Both genetic and environmental factors are involved in the etiology of obesity and the associated lipid disturbances. We determined whether acquired obesity is associated with changes in global serum lipid profiles independent of genetic factors in young adult monozygotic (MZ) twins. 14 healthy MZ pairs discordant for obesity (10 to 25 kg weight difference) and ten weight concordant control pairs aged 24-27 years were identified from a large population-based study. Insulin sensitivity was assessed by the euglycemic clamp technique, and body composition by DEXA (% body fat) and by MRI (subcutaneous and intra-abdominal fat). Global characterization of lipid molecular species in serum was performed by a lipidomics strategy using liquid chromatography coupled to mass spectrometry. Obesity, independent of genetic influences, was primarily related to increases in lysophosphatidylcholines, lipids found in proinflammatory and proatherogenic conditions and to decreases in ether phospholipids, which are known to have antioxidant properties. These lipid changes were associated with insulin resistance, a pathogonomic characteristic of acquired obesity in these young adult twins. Our results show that obesity, already in its early stages and independent of genetic influences, is associated with deleterious alterations in the lipid metabolism known to facilitate atherogenesis, inflammation and insulin resistance.
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High serum triglyceride (TG) levels is an established risk factor for coronary heart disease (CHD). Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation.
Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA). Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher's Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network.
We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG) were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1) reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals.
This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.
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Adolescent alcohol abuse is associated with adverse outcomes in early adulthood, but differences in familial status and structure and household and community environments correlate with both adolescent drinking and adverse adult outcomes and may explain their association. We studied drinking-discordant twin pairs to evaluate such confounds to ask: Will between-family associations replicate in within-family comparisons?
With longitudinal data from >3,000 Finnish twins, we associated drinking problems at age 18½ with 13 outcomes assessed at age 25; included were sustained substance abuse, poor health, physical symptoms, early coital debut, multiple sexual partners, life dissatisfaction, truncated education, and financial problems. We assessed associations among twins as individuals with linear regression adjusted for correlated observations; within-family analyses of discordant twin pairs followed, comparing paired means for adult outcomes among co-twins discordant for adolescent problem drinking. Defining discordance by extreme scores on self-reported problem drinking at age 18½ permitted parallel analyses of twins as individuals and discordant twin pairs. Alternate definitions of pair-wise discordance and difference score correlations across the entire twin sample yielded supplementary analyses.
All individual associations were highly significant for all definitions of discordance we employed. Depending on definitions of discordance, 11 to 13 comparisons of all drinking-discordant twin pairs and 3 to 6 comparisons of discordant monozygotic (MZ) twin pairs replicated between-family associations. For most outcomes, effect size attenuated from individual-level analysis to that within discordant MZ twin pairs providing evidence of partial confounding in associations reported in earlier research. The exception was the General Health Questionnaire (GHQ); at age 25, GHQ-12 had equivalent associations with age 18½ Rutgers Alcohol Problem Index across all comparisons.
Our analyses control for shared family background, and, partly or fully, for shared genes, to yield within-family replications and more compelling evidence than previously available that adolescent alcohol abuse disrupts transitions into early adulthood.
We examined mid-adolescent psychosocial problems as risk factors for subsequent depression up to adulthood proper, and differences in these for episodic and persistent depression.
In a 16-year follow-up of an urban Finnish community cohort (547 males and 714 females) from age 16 years risk factors for subsequent depression (S-BDI) were studied. Data were collected with a classroom questionnaire at 16 years and a postal questionnaire at 22 and 32 years. Differences in predictors for episodic depression (only at age of 22 or 32 y) and persistent depression (both at 22 and 32 y) were studied using logistic and multinomial regression analyses.
Mid-adolescent depressive symptoms predicted persistent and female sex episodic depression. Low self-esteem, dissatisfaction with academic achievement, problems with the law, having no dating experiences, and parental divorce all predicted both episodic and persistent depression.
We had two assessment points in adulthood, but no information about depression between these.
The associations between mid-adolescent psychosocial problems and subsequent depression extended up to adulthood proper, somewhat differently for episodic and persistent depression. Preventive efforts should be focused towards young people at risk.
To examine which socioeconomic, family, personal and lifestyle risk factors in adolescence were the strongest independent predictors of excessive alcohol use in adulthood.
In a prospective longitudinal study, all 16-year-olds of one Finnish city completed questionnaires at school, and were followed up by postal questionnaires at 32 years of age [n = 1,471, (females n = 805, males n = 666); response rate 70.3%). The alcohol use disorders identification test (AUDIT) was used to assess alcohol use in adulthood. AUDIT scores of 8 or more for females and 10 or more for males were classified as excessive alcohol use. Adolescent risk factors examined were parental social class, school performance, depressive symptoms, self-esteem, impulsiveness, parental divorce, relationships with parents, parental trust, health behaviour, leisure-time spent with friends, dating, and problems with the law.
All the socioeconomic, family, personal, and lifestyle variables in adolescence, except parental social class in both genders and self-esteem among females, showed significant univariate associations with excessive alcohol use at age 32 years. Multivariate logistic regression analysis showed that among adolescent males, parental divorce, moderate and high level of depressive symptoms, leisure-time spent daily among friends and moderate and drunkenness-orientated drinking were the strongest predictors of excessive alcohol use in adulthood. Among females, the strongest adolescent predictors of excessive alcohol use in adulthood were drunkenness-orientated drinking and frequent smoking.
Early interventions for adolescent substance use and a set of specific psychosocial risk factors should be tailored and evaluated as methods for identifying those at high risk of and preventing excessive alcohol use in adulthood.
The aim of this study was to examine the effects of genetic and environment influences and sex on injury involvement using two sets of Finnish twin data. The younger participants were 955 twins born between 1983 and 1987, aged 20 to 24 years. The older participants were 12,428 twins born between 1930 and 1957, aged 33 to 60 years. Within-twin correlations in monozygotic and dizygotic twins suggested that genetic effects play no role in injury involvement among young twins, but do have some effect at older ages. The results indicated that environmental factors have greater importance in injury involvement than genetic factors in the younger twin data set (FT12), whereas in a middle-aged (33-60 years) twin data set, genetic effects explained about quarter of the variance in injury involvement. Sex was a strong contributing factor, with males being generally more prone to injuries than females.
The aim of this study was to investigate alcohol consumption in relation to the incidence of type 2 diabetes.
The study population consisted of 22778 twins of the Finnish Twin Cohort. This cohort was compiled in 1975 and includes all same-sexed twins born in Finland before 1958. Information on alcohol, smoking, diet, physical activity, medical, and social conditions was obtained by questionnaires administered in 1975, 1981, and 1990. By record linkage to national registers of hospital discharge and prescribed medication, 580 incident cases of type 2 diabetes were identified during 20 years of follow-up.
Moderate alcohol consumption (5-29.9 g/day in men and 5-19.9 g/day in women) tended to be associated with a reduced incidence of type 2 diabetes compared with low consumption (or=25.0 kg/m(2)) subjects (relative risk 0.7, 95% CI 0.5-1.0 [men]; 0.6, 0.3-1.1 [women]). High alcohol consumption (>or=20 g/day) was associated with an increased incidence of type 2 diabetes in lean women (2.9, 1.1-7.5) but not in overweight women or in men. In women, binge drinking was associated with an increased incidence of type 2 diabetes (2.1, 1.0-4.4). Analyses of alcohol-discordant twin pairs supported a reduced risk in moderate consuming twins compared with their low-consuming cotwins (odds ratio 0.5, 95% CI 0.2-1.5).
The results of this study suggested that moderate alcohol consumption may reduce the risk of type 2 diabetes. On the other hand, binge drinking and high alcohol consumption may increase the risk of type 2 diabetes in women.
To investigate life expectancy and mortality among former elite athletes and controls.
HR analysis of cause-specific deaths sourced from the national death registry for former Finnish male endurance, team and power sports athletes (N=2363) and controls (N=1657). The median follow-up time was 50 years.
Median life expectancy was higher in the endurance (79.1 years, 95% CI 76.6 to 80.6) and team (78.8, 78.1 to 79.8) sports athletes than in controls (72.9, 71.8 to 74.3). Compared to controls, risk for total mortality adjusted for socioeconomic status and birth cohort was lower in the endurance ((HR 0.70, 95% CI 0.61 to 0.79)) and team (0.80, 0.72 to 0.89) sports athletes, and slightly lower in the power sports athletes (0.93, 0.85 to 1.03). HR for ischaemic heart disease mortality was lower in the endurance (0.68, 0.54 to 0.86) and team sports (0.73, 0.60 to 0.89) athletes. HR for stroke mortality was 0.52 (0.33 to 0.83) in the endurance and 0.59 (0.40 to 0.88) in the team sports athletes. Compared to controls, the risk for smoking-related cancer mortality was lower in the endurance (HR 0.20, 0.08 to 0.47) and power sports (0.40, 0.25 to 0.66) athletes. For dementia mortality, the power sports athletes, particularly boxers, had increased risk (HR 4.20, 2.30 to 7.81).
Elite athletes have 5-6 years additional life expectancy when compared to men who were healthy as young adults. Lower mortality for cardiovascular disease was in part due to lower rates of smoking, as tobacco-related cancer mortality was especially low.
The authors tested the hypothesis that either prenatal feminization or masculinization hormone influences in utero or later socialization affects the risk for anorexia and bulimia nervosa and disordered eating in members of opposite-sex twin pairs.
Finnish twins (N=2,426 women, N=1,962 men with known zygosity) from birth cohorts born 1974-1979 were assessed at age 22 to 28 years with a questionnaire for eating disorder symptoms. Based on the questionnaire screen, women (N=292), men (N=53), and their cotwins were interviewed to assess diagnoses of anorexia nervosa and bulimia nervosa (per DSM-IV and broad criteria).
In women from opposite-sex twin pairs, the prevalence of DSM-IV or broad anorexia nervosa was not significantly different than that of women from monozygotic pairs or same-sex dizygotic pairs. Of the five male anorexia nervosa probands, only one was from an opposite-sex twin pair. Bulimia nervosa in men was too rare to be assessed by zygosity; the prevalence of DSM-IV or broad bulimia nervosa did not differ in women from opposite- versus same-sex twin pairs. In both sexes, the overall profile of indicators on eating disorders was rather similar between individuals from opposite- and same-sex pairs.
The authors found little evidence that the risk for anorexia nervosa, bulimia nervosa, or disordered eating was associated with zygosity or sex composition of twin pairs, thus making it unlikely that in utero femininization or masculinization or socialization effects of growing up with an opposite-sex twin have a major influence on the later development of eating disorders.
The mechanisms through which genes influence body weight are not well understood, but appetite has been implicated as one mediating pathway. Here we use data from two independent population-based Finnish cohorts (4632 adults aged 25-74 years from the DILGOM study and 1231 twin individuals aged 21-26 years from the FinnTwin12 study) to investigate whether two appetitive traits mediate the associations between known obesity-related genetic variants and adiposity. The results from structural equation modelling indicate that the effects of a polygenic risk score (90 obesity-related loci) on measured body mass index and waist circumference are partly mediated through higher levels of uncontrolled eating (ßindirect = 0.030-0.032, P
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