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For over 100 years, the genetics of human anthropometric traits has attracted scientific interest. In particular, height and body mass index (BMI, calculated as kg/m2) have been under intensive genetic research. However, it is still largely unknown whether and how heritability estimates vary between human populations. Opportunities to address this question have increased recently because of the establishment of many new twin cohorts and the increasing accumulation of data in established twin cohorts. We started a new research project to analyze systematically (1) the variation of heritability estimates of height, BMI and their trajectories over the life course between birth cohorts, ethnicities and countries, and (2) to study the effects of birth-related factors, education and smoking on these anthropometric traits and whether these effects vary between twin cohorts. We identified 67 twin projects, including both monozygotic (MZ) and dizygotic (DZ) twins, using various sources. We asked for individual level data on height and weight including repeated measurements, birth related traits, background variables, education and smoking. By the end of 2014, 48 projects participated. Together, we have 893,458 height and weight measures (52% females) from 434,723 twin individuals, including 201,192 complete twin pairs (40% monozygotic, 40% same-sex dizygotic and 20% opposite-sex dizygotic) representing 22 countries. This project demonstrates that large-scale international twin studies are feasible and can promote the use of existing data for novel research purposes.

The International Network of Twin Registries (INTR) aims to foster scientific collaboration and promote twin research on a global scale by working to expand the resources of twin registries around the world and make them available to researchers who adhere to established guidelines for international collaboration. Our vision is to create an unprecedented scientific network of twin registries that will advance knowledge in ways that are impossible for individual registries, and includes the harmonization of data. INTR will also promote a broad range of activities, including the development of a website, formulation of data harmonization protocols, creation of a library of software tools for twin studies, design of a search engine to identify research partners, establishment of searchable inventories of data and biospecimens, development of templates for informed consent and data sharing, organization of symposia at International Society of Twin Studies conferences, support for scholar exchanges, and writing grant proposals.

Background: Informal caregiving can be deleterious to mental health, but research results are inconsistent and may reflect an interaction between caregiving and vulnerability to stress., Methods: We examined psychological distress among 1,228 female caregiving and non-caregiving twins. By examining monozygotic and dizygotic twin pairs discordant for caregiving, we assessed the extent to which distress is directly related to caregiving or confounded by common genes and environmental exposures., Results: Caregiving was associated with distress as measured by mental health functioning, anxiety, perceived stress, and depression. The overall association between caregiving and distress was confounded by common genes and environment for mental health functioning, anxiety, and depression. Common environment also confounded the association of caregiving and perceived stress., Conclusions: Vulnerability to distress is a factor in predicting caregivers' psychosocial functioning. Additional research is needed to explicate the mechanisms by which common genes and environment increase the risk of distress among informal caregivers.

Background: There is a dearth of knowledge about the link between cortisol and pain sensitivity., Purpose: We examined the association of salivary cortisol with indices of cold pain sensitivity in 198 female twins and explored the role of familial confounding., Methods: Three-day saliva samples were collected for cortisol levels and a cold pressor test was used to collect pain ratings and time to threshold and tolerance. Linear regression modeling with generalized estimating equations examined the overall and within-pair associations., Results: Lower diurnal variation of cortisol was associated with higher pain ratings at threshold (p = 0.02) and tolerance (p < 0.01). The relationship of diurnal variation with pain ratings at threshold and tolerance was minimally influenced by familial factors (i.e., genetics and common environment)., Conclusions: Understanding the genetic and non-genetic mechanisms underlying the link between HPA axis dysregulation and pain sensitivity may help to prevent chronic pain development and maintenance.

Diurnal preference changes across the lifespan. However, the mechanisms underlying this age-related shift are poorly understood. The aim of this twin study was to determine the extent to which genetic and environmental influences on diurnal preference are moderated by age. Seven hundred and sixty-eight monozygotic and 674 dizygotic adult twin pairs participating in the University of Washington Twin Registry completed the reduced Morningness-Eveningness Questionnaire as a measure of diurnal preference. Participants ranged in age from 19 to 93 years (mean = 36.23, SD = 15.54) and were categorized on the basis of age into three groups: younger adulthood (19-35 years, n = 1715 individuals), middle adulthood (36-64 years, n = 1003 individuals) and older adulthood (65+ years, n = 168 individuals). Increasing age was associated with an increasing tendency towards morningness (r = 0.42, p < 0.001). Structural equation modeling techniques parsed the variance in diurnal preference into genetic and environmental influences for the total sample as well as for each age group separately. Additive genetic influences accounted for 52%[46-57%], and non-shared environmental influences 48%[43-54%], of the total variance in diurnal preference. In comparing univariate genetic models between age groups, the best-fitting model was one in which the parameter estimates for younger adults and older adults were equated, in comparison with middle adulthood. For younger and older adulthood, additive genetic influences accounted for 44%[31-49%] and non-shared environmental influences 56%[49-64%] of variance in diurnal preference, whereas for middle adulthood these estimates were 34%[21-45%] and 66%[55-79%], respectively. Therefore, genetic influences on diurnal preference are attenuated in middle adulthood. Attenuation is likely driven by the increased importance of work and family responsibilities during this life stage, in comparison with younger and older adulthood when these factors may be less influential in determining sleep-wake timing. These findings have implications for studies aimed at identifying specific non-shared environmental influences, as well as molecular genetic studies aimed at identifying specific polymorphisms associated with diurnal preference.

Background: The etiology of chronic fatigue syndrome (CFS) remains unknown. Personality traits influence well-being and may play a role in CFS and unexplained chronic fatigue., Purpose: This study aimed to examine the association of emotional instability and extraversion with chronic fatigue and CFS in a genetically informative sample., Methods: We evaluated 245 twin pairs for two definitions of chronic fatigue. They completed the Neuroticism and Extraversion subscales of the NEO Five Factor Inventory. Using a co-twin control design, we examined the association between personality and chronic fatigue., Results: Higher emotional instability was associated with both definitions of chronic fatigue and was confounded by shared genetics. Lower extraversion was also associated with both definitions of fatigue, but was not confounded by familial factors., Conclusions: Both emotional instability and extraversion are related to chronic fatigue and CFS. Whereas emotional instability and chronic fatigue are linked by shared genetic mechanisms, the relationship with extraversion may be causal and bidirectional.

Objective: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic pain condition with unclear underlying etiology. Our objectives were to determine whether psychological distress was higher in twins with urological symptoms commonly found in IC/PBS than in twins without, and if so, did familial influences contribute to this association., Method: Data from 1165 female twins in a community-based sample were used. Urological symptoms, symptoms of posttraumatic stress disorder (PTSD), depression, anxiety and perceived stress were assessed with standardized questionnaires. Generalized estimating equation (GEE) regression models were used to examine the relationship between psychological distress and urological symptoms., Results: Compared to unaffected twins, twins with urological symptoms were more likely to report PTSD symptoms (OR=3.9; 95% CI=2.6-5.8), depression (OR=3.1; 95% CI=2.0-5.0), anxiety (OR=3.4; 95% CI=2.3-5.2) and perceived stress (OR=3.2; 95% CI=2.1-4.9). After adjusting for familial influences, the within-pair effects remained significant for PTSD symptoms (OR=2.2; 95% CI=1.2-3.8) and perceived stress (OR=2.2; 95% CI=1.2-3.8)., Conclusion: Familial influences partially explained the relationship between indicators of psychological distress and urological symptoms. Future research should examine shared environmental and genetic mechanisms that may further explain this relationship and improve diagnosis and treatment of this unexplained clinical condition., (Published by Elsevier Inc.)

Aims: To determine whether symptoms of post-traumatic stress disorder (PTSD) are related to the pain of temporomandibular disorders (TMD) in a community-based sample of female twin pairs, and if so, to ascertain whether the association is due to the presence of chronic widespread pain (CWP) and familial/genetic factors., Methods: Data were obtained from 630 monozygotic and 239 dizygotic female twin pairs participating in the University of Washington Twin Registry. PTSD symptoms were assessed with the Impact of Events Scale (IES), with scores partitioned into terciles. TMD pain was assessed with a question about persistent or recurrent pain in the face, jaw, temple; in front of the ear; or in the ear during the past 3 months. CWP was defined as pain located in 3 body regions during the past 3 months. Random-effects regression models, adjusted for demographic features, depression, CWP, and familial/genetic factors, were used to examine the relationship between the IES and TMD pain., Results: IES scores were significantly associated with TMD pain (P < .01). Twins in the highest IES tercile were almost 3 times more likely than those in the lowest tercile to report TMD pain, even after controlling for demographic factors, depression, and CWP. After adjustment for familial and genetic factors, the association of IES scores with TMD pain remained significant in dizygotic twins (Ptrend = .03) but was not significant in monozygotic twins (Ptrend = .30)., Conclusion: PTSD symptoms are strongly linked to TMD pain. This association could be partially explained by genetic vulnerability to both conditions but is not related to the presence of CWP. Future research is needed to understand the temporal association of PTSD and TMD pain and the genetic and physiological underpinnings of this relationship.

Previous studies of the association between posttraumatic stress disorder (PTSD) and chronic widespread pain (CWP) or fibromyalgia have not examined the role of familial or genetic factors. The goals of this study were to determine if symptoms of PTSD are related to CWP in a genetically informative community-based sample of twin pairs, and if so, to ascertain if the association is due to familial or genetic factors. Data were obtained from the University of Washington Twin Registry, which contains 1042 monozygotic and 828 dizygotic twin pairs. To assess the symptoms of PTSD, we used questions from the Impact of Events Scale (IES). IES scores were partitioned into terciles. CWP was defined as pain located in 3 body regions lasting at least 1 week during the past 3 months. Random-effects regression models, adjusted for demographic features and depression, examined the relationship between IES and CWP. IES scores were strongly associated with CWP (P<0.0001). Compared to those in the lowest IES tercile, twins in the highest tercile were 3.5 times more likely to report CWP. Although IES scores were associated with CWP more strongly among dizygotic than among monozygotic twins, this difference was not significant. Our findings suggest that PTSD symptoms, as measured by IES, are strongly linked to CWP, but this association is not explained by a common familial or genetic vulnerability to both conditions. Future research is needed to understand the temporal association of PTSD and CWP, as well as the physiological underpinnings of this relationship.

Study Objectives: To better understand the relationships of insomnia, sleepiness, and obesity., Design: Classic twin study., Setting: A community-based twin registry in Washington State., Patients or Participants: One thousand forty-two monozygotic and 828 dizygotic twin pairs participating in the University of Washington Twin Registry., Interventions: N/A., Measurements and Results: Twins were, on average, 32 years old; 61% were women, and 19.5% were obese, defined as a body mass index > or = 28. Insomnia and sleepiness were endorsed by 19.3% and 3.7% of twins, respectively. Twin correlations were higher in monozygotic than dizygotic twins for insomnia (0.47 versus 0.15), sleepiness (0.37 versus 0.14), and obesity (0.82 versus 0.46). Heritability estimates were 57% for insomnia (p < .001; 95% confidence interval 47-63), 38% for sleepiness (p < .01; 95% confidence interval 16-46), and 73% for obesity (p < .001; 95% confidence interval 49-87). Multivariate genetic model fitting revealed that common additive genetic effects comprised 12.8% of the phenotypic correlation between insomnia and sleepiness (p < .01) and 10% of the phenotypic correlation between insomnia and obesity (p < .01). The phenotypic correlation between sleepiness and obesity was not due to common additive genetic effects., Conclusions: Insomnia, sleepiness, and obesity are under strong genetic influence. Common genetic effects were observed between insomnia and both sleepiness and obesity, suggesting shared genetic contributions to these phenomena.

Reports of fatigue preceding cardiac events have recently been confirmed by large prospective studies. To assess for genetic confounding, we investigated prolonged fatigue and cardiovascular disease (CVD) in a cohort of World War II veteran twins. We examined data from a questionnaire mailed to members of the National Academy of Sciences-National Research Council (NAS-NRC) World War II Twins Registry in 1998 and 1999 which included questions on demographics, medical conditions and symptoms of fatigue. Data from twins discordant for prolonged fatigue lasting a month or more were analyzed using conditional logistic regression. Among 1955 twin pairs, 157 monozygotic and 174 dizygotic pairs (mean age 74 years) were discordant for prolonged fatigue. An association was found between prolonged fatigue and a history of myocardial infarction or coronary artery surgery adjusting for age, socioeconomic status, smoking, alcohol use and depression (OR [Odds Ratio]: 2.2; 95% CI: 1.3-4.0). When analyses were performed separately by zygosity, the association was slightly larger for monozygotic (OR: 3.3; 95% CI: 1.2-9.1) than dizygotic twins (OR: 1.9; 95% CI: 0.9-4.0). These data corroborate the association of fatigue with CVD and suggest that it is not influenced by a common genetic factor. Further studies are needed to clarify the relationship and to better understand the biologic mechanisms.

ObjectivePosttraumatic stress disorder (PTSD) is highly comorbid with chronic pain conditions that often co-occur such as migraine headaches, temporomandibular disorder, irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, chronic prostatitis/chronic pelvic pain syndrome, and tension headaches. Using a genetically informative sample, the current study evaluated the genetic and environmental factors contributing to the co-occurrence of PTSD and chronic pain conditions.MethodsData from 4680 male twins in the Vietnam Era Twin Registry were examined. Biometric modeling was used to estimate genetic and environmental variance components and genetic and environmental correlations between PTSD and multiple chronic pain conditions.ResultsHeritabilities were estimated at 43% (95% confidence interval [CI] = 15%-63%) for PTSD and 34% (95% CI = 27%-41%) for the combined history of any one or more pain condition. Specific pain condition heritabilities ranged from 15% (95% CI = 0%-48%) for tension headaches to 41% (95% CI = 27%-54%) for migraine headaches. Environmental influences accounted for the remaining variance in pain conditions. The genetic correlation between PTSD and combined history of any one or more pain condition was rg= 0.61 (95% CI = 0.46-0.89) and ranged for individual pain conditions from rg= 0.44 (95% CI = 0.24-0.77) for migraine headache to rg= 0.75 (95% CI = 0.52-1.00) for tension headaches.ConclusionsPTSD and chronic pain conditions are highly comorbid, and this relationship can be explained by both genetic and environmental overlap. The precise mechanisms underlying these relationships are likely diverse and multifactorial.

ObjectivesChronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by pain and voiding symptoms in the absence of an obvious infection or other cause. CP/CPPS frequently occurs with non-urological chronic overlapping pain conditions (COPCs) of unknown etiology. We conducted a co-twin control study in men discordant for chronic prostatitis (CP), an overarching diagnosis of which approximately 90% is CP/CPPS. The primary aim was to investigate the contribution of familial factors, including shared genetic and common environmental factors, to the comorbidity of CP and COPCs.MethodsData from 6824 male twins in the Vietnam Era Twin Registry were examined to evaluate the association between self-reported lifetime physician diagnosis of CP with COPCs including fibromyalgia, chronic fatigue syndrome, irritable bowel syndrome, temporomandibular disorder, tension headaches, and migraine headaches. Random effects logistic regression models were used and within-pair analyses evaluated confounding effects of familial factors on the associations.ResultsThere were significant associations between CP and all 6 examined COPCs. After adjusting for shared familial influences in within twin pair analyses, the associations for all COPCs diminished but remained significant. Familial confounding was strongest for the association of CP with fibromyalgia and temporomandibular disorder and smallest for irritable bowel syndrome.ConclusionsCP and COPCs are highly comorbid. These associations can be partially explained by familial factors. The mechanisms underlying these relationships are likely diverse and multifactorial. Future longitudinal research can help to further elucidate specific genetic and environmental mechanisms and determine potentially causal relationships between CP and its comorbidities.

ObjectivesHypothalamic-pituitary-adrenal (HPA) axis dysregulation is associated with chronic pain. Studying pain sensitivity and the HPA axis could elucidate the role of stress in chronic pain development, which might be influenced by familial factors, including genes.MethodsAssociations between pain sensitivity and salivary cortisol and familial confounding in these associations were examined in 88 female, community-based twin pairs (75% monozygotic, mean age 29 y). Cortisol was assessed after 0.25 mg dexamethasone (DEX), recovery from 0.25 mg DEX, and after 0.5 mg DEX. Cold pressor task (CPT) pain ratings were obtained at threshold and at tolerance. Conditioned pain modulation (CPM) was examined using thermal heat as the testing stimulus and hot water as the conditioning stimulus. Generalized estimating equation models were used and adjusted for baseline pain rating, age, and other relevant covariates.ResultsAfter controlling for baseline cortisol, greater cortisol suppression following DEX administration and lower recovery cortisol levels were associated with higher pain ratings at tolerance during the CPT (Bs=-2.42 to -17.82; Ps=0.031 to

PurposeSymptoms of urinary irritation, urgency, frequency and obstruction, known as lower urinary tract symptoms, are common in urological practice. However, little is known about the etiology or pathogenesis of lower urinary tract symptoms, especially the relative contributions of genetic and environmental factors to the development of these symptoms. We used a classic twin study design to examine the relative contributions of genetic and environmental factors to the occurrence of lower urinary tract symptoms in middle-aged men.Materials and methodsTwins were members of the Vietnam Era Twin Registry. We used a mail survey to collect data on lower urinary tract symptoms using the I-PSS (International Prostate Symptom Score) instrument. Twin correlations and biometric modeling were used to determine the relative genetic and environmental contributions to variance in I-PSS total score and individual items.ResultsParticipants were 1,002 monozygotic and 580 dizygotic middle-aged male twin pairs (mean age 50.2 years, SD 3.0). Nearly 25% of the sample had an I-PSS greater than 8, indicating at least moderate lower urinary tract symptoms. The heritability of the total I-PSS was 37% (95% CI 32-42). Heritability estimates ranged from 21% for nocturia to 40% for straining, with moderate heritability (34% to 36%) for urinary frequency and urgency.ConclusionsGenetic factors provide a moderate contribution (20% to 40%) to lower urinary tract symptoms in middle-aged men, suggesting that environmental factors may also contribute substantially to lower urinary tract symptoms. Future research is needed to define specific genetic and environmental mechanisms that underlie the development of these symptoms and conditions associated with lower urinary tract symptoms.

Posttraumatic stress disorder (PTSD) and eating disorders (ED) frequently co-occur, but the mechanisms underlying this association remain unclear. EDs are characterized by features of maladaptive eating behaviors including disinhibited eating and cognitive dietary restraint. Identifying the genetic overlap between PTSD symptoms and maladaptive eating behaviors may elucidate biological mechanisms and potential treatment targets. A community sample of 400 same-sex twins (102 monozygotic and 98 dizygotic pairs) completed the PTSD Checklist-Civilian (PCL-C) for PTSD symptoms and the Three-Factor Eating Questionnaire-Reduced (TFEQ-R18) for eating behaviors (uncontrolled eating, emotional eating, and cognitive dietary restraint). We used biometric modeling to examine the genetic and environmental relationships between PCL-C and TFEQ-R18 total and subscales scores. Heritability was estimated at 48% for PTSD symptoms and 45% for eating behavior overall. Bivariate models revealed a significant genetic correlation between PTSD symptoms and eating behavior overall (rg =.34; CI:.07,.58) and Uncontrolled Eating (rg =.53; CI:.24,.84), and a significant environmental correlation between PTSD symptoms and Emotional Eating (re =.30; CI:.12,.45). These findings suggest the influence of common etiology. Future research and clinical efforts should focus on developing integrated treatments. [ABSTRACT FROM AUTHOR]

In 1984, Hrubec and Robinette published what was arguably the first review of the role of twins in medical research. The authors acknowledged a growing distinction between two categories of twin studies: those aimed at assessing genetic contributions to disease and those aimed at assessing environmental contributions while controlling for genetic variation. They concluded with a brief section on recently founded twin registries that had begun to provide unprecedented access to twins for medical research. Here we offer an overview of the twin research that, in our estimation, best represents the field has progress since 1984. We start by summarizing what we know about twinning. We then focus on the value of twin study designs to differentiate between genetic and environmental influences on health and on emerging applications of twins in multiple areas of medical research. We finish by describing how twin registries and networks are accelerating twin research worldwide. [ABSTRACT FROM AUTHOR]

Aims: To determine whether shared genetic influences are responsible for the association between pain from temporomandibular disorders (TMD) and migraine headache. Methods: Data were obtained from 1,236 monozygotic and 570 dizygotic female twin pairs from the University of Washington Twin Registry. TMD pain was assessed with a question about persistent or recurrent pain in the jaw, temple, in front of the ear, or in the ear. The presence of migraine headache was determined by self-report of doctor-diagnosed migraine. Univariate and bivariate structural equation models estimated the components of variance attributable to genetic and environmental influences. Results: The best fitting univariate models indicated that additive genetic effects contributed 27% of the variance in TMD pain (95% confidence interval = 15% to 38%) and 49% of the variance in migraine headache (95% confidence interval = 40% to 57%). The best-fitting bivariate model revealed that 12% of the genetic component of TMD pain is shared with migraine headache. Conclusion: These preliminary findings suggest that the association between TMD pain and migraine headache in women may be partially due to a modest shared genetic risk for both conditions. Future studies can focus on replicating these findings with symptom- and diagnosis-based instruments. [ABSTRACT FROM AUTHOR]

Background: Neural responses to highly energetic food cues are robust and are suppressed by eating. It is not known if neural responsiveness to food cues is an inherited trait and possibly even one that mediates the genetic influences on body weight that have been previously observed. Objective: We investigated the inherited influence on brain responses to high-calorie visual food cues before and after a meal. Design: With the use of a monozygotic twin study design, 21 healthy monozygotic twin pairs consumed a standardized breakfast and, 3.5 h later, underwent the first of 2 functional MRI (fMRI) scans with the use of visual food cues. After the first fMRI session, twins consumed a standardized meal, which was followed by the second fMRI. Serial ratings of appetite and food appeal were obtained. An ad libitum buffet was used to measure total caloric and macronutrient intakes. Intraclass correlations (ICCs) were used to test for inherited influences by comparing whether intrapair similarity was greater than interpair similarity. Results: Body mass index was highly correlated within twin pairs (ICC: 0.96; P < 0.0001). ICCs also showed a strong intrapair similarity for the meal-induced change in hunger (ICC: 0.41; P = 0.03), fullness (ICC: 0.39; P = 0.04), and the appeal of fattening food (ICC: 0.57; P < 0.001). Twins ate a similar number of kilocalories at the buffet (ICC: 0.43; P = 0.02). Before the meal, the global brain activation across regions involved in satiety processing was not more similar in twins than in unrelated individuals. However, significant ICCs were present after the meal (ICC: 0.39; P = 0.04) and for the meal-induced change in activation by high-calorie visual food cues (ICC: 0.52; P < 0.01). Conclusion: Inherited factors influence both satiety perception and the effect of a meal to alter regional brain responses to images of highly energetic food. This trial was registered at clinicaltrials.gov as NCT02483663. [ABSTRACT FROM AUTHOR]

The University of Washington Twin Registry is a unique community-based registry of twin pairs who join specifically to participate in scientific research. It was founded in 2002 to serve as a resource for investigators throughout the scientific community. Current enrollment exceeds 7,200 pairs, and plans are in place to increase enrollment to 10,000 pairs by 2015. In addition to serving as a recruitment base for new research studies, the registry maintains extensive and continually expanding survey data on physical and mental health, as well as a biorepository that includes DNA from more than 8,800 individual twins. The registry is engaged in linking member data to birth records and to diagnostic and procedure variables for hospital-based care provided to members in Washington State. It also incorporates several innovative variables relevant to the built and social environments, which were created by geocoding twin addresses and linking the resulting coordinates to geospatial information systems databases. This combination of existing data and biospecimens, characterizing a group of twins who are willing to participate in research, is a valuable resource for the new wave of twin studies. These include ‘omics’, epigenetics, gene-by-environment interactions, and other novel methods to understand human health. [ABSTRACT FROM AUTHOR]

Background: Studies have found a modest association between depression and obesity, especially in women. Given the substantial genetic contribution to both depression and obesity, we sought to determine whether shared genetic influences are responsible for the association between these two conditions. Methods: Data were obtained from 712 monozygotic and 281 dizygotic female twin pairs who are members of the community-based University of Washington Twin Registry. The presence of depression was determined by self-report of doctor-diagnosed depression. Obesity was defined as body mass index of ≥30 kg/m2, based on self-reported height and weight. Generalized estimating regression models were used to assess the age-adjusted association between depression and obesity. Univariate and bivariate structural equation models estimated the components of variance attributable to genetic and environmental influences. Results: We found a modest phenotypic association between depression and obesity (odds ratio=1.6, 95% confidence interval=1.2–2.1). Additive genetic effects contributed substantially to depression (57%) and obesity (81%). The best-fitting bivariate model indicated that 12% of the genetic component of depression is shared with obesity. Conclusions: The association between depression and obesity in women may be in part due to shared genetic risk for both conditions. Future studies should examine the genetic, environmental, social, and cultural mechanisms underlying the relationship between this association. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: Chronic pain and obesity, and their associated impairments, are major health concerns. We estimated the association of overweight and obesity with 5 distinct pain conditions and 3 pain symptoms, and examined whether familial influences explained these relationships. We used data collected from 3,471 twins in the community-based University of Washington Twin Registry. Twins reported sociodemographic data, current height and weight, chronic pain diagnoses and symptoms, and lifetime depression. Overweight and obese were defined as body mass index of 25.0 to 29.9 kg/m2 and ≥ 30.0 kg/m2, respectively. Generalized estimating equation regression models, adjusted for age, gender, depression, and familial/genetic factors, were used to examine the relationship between chronic pain, and overweight and obesity. Overall, overweight and obese twins were more likely to report low back pain, tension-type or migraine headache, fibromyalgia, abdominal pain, and chronic widespread pain than normal-weight twins after adjustment for age, gender, and depression. After further adjusting for familial influences, these associations were diminished. The mechanisms underlying these relationships are likely diverse and multifactorial, yet this study demonstrates that the associations can be partially explained by familial and sociodemographic factors, and depression. Future longitudinal research can help to determine causality and underlying mechanisms. Perspective: This article reports on the familial contribution and the role of psychological factors in the relationship between chronic pain, and overweight and obesity. These findings can increase our understanding of the mechanisms underlying these 2 commonly comorbid sets of conditions. [Copyright &y& Elsevier]

Objective: We examined the relative contributions of genetic and environmental influences to restrained eating. Method: Restrained eating was assessed by the Restraint Scale in a survey mailed to all twins enrolled in the University of Washington Twin Registry. We used structural equation modeling to estimate genetic and nongenetic contributions to restrained eating. Results: 1,196 monozygotic (MZ), 456 same-sex dizygotic (DZ) twins, and 447 opposite-sex twins were included in analyses. Restraint Scale scores were more closely correlated in MZ twins (rmale = .55, rfemale = .55) than in same-sex DZ twins (rmale = .31, rfemale = .19). Based on structural equation modeling, the estimated heritability for restrained eating, adjusted for body mass index (BMI) and sex, was 43% (95% confidence interval 35–50%). There was little evidence for common environmental effects. Discussion: These results indicate an inherited component to restrained eating. Genes could influence restrained eating directly or through inherited mediators such as personality factors or tendencies to gain weight. © 2009 by Wiley Periodicals, Inc. Int J Eat Disord 2009 [ABSTRACT FROM AUTHOR]

Prolonged fatigue equal to or greater than 1 month duration and chronic fatigue equal to or greater than 6 months duration are both commonly seen in clinical practice, yet little is known about the etiology or epidemiology of either symptom. Chronic fatigue syndrome (CFS), while rarer, presents similar challenges in determining cause and epidemiology. Twin studies can be useful in elucidating genetic and environmental influences on fatigue and CFS. The goal of this article was to use biometrical structural equation twin modeling to examine genetic and environmental influences on fatigue, and to investigate whether these influences varied by gender. A total of 1042 monozygotic (MZ) twin pairs and 828 dizygotic (DZ) twin pairs who had completed the University of Washington Twin Registry survey were assessed for three fatigue-related variables: prolonged fatigue, chronic fatigue, and CFS. Structural equation twin modeling was used to determine the relative contributions of additive genetic effects, shared environmental effects, and individual-specific environmental effects to the 3 fatigue conditions. In women, tetrachoric correlations were similar for MZ and DZ pairs for prolonged and chronic fatigue, but not for CFS. In men, however, the correlations for prolonged and chronic fatigue were higher in MZ pairs than in DZ pairs. About half the variance for both prolonged and chronic fatigue in males was due to genetic effects, and half due to individual-specific environmental effects. For females, most variance was due to individual environmental effects. [ABSTRACT FROM AUTHOR]

Objective. Individuals with chronic fatigue syndrome (CFS) experience many pain symptoms. The present study examined whether pain and fatigue ratings and pain threshold and tolerance levels for cold pain differed between twins with CFS and their cotwins without CFS. Design. Cotwin control design to assess cold pain sensitivity, pain, and fatigue in monozygotic twins discordant for CFS. Patients and Setting. Fifteen monozygotic twin pairs discordant for CFS recruited from the volunteer Chronic Fatigue Twin Registry at the University of Washington. Results. Although cold pain threshold and tolerance levels were slightly lower in twins with CFS than their cotwins without CFS, these differences failed to reach statistical significance. Subjective ratings of pain and fatigue at multiple time points during the experimental protocol among twins with CFS were significantly higher than ratings of pain ( P = 0.003) and fatigue ( P < 0.001) by their cotwins without CFS. Conclusions. These results, while preliminary, highlight the perceptual and cognitive components to the pain experience in CFS. Future studies should focus on examining the heritability of pain sensitivity and the underlying mechanisms involved in the perception of pain sensitivity in CFS. [ABSTRACT FROM AUTHOR]

The University of Washington Twin Registry is a community-based registry of twins identified from the Washington State Department of Licensing. A fortuitous quirk in the Washington State drivers' license and identification number assignment, and collaborative Washington State laws, permitted us to build a statewide registry. Since obtaining approval from the Washington State Attorney General, the Washington State Department of Licensing has provided us with information on over 26,000 newly licensed twins, and we continue to receive computerized records on approximately 80 new twins per week. The University of Washington Twin Registry is assembled by mailing each twin a recruitment packet that includes an information sheet, brochure, brief survey, and nominal gift. Once both members of a twin pair have completed the packet, the pair is enrolled in the registry. As of June 2006, 2287 adult twin pairs have enrolled in the registry; about one half of these are female-female pairs. Among all twins, the average age is 32 years. Based on self-report, 52% of twins are monozygotic, 42% are dizygotic, and zygosity on 6% cannot yet be determined. We also have instituted a clinical protocol for collecting additional data and DNA from all twins participating in research studies requiring an in-person visit. The registry has established policies and procedures to protect the confidentiality of twin data and guidelines for the use of the registry by investigators. Plans for the further growth of the University of Washington Twin Registry and its use are discussed. [ABSTRACT FROM AUTHOR]

: PurposeChronic fatigue syndrome (CFS) is characterized by profound fatigue accompanied by disturbances of sleep, cognition, mood, and other symptoms. Our objective was to describe sleep architecture in CFS-discordant twin pairs.: MethodsWe conducted a co-twin control study of 22 pairs of monozygotic twins where one twin met criteria for CFS and the co-twin was healthy. Twins underwent two nights of polysomnography.: ResultsThe percentage of Stage 3 and REM sleep was greater among the CFS twins than their healthy co-twins (P≤.05 for both), but no other differences in sleep architecture including sleep latency, REM latency, and total sleep time were observed. Compared to their co-twins, CFS twins had higher values for the apnea–hypopnea index and apnea–hypopnea arousal index (P≤.05 for both).: ConclusionThese results do not provide strong evidence for a major role for abnormalities in sleep architecture in CFS. Respiration appears impaired in CFS, but these clinical abnormalities cannot alone account for the prominence of sleep complaints in this illness. The co-twin control methodology highlights the importance of selecting well-matched control subjects. [Copyright &y& Elsevier]

Abstract: Objective: This study examined if associations between body mass index (BMI) and mental and physical health were independent of genetic and familial factors. Method: Data from 2831 twins (66% female) were used in an epidemiological co-twin control design with measures of BMI and mental and physical health outcomes. Generalized estimating equation regressions assessed relationships between BMI and health outcomes controlling for interdependency among twins and demographics. Within-pair regression analyses examined the association of BMI with health outcomes controlling for genetic and familial influences. Results: Adjusted analyses with individual twins found associations in women between BMI and perceived stress (P=.01) and depression (P=.002), and the link between BMI and depression (P=.03) was significant in men. All physical health outcomes were significantly related to BMI. Once genetic and familial factors were taken into account, mental health outcomes were no longer significantly associated with BMI. BMI in women remained related to ratings of physical health (P=.01) and body pain (P=.004), independent of genetic and familial influences. Conclusion: These findings suggest that genetic and familial factors may account for the relationship between increased weight and poor mental health. [Copyright &y& Elsevier]

Abstract: We used a classical twin design and measures of neighborhood walkability and social deprivation, using each twin''s street address, to examine genetic and environmental influences on the residential location of 1389 same-sex pairs from a US community-based twin registry. Within-pair correlations and structural equation models estimated these influences on walkability among younger (ages 18–24.9) and older (ages 25+) twins. Adjusting for social deprivation, walkability of residential location was primarily influenced by common environment with lesser contributions of unique environment and genetic factors among younger twins, while unique environment most strongly influenced walkability, with small genetic and common environment effects, among older twins. Thus, minimal variance in walkability was explained by shared genetic effects in younger and older twins, and confirms the importance of environmental factors in walkability of residential locations. [Copyright &y& Elsevier]

Abstract: We studied whether self-reported intent to exert cognitive control over eating was associated with differences in brain response to food cues, independent of genetic background. Subjects were ten pairs of identical twins in which one twin was a restrained eater and the co-twin was unrestrained, as classified by the Herman and Polivy Restraint Scale. Before and after ingestion of a milkshake, we used functional magnetic resonance imaging to measure brain response to photographs of objects, “fattening” food, and “non-fattening” food. At baseline, restrained eaters had greater activation in the left amygdala and the right thalamus in response to fattening food cues than did their unrestrained co-twins. When restrained eaters drank a milkshake, activation in response to fattening food photographs decreased across multiple brain areas, whereas activation induced by non-fattening food photographs increased. As compared to their unrestrained co-twins, restrained eaters who drank a milkshake had greater decreases in activation by fattening food images in the left amygdala and occipital lobe, and greater increases in activation by non-fattening food images in the medial orbitofrontal cortex. Because of the discordant monozygotic twin study design, the findings provide a rigorous level of support for the hypothesis that adopting an intention to restrain eating alters brain response to food cues. [Copyright &y& Elsevier]

Abstract: Objective: The purpose of the study was to evaluate quantitative sleep electroencephalogram (EEG) frequencies in monozygotic twins discordant for chronic fatigue syndrome. Methods: Thirteen pairs of female twins underwent polysomnography. During the first night, they adapted to the sleep laboratory, and during the second night, their baseline sleep was assessed. Visual stage scoring was conducted on sleep electroencephalographic records according to standard criteria, and power spectral analysis was used to quantify delta through beta frequency bands, processed in 6-s blocks. Data were averaged across sleep stage within each twin and coded for sleep stage and the presence or absence of chronic fatigue syndrome (CFS). A completely within-subjects repeated measure multivariate analysis of variance evaluated twin pairs by frequency band by sleep stage interactions and simple effects. The relationship between alpha and delta EEG was also assessed across twin pairs. Results: No significant differences in spectral power in any frequency band were found between those with CFS and their nonfatigued cotwins. Phasic alpha activity, coupled with delta was noted in five subjects with CFS but was also present in 4/5 healthy twins, indicating this finding likely reflects genetic influences on the sleep electroencephalogram rather than disease-specific sleep pathology. Conclusions: The genetic influences on sleep polysomnography and microarchitecture appear to be stronger than the disease influence of chronic fatigue syndrome, despite greater subjective sleep complaint among the CFS twins. EEG techniques that focus on short duration events or paradigms that probe sleep regulation may provide a better description of sleep abnormalities in CFS. [Copyright &y& Elsevier]

Abstract: Background: : Previous work using quantified EEG has suggested that brain activity in individuals with chronic fatigue syndrome (CFS) and normal persons differs. Our objective was to investigate if specific frequency band-pass regions and spatial locations are associated with CFS using low-resolution electromagnetic brain tomography (LORETA). Methods: : We conducted a co-twin control study of 17 pairs of monozygotic twins where 1 twin met criteria for CFS and the co-twin was healthy. Twins underwent an extensive battery of tests including a structured psychiatric interview and a quantified EEG. Eyes closed EEG frequency-domain analysis was computed and the entire brain volume was compared of the CFS and healthy twins using a multiple comparison procedure. Results: : Compared with their healthy co-twins, twins with CFS differed in current source density. The CFS twins had higher delta in the left uncus and parahippocampal gyrus and higher theta in the cingulate gyrus and right superior frontal gyrus. Conclusions: : These findings suggest that neurophysiological activity in specific areas of the brain may differentiate individuals with CFS from those in good health. The study corroborates that slowing of the deeper structures of the limbic system is associated with affect. It also supports the neurobiological model that the right forebrain is associated with sympathetic activity and the left forebrain with the effective management of energy. These preliminary findings await replication. [Copyright &y& Elsevier]