , Socioeconomic Factors , Telomere , Adolescent , Adult , Aged , Cohort Studies , Female , Humans , Linear Models , Middle Aged , Multivariate Analysis , Polymorphism, Restriction Fragment Length , Registries , Risk Factors , Surveys and Questionnaires , Twins, Dizygotic , Twins, Monozygotic , White PeopleABSTRACT
Obesity and smoking are important risk factors for many age-related diseases. Both are states of heightened oxidative stress, which increases the rate of telomere erosion per replication, and inflammation, which enhances white blood cell turnover. Together, these processes might accelerate telomere erosion with age. We therefore tested the hypothesis that increased body mass and smoking are associated with shortened telomere length in white blood cells. We investigated 1122 white women aged 18-76 years and found that telomere length decreased steadily with age at a mean rate of 27 bp per year. Telomeres of obese women were 240 bp shorter than those of lean women (p=0.026). A dose-dependent relation with smoking was recorded (p=0.017), and each pack-year smoked was equivalent to an additional 5 bp of telomere length lost (18%) compared with the rate in the overall cohort. Our results emphasise the pro-ageing effects of obesity and cigarette smoking.
Subject(s)
Obesity/genetics , Smoking/genetics , Telomere/pathology , Adolescent , Adult , Aged , Aging/genetics , Female , Humans , Middle Aged , Risk FactorsABSTRACT
BACKGROUND: Osteoporosis is associated with morbidity and mortality, particularly in postmenopausal women. The effect of moderate alcohol intake on bone mineral density (BMD) and fracture risk remains unclear. OBJECTIVE: To carry out a twin study to investigate this effect while controlling for genetic effects and other confounding variables. METHODS: BMD was determined at the hip and lumbar spine in 46 pairs of monozygotic twins discordant for alcohol consumption. Biochemical evidence of altered bone metabolism was sought. RESULTS: A positive association between alcohol consumption and BMD was shown, in contrast to the negative effect of smoking on BMD. Markers of bone turnover were not associated with alcohol or BMD. CONCLUSIONS: Moderate alcohol consumption is not harmful to bone health in women and may even be beneficial. Beneficial effects do not appear to be mediated through an action on bone metabolism.
Subject(s)
Alcohol Drinking/physiopathology , Bone Density/drug effects , Ethanol/pharmacology , Female , Hip Joint/physiology , Humans , Lumbar Vertebrae/physiology , Twins, Monozygotic/physiologyABSTRACT
BACKGROUND: A number of families have been described which include multiple members with symptomatic, endoscopic, or complicated gastro-oesophageal reflux disease (GORD). First degree relatives of patients with GORD are more likely to suffer with GORD symptoms. These observations raise the possibility of a genetic contribution to the aetiology of GORD. AIMS: To determine the relative contribution of genetic factors to GORD by evaluating GORD symptoms in monozygotic (MZ) and dizygotic (DZ) twins. METHODS: A total of 4480 unselected twin pairs, identified from a national volunteer twin register, were asked to complete a validated symptom questionnaire. GORD was defined as symptoms of heartburn or acid regurgitation at least weekly during the past year. RESULTS: Replies were obtained from 5032 subjects (56% response rate). A total of 1960 twin pairs were evaluable: 928 MZ pairs (86 male pairs, mean (SD) age 52 (13) (range 19-81) years) and 1032 DZ pairs (71 male pairs, mean age 52 (13) (20-82) years). The prevalence of GORD among both groups of twins was 18%. Casewise concordance rates were significantly higher for MZ than DZ twins (42% v 26%; p<0.001). Multifactorial liability threshold modelling suggests that additive genetic effects combined with unique environmental factors provide the best model for GORD. Heritability estimates suggest that 43% (95% confidence interval 32-55%) of the variance in liability to GORD is due to additive genetic factors. CONCLUSIONS: There is a substantial genetic contribution to the aetiology of GORD.
Subject(s)
Gastroesophageal Reflux/genetics , Adult , Aged , Aged, 80 and over , Female , Humans , Logistic Models , Male , Middle Aged , Phenotype , Regression AnalysisABSTRACT
OBJECTIVES: To estimate the heritability of frozen shoulder (FS) and tennis elbow (TE) and to examine the two disorders for possible genetic or environmental associations. METHODS: Self-reporting questionnaire data on risk factors for, and a physician diagnosis of, FS or TE were obtained from 865 monozygotic (MZ) and 963 dizygotic (DZ) unselected female twin pairs aged between 20 and 76 yr registered with the St Thomas' UK Adult Twin Registry. The heritability of each disorder was estimated in a classic twin study. The association between FS and TE was then explored by log-linear modelling comparing MZ with DZ individuals and twin pairs for the presence of both disorders. RESULTS: The prevalence of FS and TE were 11.6 and 16.7%, respectively. A heritability of 42% was estimated for FS and 40% for TE after adjusting for age. There was no confounding by environmental risk factors. Log-linear modelling demonstrated FS and TE, independently, to be associated within members of a twin pair and confirmed a stronger association in MZ than DZ pairs. In addition the two disorders occurred together 2-3 times more frequently in individuals than would be expected by chance. However, there was no association between FS and TE across members of a twin pair, implying no evidence for a shared genetic component to the two disorders. CONCLUSIONS: Genetic factors are implicated in the aetiology of both frozen shoulder and tennis elbow but are independent of each other. The two disorders occur together 2-3 times more frequently than by chance in individuals. However, the association is most likely mediated by individual-specific environmental factors common to the two conditions and not by a common genetic susceptibility.
Subject(s)
Bursitis/genetics , Diseases in Twins/genetics , Genetic Predisposition to Disease , Shoulder Joint , Tennis Elbow/genetics , Adult , Aged , Female , Humans , Middle Aged , Odds Ratio , Registries , Risk Factors , Twins, Dizygotic , Twins, MonozygoticABSTRACT
OBJECTIVES: To compare the performance of a portable radiometer with thermal imaging and to assess the potential for radiometry to provide a practical alternative for assessing vascular responsiveness in Raynaud's phenomenon (RP). METHODS: Subjects comprised 18 patients with diagnosed RP and 19 non-RP subjects. A thermal imager (Starsight) and a portable radiometer (Cyclops) measured digital temperature at baseline and the subsequent drop and rise in temperature following a cold challenge test. RESULTS: The intra-class correlations between the two instruments for all three measures exceeded 80%. The overall performance of each instrument was almost the same, the Starsight thermal imager correctly classifying 84% of subjects as RP or non-RP and the Cyclops portable radiometer correctly classifying 86% of subjects. The sensitivity of the thermal imager was 83%, compared with 89% for the portable radiometer; the specificity of both instruments was 84%. The positive and negative predictive values of the thermal imager were 83 and 84% respectively, and those for the portable radiometer were 84 and 89%. CONCLUSIONS: The two instruments performed equally well and the differences between them in their absolute measurements did not influence their ability to detect RP. Portable radiometry provides a practical, cheap, accurate and reliable alternative to thermal imaging and has the potential to be used in range of clinical and epidemiological settings.
Subject(s)
Radiometry/instrumentation , Raynaud Disease/diagnosis , Adolescent , Adult , Cold Temperature , Female , Humans , Middle Aged , Regional Blood Flow , ThermographyABSTRACT
The objective of this study was to estimate how much of an individual's appreciation of humour is influenced by genetic factors, the shared environment or the individual's unique environment. A population-based classical twin study of 127 pairs of female twins (71 monozygous (MZ) and 56 dizygous (DZ) pairs) aged 20-75 from the St Thomas' UK Adult Twin Registry elicited responses to five 'Far Side' Larson cartoons on a scale of 0-10. Within both MZ and DZ twin pairs, the tetrachoric correlations of responses to all five cartoons were significantly greater than zero. Furthermore, the correlations for MZ and DZ twins were of similar magnitude and in some cases the DZ correlation was greater than that of the MZ twins. This pattern of correlations suggests that shared environment rather then genetic effects contributes to cartoon appreciation. Multivariate model-fitting confirmed that these data were best explained by a model that allowed for the contribution of the shared environment and random environmental factors, but not genetic effects. However, there did not appear to be a general humour factor underlying responses to all five cartoons and no effect of age was seen. The shared environment, rather than genetic factors, explains the familial aggregation of humour appreciation as assessed by the specific 'off the wall' cognitive type of cartoons used in this study.