1. Dmo1 (Diabetes Mellitus OLETF type I) is a major quantitative trait locus for dyslipidaemia, obesity and diabetes phenotypes of male Otsuka Long Evans Tokushima Fatty (OLETF) rats. 2. Our congenic lines, produced by transferring Dmo1 chromosomal segments from the non-diabetic Brown Norway (BN) rat into the OLETF strain, have confirmed the strong, wide-range therapeutic effects of Dmo1 on dyslipidaemia, obesity and diabetes in the fourth (BC4) and fifth (BC5) generations of congenic animals. Analysis of a relatively small number of BC5 rats (n = 71) suggested that the critical Dmo1 interval lies within a
Overweight and obesity in mid- and late-life may increase risk for dementia, whereas a decline in body weight or body mass index (BMI) and underweight in years preceding a clinical dementia diagnosis are also associated with dementia. Little is known about the modifying effect of the APOE genotype, a major susceptibility gene for Alzheimer's disease (AD), on the BMI-dementia adult life course trajectory.
We evaluated the exposure, BMI, in relationship to the outcome, clinical dementia, over 37 years, considering the effect modification of the APOE ?4 allele.
The Prospective Population Study of Women (PPSW) in Sweden is a systematic sample of 1462 women born 1908, 1914, 1918, 1922, and 1930 and aged 38-60 years at baseline. Examinations occurred in 1968, 1974, 1980, 1992, 2000, and 2005; 559 women had information on dementia, BMI, and APOE ?4 allele status, in addition to covariates. Statistical analyses were conducted using mixed effects regression models.
Trajectories of BMI over 37 years differed by APOE ?4 allele status. While women gained BMI similarly from mid-life to age 70 years, women with at least one APOE ?4 allele experienced BMI decline more quickly after age 70 years compared to women without an APOE ?4 allele. However, upon stratifying the sample by dementia occurrence, it appeared that dementia drove the overall BMI-trajectory. There was a main effect of age, interactions of age by APOE ?4 allele status, and age by presence versus absence of dementia.
Women with similar average BMI at mid-life exhibited different BMI trajectories in relation to dementia occurrence. In addition, the pattern of BMI decline in late-life differed on the basis of APOE ?4 allele possession. Thus, these data suggest roles for both dementia- and APOE-associated changes in BMI during the adult life course.
BACKGROUND: Adult body mass index (BMI weight (kg)/height2 (m2)) usually shows familial correlations below 0.3, which are almost entirely due to genetic influences. The considerable remaining non-familial individual variation may be due to non-shared environmental influences which, however, may interact with or modify the genetic influence. OBJECTIVE: To investigate whether the genetic influence on adult BMI is modified by various obesity-related environmental conditions during childhood and adulthood. DESIGN: Adoption study, in which the genetic influence is assessed by the correlations in adult BMI between adoptees and their biological fathers, mothers and full siblings. These correlations were compared between groups of families characterized by differences in rearing or adult environment of the adoptees and/or their biological relatives. SUBJECTS: Height, current weight and greatest weight ever, were obtained in 3651 subjects, who were adopted by non-related families in Copenhagen between 1924 and 1947. Groups representing thin, medium weight, overweight and obese proband adoptees were selected by current BMI (n = 540) and by maximum BMI (n = 524). The members of the biological and adoptive families of the proband adoptees were identified and their BMI was computed from height and weight obtained by mailed questionnaires. MAIN VARIABLES: Indicators related to the rearing environment of the adoptees were age of the adoptee at transfer to the adoptive family, region of residence, presence of adoptive siblings and, for the adoptive parents, year of birth, age at time of adoption, occupational rating, smoking habits and BMI. Indicators of the environment of both the adoptee and the biological relatives were: year of birth; occupational rating and smoking habits, and, of the environment of the biological parents, age and parity at birth of the adoptee. RESULTS: The correlations in BMI between adoptees and the biological fathers, mothers and siblings were 0.11, 0.15 and 0.26 for adoptees selected by current BMI, and 0.13, 0.16, and 0.27 for adoptees selected by maximum BMI, respectively (all P
Associations between a 45 bp 3'untranslated insertion polymorphism in the uncoupling protein 2 (UCP2) gene and both body mass index (BMI) and sleeping metabolic rate have previously been reported. We investigated the impact of this polymorphism on BMI and long-term body weight changes.
The allelic frequency of the UCP2 insertion variant was determined in a cohort of 744 obese Danish Caucasian men who had a BMI of at least 31 kg/m2 at the draft-board examinations and a randomly selected control cohort consisting of 872 draftees. Follow-up measurements of BMI were done on average 26 years after the draft-board examinations.
The prevalence of the insertion allele was 30.4% (95% confidence interval: 28.0-32.8%) among the obese and 29.6% (27.4-31.8%) in the control group (p = 0.6). In a lean group selected as the 354 subjects with a BMI less than 25 kg/m2 at 46 years of age from the control group, the frequency of insertion allele was 29.0% (27.2-30.8%) (p = 0.5 compared with the obese cohort). The BMI at the ages of 20 and 46 years did not differ between genotypes either in the obese or the control group. Similarly, the changes in BMI/year between examinations at 20 and 46 years of age did not differ between genotypes in either group.
In a large group of Danish Caucasian men we found no association between a 3'untranslated insertion polymorphism in the UCP2 gene and obesity. Neither did we identify a relation between this variant and BMI changes during adult age.
BACKGROUND: Assessment of eating disorders at the symptom level can facilitate the refinement of phenotypes. We examined genetic and environmental contributions to liability to anorexia nervosa (AN) symptoms in a population-based twin sample using a genetic common pathway model. METHOD: Participants were from the Norwegian Institute of Public Health Twin Panel (NIPHTP) and included all female monozygotic (MZ; 448 complete pairs and four singletons) and dizygotic (DZ; 263 complete pairs and four singletons) twins who completed the Composite International Diagnostic Interview (CIDI) assessing DSM-IV Axis I and ICD-10 criteria. Responses to items assessing AN symptoms were included in a model fitted using the marginal maximum likelihood (MML) approach. RESULTS: Heritability of the overall AN diagnosis was moderate [a2=0.22, 95% confidence interval (CI) 0.0-0.50] whereas heritabilities of the specific items varied. Heritability estimates for weight loss items were moderate (a2=0.31-0.34) and items assessing weight concern when at a low weight were smaller (0.18-0.29). Additive genetic factors contributed little to the variance of amenorrhea, which was most strongly influenced by unshared environment (a2=0.16, e2=0.71). CONCLUSIONS: AN symptoms are differentially heritable. Specific criteria such as those related to body weight and weight loss history represent more biologically driven potential endophenotypes or liability indices. The results regarding weight concern differ somewhat from those of previous studies, highlighting the importance of assessing genetic and environmental influences on variance of traits within specific subgroups of interest.
Adiponectin, secreted mainly by mature adipocytes, is a protein with insulin-sensitising and anti-atherogenic effects. Human adiponectin is encoded by the ADIPOQ gene on the chromosomal locus 3q27. Variations in ADIPOQ are associated with obesity, type 2 diabetes (T2DM) and related phenotypes in several populations. Our aim was to study the association of the ADIPOQ variations with body weight, serum adiponectin concentrations and conversion to T2DM in overweight subjects with impaired glucose tolerance. Moreover, we investigated whether ADIPOQ gene variants modify the effect of lifestyle changes on these traits.
Participants in the Finnish Diabetes Prevention Study were randomly assigned to a lifestyle intervention group or a control group. Those whose DNA was available (n = 507) were genotyped for ten ADIPOQ single nucleotide polymorphisms (SNPs). Associations between SNPs and baseline body weight and serum adiponectin concentrations were analysed using the univariate analysis of variance. The 4-year longitudinal weight data were analysed using linear mixed models analysis and the change in serum adiponectin from baseline to year four was analysed using Kruskal-Wallis test. In addition, the association of SNPs with the risk of developing T2DM during the follow-up of 0-11 (mean 6.34) years was analysed by Cox regression analysis.
rs266729, rs16861205, rs1501299, rs3821799 and rs6773957 associated significantly (p
Cites: Circulation. 1999 Dec 21-28;100(25):2473-610604883
The association of the Pro12Ala polymorphism of the PPAR-gamma2 gene with the incidence of type 2 diabetes was investigated in 522 subjects with impaired glucose tolerance (IGT) participating in the Finnish Diabetes Prevention Study. Subjects were randomized to either an intensive diet and exercise group or a control group. By 3 years of intervention, the odds ratio of the development of type 2 diabetes for subjects with the Ala12 allele was 2.11-fold compared with that for subjects with the Pro12Pro genotype (95% CI 1.20-3.72). The risk for type 2 diabetes increased also in subjects who gained weight or belonged to the control group. In the intervention group, subjects with the Ala12Ala genotype lost more weight during the follow-up than subjects with other genotypes (Pro12Pro vs. Ala12Ala P = 0.043), and none of subjects with the Ala12Ala genotype developed type 2 diabetes in this group. In conclusion, the Ala12 allele may predispose to the development of type 2 diabetes in obese subjects with IGT. However, beneficial changes in diet, increases in physical activity, and weight loss may reverse, to some extent, the diabetogenic impact of the Ala12 allele, possibly due to an improved insulin sensitivity.
Assortative mating by body height and weight is well established in various populations, but its causal mechanisms remain poorly understood. We analyzed the effect of phenotypic assortment and social homogamy on spousal correlations for body height and body mass index (BMI, kg/m(2)). Our data derived from a questionnaire administered to the adult Finnish Twin Cohort in 1990 (response rate 77%) yielding results from 922 monozygotic and 1697 dizygotic adult twin pairs who reported information about their body height and weight and that of their spouses. Assortative mating was evident for body height and BMI. For body height, the effects of social homogamy (0.24 in men and 0.29 in women) and phenotypic assortment (0.27 and 0.28, respectively) were about the same. For BMI, the effect of social homogamy was stronger (0.31 in men and 0.28 in women) than the effect of phenotypic assortment (0.13 in both men and women). When assortative mating was taken into account, shared environmental factors had no effect on phenotypic variation in body height or BMI. Our results show that assortative mating needs to be considered in population genetic studies of body height and weight.
This study evaluated intraindividual child-adult and interindividual child-parent relationships of body mass index (BMI) using data from the Trois-RiviÃ¨res semilongitudinal study of growth and development. Intraindividual correlations between age 12 and 35 years were substantial (r(2) = 36% of variance in women, 30% of variance in men). Interindividual child-parent correlations for mothers and fathers age 36.6 +/- 0.4 and 39.5 +/- 0.4 years, respectively, were very low to low for daughters age 12 years (r = 0.09, NS and 0.34, P
The causal role of obesity in the development of depression remains uncertain. We applied instrumental-variables regression (Mendelian randomization) to examine the association of adolescent and adult body mass index (BMI) with adult depressive symptoms. Participants were from the Young Finns prospective cohort study (n?=?1731 persons, 2844 person-observations), with repeated measurements of BMI and depressive symptoms (modified Beck's Depression Inventory). Genetic risk score of 31 single nucleotide polymorphisms previously identified as robust genetic markers of body weight was used as a proxy for variation in BMI. In standard linear regression analysis, higher adult depressive symptoms were predicted by higher adolescent BMI (B?=?0.33, CI?=?0.06-0.60, P?=?0.017) and adult BMI (B?=?0.47, CI?=?0.32-0.63, P?