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The purpose of this review is to provide a detailed and updated description of the FinnTwin16 (FT16) study and its future directions. The Finnish Twin Cohort comprises three different cohorts: the Older Twin Cohort established in the 1970s and the FinnTwin12 and FT16 initiated in the 1990s. FT16 was initiated in 1991 to identify the genetic and environmental precursors of alcoholism, but later the scope of the project expanded to studying the determinants of various health-related behaviors and diseases in different stages of life. The main areas addressed are alcohol use and its consequences, smoking, physical activity, overall physical health, eating behaviors and eating disorders, weight development, obesity, life satisfaction and personality. To date, five waves of data collection have been completed and the sixth is now planned. Data from the FT16 cohort have contributed to several hundred studies and many substudies, with more detailed phenotyping and collection of omics data completed or underway. FT16 has also contributed to many national and international collaborations.

Objective We assessed the detection, treatment and outcomes of DSM-5 eating disorders in a nationwide community setting. Method The FinnTwin12 cohort comprises twins born in 1983-1987 in Finland (n = 5,600), with follow-up starting at age 12. We outline treatment and outcomes of the 127 females and 15 males diagnosed with a lifetime DSM-5 eating disorder in interviews conducted for a subsample (n = 1,347) in their early 20s. Results Only 45 (32%) of those diagnosed with eating disorder in the interviews had their condition detected in healthcare, and even fewer received treatment (30% of females, 13% of males). Anorexia nervosa (AN), bulimia nervosa, and atypical AN were detected and treated more often than other eating disorders. Five years after disease onset, 41% of those diagnosed had recovered. There were no statistically significant differences in the course of different eating disorders (log-rank p = 0.66) but the outcome was more favourable among males (log-rank p = 0.008). The likelihood of 5-year recovery did not differ between those who had and who had not received treatment (41.1% vs. 40.5%, log-rank p = 0.66). Conclusion Although eating disorders are common and symptoms are persistent for many, they remain under-diagnosed and under-treated. In real-world settings, effectiveness of provided treatments may be limited.

Aims/hypothesis Metabolomics technologies have identified numerous blood biomarkers for type 2 diabetes risk in case−control studies of middle-aged and older individuals. We aimed to validate existing and identify novel metabolic biomarkers predictive of future diabetes in large cohorts of young adults. Methods NMR metabolomics was used to quantify 229 circulating metabolic measures in 11,896 individuals from four Finnish observational cohorts (baseline age 24–45 years). Associations between baseline metabolites and risk of developing diabetes during 8–15 years of follow-up (392 incident cases) were adjusted for sex, age, BMI and fasting glucose. Prospective metabolite associations were also tested with fasting glucose, 2 h glucose and HOMA-IR at follow-up. Results Out of 229 metabolic measures, 113 were associated with incident type 2 diabetes in meta-analysis of the four cohorts (ORs per 1 SD: 0.59–1.50; pn-6 fatty acid (OR 0.75) and non-esterified cholesterol in large HDL particles (OR 0.59). The metabolic biomarkers were more strongly associated with deterioration in post-load glucose and insulin resistance than with future fasting hyperglycaemia. A multi-metabolite score comprised of phenylalanine, non-esterified cholesterol in large HDL and the ratio of cholesteryl ester to total lipid in large VLDL was associated with future diabetes risk (OR 10.1 comparing individuals in upper vs lower fifth of the multi-metabolite score) in one of the cohorts (mean age 31 years). Conclusions/interpretation Metabolic biomarkers across multiple molecular pathways are already predictive of the long-term risk of diabetes in young adults. Comprehensive metabolic profiling may help to target preventive interventions for young asymptomatic individuals at increased risk.

Recently, 2 transcriptome-wide studies identified 40 genes that were differentially expressed in relation to blood pressure. However, to what extent these BP-related gene expression signatures and their associations with BP are driven by genetic or environmental factors has not been investigated. In this study of 391 twins (193 twin pairs and 5 singletons; age 55–69 years; 40% male; 57% monozygous) recruited from the Finnish Twin Cohort, transcriptome-wide data on peripheral leukocytes were obtained using the Illumina HT12 V4 array. Our transcriptome-wide analysis identified 1 gene ( MOK [MAPK/MAK/MRK overlapping kinase], P =7.16×10 − 8 ) with its expression levels associated with systolic BP at the cutoff of false-discovery rate P =1.02×10 − 5 ). Out of the 40 genes previously reported, 12 genes could be replicated in the twin cohort with false-discovery rate MOK expression, and 100% of the phenotypic association of systolic and diastolic BP with CD97 (cluster of differentiation 97), TIPARP (TCDD-inducible poly[ADP-ribose] polymerase), and TPPP3 expression could be explained by genetic factors shared in common. In this study of adult twins, we identified one more gene, MOK , with its expression level associated with BP, and replicated several previously identified signals. Our study further provides new insights into the genetic and environmental sources of BP-related gene expression signatures.

Background: Weighted hula-hoops have gained popularity, but whether they indeed reshape the trunk or have beneficial metabolic effects in overweight subjects is unknown. Objectives: To determine effects of hula-hooping and walking matched for energy expenditure on android fat %, trunk muscle mass, and metabolic parameters in a randomized cross-over study. Design: We recruited 55 overweight nondiabetic subjects, who were randomized to hula-hooping (HULA) for 6 weeks using a 1.5-kg weighted hula-hoop followed by walking (WALK) for another 6 weeks or vice versa. The increments in energy expenditure were similar by HULA and WALK. Body composition (dual-energy X-ray absorptiometry) and metabolic parameters were measured at baseline and after HULA and WALK. The primary endpoint was the change in fat % in the android region. Results: A total of 53subjects (waist 92 ± 1 cm, body mass index 28 ± 1 kg/m2) completed the study. Body weight changed similarly (–0.6 ± 0.2 vs. –0.5 ± 0.2 kg, nonsignificant; HULA vs. WALK). During the intervention the subjects hula-hooped on average 12.8 ± 0.5 min/day and walked 9,986 ± 376 steps/day. The % fat in the android region decreased significantly by HULA but not by WALK (between-group change p < 0.001). Trunk muscle mass increased more by HULA than by WALK (p < 0.05). Waist circumference decreased more by HULA than by WALK (–3.1 ± 0.3 cm vs. –0.7 ± 0.4 cm, p < 0.001; HULA vs. WALK). WALK but not HULA significantly lowered systolic blood pressure and increased HDL cholesterol while HULA significantly decreased LDL cholesterol. Conclusions: Hula-hooping with a weighted hula-hoop can be used to decrease abdominal fat % and increase trunk muscle mass in overweight subjects. Its LDL lowering effect resembles that described for resistance training.

Background: We assessed whether the Eating Disorder Inventory (EDI) is suitable for screening binge eating disorder (BED) in young women. Method: Young women (N = 2825) from the 1975-79 birth cohorts of Finnish twins were assessed by questionnaires, including subscales of the EDI. For a subset of women (N = 548), we established DSM-5 diagnoses of BED; 16 women had lifetime BED. We compared screening properties of the EDI scales using receiver operating characteristic (ROC) analysis, determined optimal cutoff points, and calculated sensitivities and specificities. Results: The best screen for DSM-5 BED was the global score of three subscales (Bulimia, Drive for Thinness, Body Dissatisfaction) with an area under the curve (AUC) of 0.86. Its sensitivity was 87% and specificity 76% at cutoff >= 21. Three individual subscales had acceptable screening properties: Bulimia (AUC 0.83; sensitivity 80%, specificity 78% at cutoff >= 2), Drive For Thinness (AUC 0.82; sensitivity 87%, specificity 72% at cutoff >= 7), and Body Dissatisfaction (AUC 0.81; sensitivity 93%, specificity 60% at cutoff >= 8). Conclusion: The EDI performed well as a screening tool for BED in our community-based sample of young twin women. Future studies should assess its value in other populations and in clinical settings. (C) 2016 Elsevier Ltd. All rights reserved.

Objective Binge eating disorder (BED) is a clinical eating disorder that is strongly and bidirectionally related to overweight and obesity. Little is known about how subclinical features of BED relate to weight development in adolescence and young adulthood. Method Women (n = 2825) and men (n = 2423) from the community-based longitudinal FinnTwin16 cohort participated. Seven eating-related cognitions and behaviors similar to the defining features of BED were extracted from the Eating Disorder Inventory-2 and were assessed at a mean age of 24. We used linear mixed models to assess the association of features of BED with BMI trajectories across four waves of data collection (mean ages 16, 17, 18, and 24). Results The number of features of BED at wave 4 (age 24) was significantly associated with BMI from age 16 years onwards. Those reporting more features of BED had gained more weight throughout adolescence and into their twenties. Conclusions Features of BED in young adulthood were preceded by steeper BMI trajectories in adolescence. A higher number of features were consistently associated with higher BMI and more weight gain.

Objectives To assess factors associated with successful weight maintenance over ten years in a prospective general population sample of young adults. Material and methods Our study comprised 2452 women and 2227 men born in 1975–1979 (mean age at baseline 24 years, attrition 27.1%). Weight maintenance was defined as weight maintained within ±5% of baseline body mass index (BMI). We examined the role of various sociodemographic and lifestyle factors in successful weight maintenance. Results Relatively few young adults were able to maintain their weight over ten years (28.6% of women vs. 23.0% of men); net weight loss was uncommon (7.5% and 3.8%). Most participants gained weight (mean annual weight gain was 0.9 kg in women and 1.0 kg in men). Among women, exercise was associated with successful weight maintenance, but having two or more children, frequent use of sweet drinks, irregular eating, history of dieting (intentional weight loss) and low life satisfaction were associated with weight gain. Among men, higher baseline BMI and higher education were associated with successful weight maintenance, whereas irregular eating, history of dieting and smoking were associated with weight gain. Conclusions Only about a quarter of young adults were able to resist weight gain. Regular eating and having no history of dieting were associated with successful weight maintenance in young women and men.

OBJECTIVE: The risk of certain psychiatric disorders is elevated among immigrants. To date, no population studies on immigrant health have addressed eating disorders. We examined whether risk of eating disorders in first- and second-generation immigrants differs from native-born Danes and Swedes.METHOD: All individuals born 1984-2002 (Danish cohort) and 1989-1999 (Swedish cohort) and residing in the respective country on their 10th birthday were included. They were followed up for the development of eating disorders based on out-patient and in-patient data.RESULTS: The risks of all eating disorder types were lower among first-generation immigrants compared to the native populations: Incidence-rate ratio (95% confidence interval) was 0.39 (0.29, 0.51) for anorexia nervosa, 0.60 (0.42, 0.83) for bulimia nervosa, and 0.62 (0.47, 0.79) for other eating disorders in Denmark and 0.27 (0.21, 0.34) for anorexia nervosa, 0.30 (0.18, 0.51) for bulimia nervosa, and 0.39 (0.32, 0.47) for other eating disorders in Sweden. Likewise, second-generation immigrants by both parents were at lower risk, whereas those with only one foreign-born parent were not.CONCLUSION: The decreased risk of eating disorders among immigrants is opposite to what has been observed for other psychiatric disorders, particularly schizophrenia. Possible explanations include buffering sociocultural factors and underdetection in health care.

Binge eating disorder (BED) is associated with high levels of obesity and psychological suffering, but little is known about 1) the distribution of features of BED in the general population and 2) their consequences for weight development and psychological distress in young adulthood. We investigated the prevalence of features of BED and their association with body mass index (BMI) and psychological distress among men (n = 2423) and women (n = 2825) from the longitudinal community-based FinnTwin16 cohort (born 1975-1979). Seven eating-related cognitions and behaviors similar to the defining features of BED were extracted from the Eating Disorder Inventory-2 and were assessed at a mean age of 24. BMI and psychological distress, measured with the General Health Questionnaire, were assessed at ages 24 and 34. We assessed prevalence of the features and their association with BMI and psychological distress cross-sectionally and prospectively. More than half of our participants reported at least one feature of BED; clustering of several features in one individual was less common, particularly among men. The most frequently reported feature was 'stuffing oneself with food', whereas the least common was 'eating or drinking in secrecy'. All individual features of BED and their clustering particularly were associated with higher BMI and more psychological distress cross-sectionally. Prospectively, the clustering of features of BED predicted increase in psychological distress but not additional weight gain when baseline BMI was accounted for. In summary, although some features of BED were common, the clustering of several features in one individual was not. The features were cumulatively associated with BMI and psychological distress and predicted further increase in psychological distress over ten years of follow-up. (C) 2016 Published by Elsevier Ltd.

Since medieval times, an association between religiosity and anorexia nervosa has been suggested, but few systematic studies exist. This study examines in a nationwide setting whether personal or family religiosity is associated with lifetime anorexia nervosa among women in adolescence and early adulthood. Women (N = 2,825) from the 1975 to 1979 birth cohorts of Finnish twins were screened for lifetime DSM-5 anorexia nervosa (N = 92). Parental religiosity was assessed by self-report when the women were aged 16 years. The women self-reported their religiosity at ages 16 and 22 to 27 years. Parental religiosity did not increase the risk of lifetime anorexia nervosa, and neither did religiosity of the women themselves in adolescence. In early adulthood, a J-shaped curve was compatible with the data, indicating increased risk both at low and high levels of religiosity, but this result was statistically non-significant. Religiosity was weakly negatively correlated with body dissatisfaction. There was some suggestive evidence for socioregional variation in the association of religiosity with lifetime anorexia nervosa. In this first population study to directly address religiosity and anorexia nervosa, no evidence was found for a significant association of religiosity with anorexia nervosa either at the personal or family level. Some regional differences are possible. A modest protective association of religiosity with body dissatisfaction is also possible. Despite compelling case descriptions of "holy anorexia," religiosity does not appear to be a central factor in the development of anorexia nervosa in Finland, a highly secularized Christian country.

Eating disorders - anorexia nervosa, bulimia nervosa, and binge eating disorder - affect numerous Europeans. This narrative review summarizes European studies on their prevalence, incidence, comorbidity, course, consequences, and risk factors published in 2015 and the first half of 2016.Anorexia nervosa is reported by1-4%, bulimia nervosa1-2%, binge eating disorder1-4%, and subthreshold eating disorders by 2-3% of women in Europe. Of men, 0.3-0.7% report eating disorders. Incidences of anorexia appear stable, whereas bulimia may be declining. Although the numbers of individuals receiving treatment have increased, only about one-third is detected by healthcare. Over 70% of individuals with eating disorders report comorbid disorders: anxiety disorders (50%), mood disorders (40%), self-harm (20%), and substance use (10%) are common. The long-term course of anorexia nervosa is favorable for most, but a substantial minority of eating disorder patients experience longstanding symptoms and somatic problems. The risk of suicide is elevated. Parental psychiatric disorders, prenatal maternal stress, various family factors, childhood overweight, and body dissatisfaction in adolescence increase the risk of eating disorders.Eating disorders are relatively common disorders that are often overlooked, although they are associated with high comorbidity and serious health consequences.

To examine the occurrence, course, and clinical picture of the DSM-5 residual categories 'Other Specified Feeding or Eating Disorder' (OSFED) and 'Unspecified Feeding or Eating Disorder' (UFED), to describe potential subtypes, and to evaluate whether the subdivision of the residual category appears meaningful.We screened women from the 1975-79 birth cohorts of Finnish twins (N = 2825) for lifetime eating disorders using questionnaires and the SCID interview. This analysis characterizes women who reported clinically significant eating disorder symptoms but did not fulfill diagnostic criteria for DSM-5 anorexia nervosa (AN), bulimia nervosa (BN), or binge eating disorder (BED).Thirty-eight women (21% of those with an eating disorder) fell in the residual OSFED/UFED category. A third of them (N = 14) fulfilled OSFED criteria, whereas two thirds (N = 24) fell in the UFED category. The lifetime prevalence of OSFED/UFED was 1.5% (95% CI 1.1-2.0%), less than half of the prevalence of DSM-IV eating disorder not otherwise specified (EDNOS). The mean age of onset of OSFED/UFED was 18 years, median duration of symptoms was two years, and the 5-year probability of recovery was 60%. Over a third of women with OSFED/UFED suffered from comorbid psychiatric disorders. Both residual categories were clinically heterogeneous and included atypical forms of AN, BN, and BED.Applying the DSM-5 criteria in a community sample of young women more than halved the occurrence of residual eating disorder diagnoses, but resulted in two instead of one clinically heterogeneous residual categories. Nevertheless, residual eating disorders were associated with considerable clinical severity. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:1010-1017).

The definition of anorexia nervosa was revised for the Fifth Edition of the Diagnostic and Statistical Manual (DSM-5). We examined the impact of these changes on the prevalence and prognosis of anorexia nervosa. In a nationwide longitudinal study of Finnish twins born 1975-1979, the women (N = 2825) underwent a 2-stage screening for eating disorders at mean age 24. Fifty-five women fulfilled DSM-IV criteria for lifetime anorexia nervosa. When we recoded the interviews using DSM-5 criteria, we detected 37 new cases. We contrasted new DSM-5 vs. DSM-IV cases to assess their clinical characteristics and prognosis. We also estimated lifetime prevalences and incidences and tested the association of minimum BMI with prognosis. We observed a 60% increase in the lifetime prevalence of anorexia nervosa using the new diagnostic boundaries, from 2.2% to 3.6%. The new cases had a later age of onset (18.8 y vs. 16.5, p = 0.002), higher minimum BMI (16.9 vs. 15.5 kg/m(2), p = 0.0004), a shorter duration of illness (one year vs. three years, p = 0.002), and a higher 5-year probability or recovery (81% vs. 67%, p = 0.002). Minimum BMI was not associated with prognosis. It therefore appears that the substantial increase in prevalence of anorexia nervosa is offset by a more benign course of illness in new cases. Increased diagnostic heterogeneity underscores the need for reliable indicators of disease severity. Our findings indicate that BMI may not be an ideal severity marker, but should be complemented by prognostically informative criteria. Future studies should focus on identifying such factors in prospective settings. (C) 2016 Elsevier Ltd. All rights reserved.

(shared first authorship) PURPOSE: The aim of this study was to investigate genetic and environmental influences on different aspects of physical activity in young, adult twins. METHODS: We studied 1274 Finnish twins with a mean age of 22.4 years, from the population-based FinnTwin12 study. Physical activity was assessed with the Baecke questionnaire, yielding four indexes: sport index, leisure-time activity index, work index and total score. Quantitative genetic analyses based on linear structural equations were used to estimate the contribution of genetic and environmental factors on these physical activity traits. RESULTS: The overall heritability estimates were 64% (95% CI 0.56-0.70%) for sports activity, 41% (95% CI 0.31-0.51%) for leisure-time activity excluding sports, 56% (95% CI 0.48-0.63%) for physical activity at work, and 54% (95% CI 0.45-0.62%) for total physical activity. Unique environmental factors accounted for the rest of the trait variances. We did not find evidence for common environmental or dominant genetic influences. The heritability estimates did not differ between men and women and no sex-specific genetic factors were found. Sports activity and leisure-time activity excluding sports were associated (r=0.27) and additive genetic factors explained 57% of their association. CONCLUSION: Our results suggest that genetic factors contribute significantly to physical activity levels in young adults and that sports activity is under stronger genetic influence than leisure-time physical activity excluding sports. We also concluded that physical activity at work does not seem to be associated with sports activities or other leisure-time physical activity at this age. Language: en

Eating disorders and alcohol use disorders often co-occur, but few prospective studies have examined their relationship. Using a large population-based twin sample, we investigated how the drinking behaviors of women with lifetime eating disorders unfold from adolescence to adulthood.We identified 182 women with a lifetime eating disorder assessed at mean age 24, including 92 women with DSM-5 anorexia nervosa and 58 women with DSM-5 bulimia nervosa, from the 1975-1979 birth cohorts of Finnish twins (N = 2,825 women). Frequency of drinking and intoxicating were assessed at ages 16, 24, and 34. Drinking problems were assessed at ages 24 and 34 by the Malmö-modified Michigan Alcohol Screening Test (Mm-Mast) and the Rutgers Alcohol Problem Index (RAPI).At age 16, proportionately more women with eating disorders reported being severely intoxicated when they last drank (25% vs.16%, P = 0.001), and at both surveys in adulthood, they reported more frequent intoxication and more alcohol-related problems than their unaffected peers. Those who had recovered from their eating disorder at age 24 still reported more alcohol-related problems in their 30s than did other women. The age of drinking onset, number of monthly drinking days, or frequency of intoxication in adolescence did not differ between women with lifetime eating disorders and unaffected women.Women with eating disorders scored higher than their unaffected peers on scales measuring alcohol dependence, alcohol-related problems, and intoxication. These differences persisted from mid-adolescence into young adulthood. Women with eating disorders should be assessed routinely for drinking behaviors. © 2016 Wiley Periodicals, Inc. (Int J Eat Disord 2016; 49:563-571).

To quantify weight ideals of young adults and to examine whether the discrepancy between actual and ideal weight is associated with 10-year body mass index (BMI) change in the population.This study comprised 4,964 adults from the prospective population-based FinnTwin16 study. They reported their actual and ideal body weight at age 24 (range 22-27) and 10 years later (attrition 24.6%). The correlates of discrepancy between actual and ideal body weight and the impact on subsequent BMI change were examined.The discrepancy between actual and ideal weight at 24 years was on average 3.9 kg (1.4 kg/m(2) ) among women and 1.2 kg (0.4 kg/m(2) ) among men. On average, participants gained weight during follow-up irrespective of baseline ideal weight: women ¯x = +4.8 kg (1.7 kg/m(2) , 95% CI 1.6-1.9 kg/m(2) ), men ¯x = +6.3 kg (2.0 kg/m(2) , 95% CI 1.8-2.1 kg/m(2) ). Weight ideals at 24 years were not correlated with 10-year weight change. At 34 years, just 13.2% of women and 18.9% of men were at or below the weight they had specified as their ideal weight at 24 years. Women and men adjusted their ideal weight upward over time.Irrespective of ideal weight at baseline, weight gain was nearly universal. Weight ideals were shifted upward over time.

To assess the population prevalence and incidence of binge eating disorder (BED) among young women.In a nationwide longitudinal study of Finnish twins born 1975-1979, the women participated in five surveys from age 16 until their mid-thirties. At Wave 4 (mean age 24 years), the women (N = 2,825) underwent a 2-stage screening for eating disorders. We assessed the lifetime prevalence, incidence, and clinical characteristics of DSM-5 BED.We detected 16 women who met DSM-5 criteria for BED, yielding a lifetime prevalence of 0.7% (95% confidence interval [CI] 0.4-1.2%). The incidence of BED among women between 10 and 24 years of age was 35 (95% CI 20-60) per 100,000 person-years. The mean age of onset of BED was 19 years (range 13-27 years). Of the cases, 13/16 (81%) were currently ill. Duration of illness at the time of assessment ranged from less than a year to 13 years (median 6 years). Of women with BED, only two had a history of other eating disorders, but six had lifetime major depressive disorder. Two-thirds of the women with BED belonged to the highest weight quartile at age 16, and their mean BMI at age 22-27 year was 26.2 kg/m(2) (range 22.1-32.5 kg/m(2)).Incident BED as defined by DSM-5 was relatively rare among younger women and was often preceded by relative overweight. BED often occurred without a history of other eating disorders, but comorbidity with major depressive disorder was common.

Few studies have assessed outcomes of anorexia nervosa (AN) outside clinical settings. We aimed to assess mortality, recovery, and socio-demographic outcomes of AN in a community sample.Women in the nationwide FinnTwin16 cohort (born 1975-1979) were followed for 10 years after baseline diagnostic assessment (mean age at follow-up 34 years, N = 2188). We compared women with lifetime DSM-IV AN (N = 40) with unaffected women from the same cohort.None of the women with AN had died and 88% were weight-recovered (BMI ≥ 18.5 kg/m(2) ), but their mean BMI (22.0 kg/m(2) ) was lower than among unaffected women (24.0 kg/m(2) , p = 0.008). University degrees (38 vs. 29%, p = 0.26), sickness absence during the past year (median 5 vs. 3 days, p = 0.21), or unemployment or disability pension (5 vs. 4%, p = 0.62) did not significantly differ between AN probands and their unaffected peers. More women with AN were still studying (15 vs. 4%, p = 0.003), and half of them had children, as compared to 66% of unaffected women (p = 0.05).The long-term prognosis of AN in the community appears promising. Weight-restoration is common and socio-demographic outcomes are generally favorable. However, women with a history of AN may be less likely to have children.

The association between eating disorders and migraine remains unclear.We identified women with lifetime diagnoses of anorexia nervosa (AN) (N = 55) and bulimia nervosa (BN) (N = 60) and their co-twins from the FinnTwin16 cohort born in 1975-1979 (N = 2,825 women). Eating disorder and major depressive disorder (MDD) diagnoses were obtained from clinical interviews and data on migraine by self-report questionnaire. The women with eating disorders were compared with their unaffected co-twins and with unrelated women from the same birth cohorts.The prevalence of migraine was 12% in the general female population, but 22% for both AN and BN (odds ratio 2.0, p = .04). The prevalence of MDD was high in women with an eating disorder (42%). MDD was strongly associated with migraine (odds ratio 3.0, p .0001) and explained the association between eating disorders and migraine. The highest migraine prevalence (36%) was found in women with both an eating disorder and MDD. Pairwise twin analyses also supported the clustering of migraine, MDD and eating disorders.Women with a lifetime diagnosis of an eating disorder were twice as likely to report a history of migraine as unrelated women from the same cohort; this relationship was explained by comorbid MDD.

Exercise behavior, cardiorespiratory fitness, and obesity are strongly influenced by genetic factors. By studying young adult twins, we examined to what extent these interrelated traits have shared genetic and environmental etiologies. We studied 304 twin individuals selected from the population-based FinnTwin16 study. Physical activity was assessed with the Baecke questionnaire, yielding three indexes: sport index, leisure-time index, and work index. In this study, we focused on sport index, which describes sports participation. Body composition was determined using dual-energy X-ray absorptiometry and cardiorespiratory fitness using a bicycle ergometer exercise test with gas exchange analysis. The Baecke sport index was associated with high maximal oxygen uptake adjusted for lean body mass (V̇o2max[adj]) ( r = 0.40), with low body fat percentage (BF%) ( r = −0.44) and low waist circumference (WC) ( r = −0.29). Heritability estimates for the key traits were as follows: 56% for sport index, 71% for V̇o2max[adj], 77% for body mass index, 66% for WC, and 68% for BF%. The association between sport index and V̇o2max was mostly explained by genetic factors (70%), as were both the association between sport index and BF% (71%) and that between sport index and WC (59%). Our results suggest that genetic factors explain a considerable part of the associations between sports participation, cardiorespiratory fitness, and obesity.

Lung function measures are heritable traits that predict population morbidity and mortality and are essential for the diagnosis of chronic obstructive pulmonary disease (COPD). Variations in many genes have been reported to affect these traits, but attempts at replication have provided conflicting results. Recently, we undertook a meta-analysis of Genome Wide Association Study (GWAS) results for lung function measures in 20,288 individuals from the general population (the SpiroMeta consortium). OBJECTIVES: To comprehensively analyse previously reported genetic associations with lung function measures, and to investigate whether single nucleotide polymorphisms (SNPs) in these genomic regions are associated with lung function in a large population sample. METHODS: We analysed association for SNPs tagging 130 genes and 48 intergenic regions (+/-10 kb), after conducting a systematic review of the literature in the PubMed database for genetic association studies reporting lung function associations. The analysis included 16,936 genotyped and imputed SNPs. No loci showed overall significant association for FEV(1) or FEV(1)/FVC traits using a carefully defined significance threshold of 1.3×10(-5). The most significant loci associated with FEV(1) include SNPs tagging MACROD2 (P = 6.81×10(-5)), CNTN5 (P = 4.37×10(-4)), and TRPV4 (P = 1.58×10(-3)). Among ever-smokers, SERPINA1 showed the most significant association with FEV(1) (P = 8.41×10(-5)), followed by PDE4D (P = 1.22×10(-4)). The strongest association with FEV(1)/FVC ratio was observed with ABCC1 (P = 4.38×10(-4)), and ESR1 (P = 5.42×10(-4)) among ever-smokers.CONCLUSIONS: Polymorphisms spanning previously associated lung function genes did not show strong evidence for association with lung function measures in the SpiroMeta consortium population. Common SERPINA1 polymorphisms may affect FEV(1) among smokers in the general population.

Pulmonary function measures are heritable traits that predict morbidity and mortality and define chronic obstructive pulmonary disease (COPD). We tested genome-wide association with forced expiratory volume in 1 s (FEV(1)) and the ratio of FEV(1) to forced vital capacity (FVC) in the SpiroMeta consortium (n = 20,288 individuals of European ancestry). We conducted a meta-analysis of top signals with data from direct genotyping (n < or = 32,184 additional individuals) and in silico summary association data from the CHARGE Consortium (n = 21,209) and the Health 2000 survey (n < or = 883). We confirmed the reported locus at 4q31 and identified associations with FEV(1) or FEV(1)/FVC and common variants at five additional loci: 2q35 in TNS1 (P = 1.11 x 10(-12)), 4q24 in GSTCD (2.18 x 10(-23)), 5q33 in HTR4 (P = 4.29 x 10(-9)), 6p21 in AGER (P = 3.07 x 10(-15)) and 15q23 in THSD4 (P = 7.24 x 10(-15)). mRNA analyses showed expression of TNS1, GSTCD, AGER, HTR4 and THSD4 in human lung tissue. These associations offer mechanistic insight into pulmonary function regulation and indicate potential targets for interventions to alleviate respiratory disease.

Both obesity and exercise behavior are influenced by genetic and environmental factors. However, whether obesity and physical inactivity share the same genetic vs environmental etiology has rarely been studied. We therefore analyzed these complex relationships, and also examined whether physical activity modifies the degree of genetic influence on body mass index (BMI) and waist circumference (WC).The FinnTwin16 Study is a population-based, longitudinal study of five consecutive birth cohorts (1975-1979) of Finnish twins. Data on height, weight, WC and physical activity of 4343 subjects at the average age of 25 (range, 22-27 years) years were obtained by a questionnaire and self-measurement of WC. Quantitative genetic analyses based on linear structural equations were carried out by the Mx statistical package. The modifying effect of physical activity on genetic and environmental influences was analyzed using gene-environment interaction models.The overall heritability estimates were 79% in males and 78% in females for BMI, 56 and 71% for WC and 55 and 54% for physical activity, respectively. There was an inverse relationship between physical activity and WC in males (r = -0.12) and females (r=-0.18), and between physical activity and BMI in females (r = -0.12). Physical activity significantly modified the heritability of BMI and WC, with a high level of physical activity decreasing the additive genetic component in BMI and WC.Physically active subjects were leaner than sedentary ones, and physical activity reduced the influence of genetic factors to develop high BMI and WC. This suggests that the individuals at greatest genetic risk for obesity would benefit the most from physical activity.

Defects in expression of genes of oxidative phosphorylation in mitochondria have been suggested to be a key pathophysiological feature in familial insulin resistance. We examined whether such defects can arise from lifestyle-related factors alone. Fourteen obesity-discordant (BMI difference 5.2 ± 1.8 kg/m2) and 10 concordant (1.0 ± 0.7 kg/m2) monozygotic (MZ) twin pairs aged 24–27 yr were identified among 658 MZ pairs in the population-based FinnTwin16 study. Whole body insulin sensitivity was measured using the euglycemic hyperinsulinemic clamp technique. Transcript profiles of mitochondrial genes were compared using microarray data of fat biopsies from discordant twins. Body composition of twins was determined using DEXA and maximal oxygen uptake (V̇o2max) and working capacity (Wmax) using a bicycle ergometer exercise test with gas exchange analysis. The obese cotwins had lower insulin sensitivity than their nonobese counterparts (M value 6.1 ± 2.0 vs. 9.2 ± 3.2 mg·kg LBM−1·min−1, P < 0.01). Transcript levels of genes involved in the oxidative phosphorylation pathway (GO:0006119) in adipose tissue were lower ( P < 0.05) in the obese compared with the nonobese cotwins. The obese cotwins were also less fit, as measured by V̇o2max (50.6 ± 6.5 vs. 54.2 ± 6.4 ml·kg LBM−1·min−1, for obese vs. nonobese, P < 0.05), Wmax (3.9 ± 0.5 vs. 4.4 ± 0.7 W/kg LBM, P < 0.01) and also less active, by the Baecke leisure time physical activity index (2.8 ± 0.5 vs. 3.3 ± 0.6, P < 0.01). This implies that acquired poor physical fitness is associated with defective expression of the oxidative pathway components in adipose tissue mitochondria.