Strong Evidence for a Genetic Contribution to Late-Onset Alzheimer’s Disease Mortality: A Population-Based Study

Background

Alzheimer’s disease (AD) is an international health concern that has a devastating effect on patients and families. While several genetic risk factors for AD have been identified much of the genetic variance in AD remains unexplained. There are limited published assessments of the familiality of Alzheimer’s disease. Here we present the largest genealogy-based analysis of AD to date.

Methods

We assessed the familiality of AD in The Utah Population Database (UPDB), a population-based resource linking electronic health data repositories for the state with the computerized genealogy of the Utah settlers and their descendants. We searched UPDB for significant familial clustering of AD to evaluate the genetic contribution to disease. We compared the Genealogical Index of Familiality (GIF) between AD individuals and randomly selected controls and estimated the Relative Risk (RR) for a range of family relationships. Finally, we identified pedigrees with a significant excess of AD deaths.

Results

The GIF analysis showed that pairs of individuals dying from AD were significantly more related than expected. This excess of relatedness was observed for both close and distant relationships. RRs for death from AD among relatives of individuals dying from AD were significantly increased for both close and more distant relatives. Multiple pedigrees had a significant excess of AD deaths.

Conclusions

These data strongly support a genetic contribution to the observed clustering of individuals dying from AD. This report is the first large population-based assessment of the familiality of AD mortality and provides the only reported estimates of relative risk of AD mortality in extended relatives to date. The high-risk pedigrees identified show a true excess of AD mortality (not just multiple cases) and are greater in depth and width than published AD pedigrees. The presence of these high-risk pedigrees strongly supports the possibility of rare predisposition variants not yet identified.     

Risk Factors for Adult Overweight and Obesity in the Quebec Family Study: Have We Been Barking Up the Wrong Tree?

The aim of this study was to determine the independent contribution of previously reported risk factors for adult overweight and obesity. A cross‐sectional (n = 537) and a longitudinal (n = 283; 6‐year follow‐up period) analysis was performed for nine risk factors for overweight and obesity assessed in adult participants (aged 18–64 years) of the Quebec Family Study (QFS). The main outcome measure was overweight/obesity, defined as a BMI ≥25 kg/m². Using logistic regression analysis adjusted for age, sex, and socioeconomic status, short sleep duration, high disinhibition eating behavior, low dietary calcium intake, high susceptibility to hunger behavior, nonparticipation in high‐intensity physical exercise, high dietary restraint behavior, nonconsumption of multivitamin and dietary supplements, high dietary lipid intake, and high alcohol intake were all significantly associated with overweight and obesity in the cross‐sectional sample. The analysis of covariance adjusted for age, socioeconomic status, and all other risk factors revealed that only individuals characterized by short sleep duration, high disinhibition eating behavior, and low dietary calcium intake had significantly higher BMI compared to the reference category in both sexes. Over the 6‐year follow‐up period, short‐duration sleepers, low calcium consumers, and those with a high disinhibition and restraint eating behavior score were significantly more likely to gain weight and develop obesity. These results show that excess body weight or weight gain results from a number of obesogenic behaviors that have received considerable attention over the past decade. They also indicate that the four factors, which have the best predictive potential of variations in BMI, be it in a cross‐sectional or a longitudinal analytical design, do not have a “caloric value” per se.     

Genetic Variability of Adult Body Mass Index: A Longitudinal Assessment in Framingham Families

Objective: To explore the contribution of genetics to the mean, SD, maximum value, maximum less the mean, and change over time in body mass index (BMI) and the residual of body weight after adjustment for height. BMI is frequently used as a general indicator of obesity because of its ease and reliability in ascertainment. Cross‐sectional twin and family studies have shown a moderate‐to‐substantial genetic component for BMI. However, the contribution of genetics to the long‐term average, variability, or change over time in BMI is less clear. Research Methods and Procedures: Longitudinal data from the Framingham heart study were used to create pedigrees of age‐matched individuals. Heritability estimates were derived using variance‐decomposition methods on a total of 1051 individuals from 380 extended pedigrees followed for a period of 20 years. All subjects were followed from approximately age 35 to 55 years. Results: Moderate heritability estimates were found for the mean BMI (h² = 0.37), maximum BMI (h² = 0.40), and the mean residual of body weight (h² = 0.36). Low heritability estimates (h² ? 0.20) were found for the maximum less the mean in BMI and the SDs of BMI and residual of body weight. No additive genetic contribution was found for the average change over time in BMI or the residual of body weight. Discussion: These findings suggest that there is a significant genetic component for the magnitude of BMI throughout an individual's middle‐adult years; however, little evidence was found for a genetic contribution to the variability or rate of change in an individual's BMI.     

Excess Weight and the Risk of Incident Coronary Heart Disease Among Men and Women

Overweight and obesity have been prospectively associated with the risk of coronary heart disease (CHD). Less clear is the relation of excess weight to risk of CHD among men and women with comorbid conditions, and the proportion of CHD risk attributable to excess weight in the US population. To assess the risk of CHD associated with excess weight among men and women with and without associated comorbid conditions, and determine the population attributable risk of CHD associated with excess weight. The study population consisted of two prospective cohorts, the Health Professionals Follow‐up Study (HPFS) (N = 42,351 men; age range at baseline, 39–75 years) and the Nurses' Health Study (NHS) (N = 76,703 women; age range at baseline, 39–65 years). A total of 2,771 incident cases of CHD among the men and 2,359 among the women were documented over the 16 years of follow‐up. Overall, the relative risk (RR) of CHD associated with BMI ≥30 kg/m² compared with BMI 18.5–22.9 kg/m² was 2.13 (95% confidence interval (CI), 1.82–2.48) among the men and 2.48 (95% CI, 2.20–2.80) among the women. The risk of CHD increased with BMI, both with and without the presence of comorbid conditions. Our estimates suggest that more than a third of all incident CHD in US men and women may be attributed to excess weight. Excess weight is associated with increased risk of CHD among men and women, both alone and in combination with comorbid conditions, though the results require careful interpretation. A substantial proportion of incident CHD may be attributed to excess weight.     

Identification of an Obese Eating Style in 4‐year‐old Children Born at High and Low Risk for Obesity

This study tested whether children's eating behavior and parental feeding prompts during a laboratory test meal differ among children born at high risk (HR) or low risk (LR) for obesity and are associated with excess child weight gain. At 4 years of age, 32 HR children (mean maternal prepregnancy BMI = 30.4 kg/m²) and 29 LR children (maternal BMI = 19.6 kg/m²) consumed a test meal in which their eating behavior was assessed, including rate of caloric consumption, mouthfuls/min, and requests for food. Parental prompts for the child to eat also were measured at year 4, and child body composition was measured at ages 4 and 6 years. T‐tests, and logistic and multiple regression analyses tested study aims. Results indicated that HR and LR children did not differ in eating rate or parental feeding prompts. Greater maternal BMI, child mouthfuls of food/min, and total caloric intake/min during the test meal predicted an increased risk of being overweight or obese at age 6, whereas greater active mealtime was associated with a reduced risk of being overweight or obese. Regression analyses indicated that only mouthfuls of food/min predicted changes in BMI from 4 to 6 years, and mouthfuls of food/min and gender predicted 2‐year changes in sum of skinfolds and total body fat. Thus, a rapid eating style, characterized by increased mouthfuls of food/min, may be a behavioral marker for the development of childhood obesity.     

A new body shape index predicts mortality hazard independently of body mass index

Background

Obesity, typically quantified in terms of Body Mass Index (BMI) exceeding threshold values, is considered a leading cause of premature death worldwide. For given body size (BMI), it is recognized that risk is also affected by body shape, particularly as a marker of abdominal fat deposits. Waist circumference (WC) is used as a risk indicator supplementary to BMI, but the high correlation of WC with BMI makes it hard to isolate the added value of WC.

Methods and Findings

We considered a USA population sample of 14,105 non-pregnant adults () from the National Health and Nutrition Examination Survey (NHANES) 1999–2004 with follow-up for mortality averaging 5 yr (828 deaths). We developed A Body Shape Index (ABSI) based on WC adjusted for height and weight: ABSI had little correlation with height, weight, or BMI. Death rates increased approximately exponentially with above average baseline ABSI (overall regression coefficient of per standard deviation of ABSI [95% confidence interval: –]), whereas elevated death rates were found for both high and low values of BMI and WC. (–) of the population mortality hazard was attributable to high ABSI, compared to (–) for BMI and (–) for WC. The association of death rate with ABSI held even when adjusted for other known risk factors including smoking, diabetes, blood pressure, and serum cholesterol. ABSI correlation with mortality hazard held across the range of age, sex, and BMI, and for both white and black ethnicities (but not for Mexican ethnicity), and was not weakened by excluding deaths from the first 3 yr of follow-up.

Conclusions

Body shape, as measured by ABSI, appears to be a substantial risk factor for premature mortality in the general population derivable from basic clinical measurements. ABSI expresses the excess risk from high WC in a convenient form that is complementary to BMI and to other known risk factors.     

Effects of Heritability,Shared Environment,and Nonshared Intrauterine Conditions on Child and Adolescent BMI

Heritability studies of BMI, based upon twin samples, have identified genetic and shared environmental components of BMI, but have been largely silent about the nonshared environmental factors. Intrauterine factors have been identified as having significant long‐term effects on BMI and may be a critical source of nonshared environmental influence. Extant studies based on samples of either unrelated individuals or twins cannot separate the effects of genetics, shared environments, and nonshared intrauterine conditions because the one lacks variation in the degree of relatedness and the other has insufficient variation in intrauterine conditions. This study improves upon these prior studies by using a large, sibling‐based sample to examine heritability, shared environmental, and nonshared intrauterine influences on BMI during two age periods in childhood (6–8 years; 12–14 years). The primary interest was in determining the effects of the intrauterine environment on BMI as a component of the nonshared environment and in determining whether there were sex‐specific differences in heritability and/or in the intrauterine factors. These were estimated using regression‐based techniques introduced by DeFries and Fulker. Heritability of BMI was estimated to be 0.20–0.28 at 6–8 years and 0.46–0.61 at 12–14 years. Differences in heritability were found at 12–14 years between same‐sex as compared to mixed‐sex pairs. The shared environmental effect was significant at 6–8 years but insignificant at 12–14 years. Differences in birth weight were significant in all groups at 6–8 years suggesting long‐term effects of the nonshared intrauterine environment; at 12–14 years, birth weight was no longer significant for girls.     

Maternal eNOS deficiency determines a fatty liver phenotype of the offspring in a sex dependent manner

Maternal environmental factors can impact on the phenotype of the offspring via the induction of epigenetic adaptive mechanisms. The advanced fetal programming hypothesis proposes that maternal genetic variants may influence the offspring's phenotype indirectly via epigenetic modification, despite the absence of a primary genetic defect. To test this hypothesis, heterozygous female eNOS knockout mice and wild type mice were bred with male wild type mice. We then assessed the impact of maternal eNOS deficiency on the liver phenotype of wild type offspring. Birth weight of male wild type offspring born to female heterozygous eNOS knockout mice was reduced compared to offspring of wild type mice. Moreover, the offspring displayed a sex specific liver phenotype, with an increased liver weight, due to steatosis. This was accompanied by sex specific differences in expression and DNA methylation of distinct genes. Liver global DNA methylation was significantly enhanced in both male and female offspring. Also, hepatic parameters of carbohydrate metabolism were reduced in male and female offspring. In addition, male mice displayed reductions in various amino acids in the liver. Maternal genetic alterations, such as partial deletion of the eNOS gene, can affect liver metabolism of wild type offspring without transmission of the intrinsic defect. This occurs in a sex specific way, with more detrimental effects in females. This finding demonstrates that a maternal genetic defect can epigenetically alter the phenotype of the offspring, without inheritance of the defect itself. Importantly, these acquired epigenetic phenotypic changes can persist into adulthood.     

Waist circumference correlates with metabolic syndrome indicators better than percentage fat

Objective : Percent fat is often considered the reference for establishing the magnitude of adipose tissue accumulation and the risk of excess adiposity. However, the increasing recognition of a strong link between central adiposity and metabolic disturbances led us to test whether waist circumference (WC) is more highly correlated with metabolic syndrome components than percent fat and other related anthropometric measures such as BMI. Research Methods and Procedures : BMI, WC, and percent fat, measured by DXA, were evaluated in 1010 healthy white and African‐American men and women [age, 48.3 ± 17.2 (standard deviation) years; BMI, 27.0 ± 5.3 kg/m²]. The associations of BMI, WC, and percent fat with age and laboratory‐adjusted health risk indicators (i.e., serum glucose, insulin, triglycerides, high‐density lipoprotein cholesterol, blood pressure) in each sex and ethnicity group were examined. Results : For 18 of 24 comparisons, the age‐ and laboratory‐adjusted correlations were lowest for percent fat and in 16 of 24 comparisons were highest for WC. Fifteen of the between‐method differences reached statistical significance. With health risk indicator as the dependent variable and anthropometric measures as the independent variable, the contribution of percent fat to the WC regression model was not statistically significant; in contrast, adding WC to the percent fat regression model did make a significant independent contribution for most health risk indicators. Discussion : WC had the strongest associations with health risk indicators, followed by BMI. Although percent fat is a useful measure of overall adiposity, health risks are best represented by the simply measured WC.     

A pediatric weight management program for high-risk populations: a preliminary analysis

Objective: To determine whether a multidisciplinary pediatric weight management program effectively improves BMI, BMI z‐score, and cardiovascular risk factors (CVRFs) in high‐risk populations. Methods and Procedures: A retrospective chart review was performed on children seen in the NEW Kids Program at the Children's Hospital of Wisconsin, a family‐based clinic that treats pediatric obesity using medical management, nutrition education, behavioral intervention, and physical activity. Inclusion criteria were program participation for ≥9 months and >4 visits. Analyses were performed to identify factors associated with pre‐ to postintervention changes in BMI, BMI z‐score, and CVRF laboratory values. Results: A total of 66 patients met inclusion criteria; the mean age was 11 years (s.d. ± 3.4), 56% were racial/ethnic minorities, 45% were Medicaid recipients, 48% resided in impoverished communities, and 38% had a BMI ≥40 kg/m². Of the 66 patients, 91% had more than one weight‐related comorbidity, 88% had CVRFs, and the preintervention mean BMI was 37 kg/m². After the intervention, there was an overall increase in absolute BMI, but a small, yet significant decrease in BMI z‐score (mean ?0.03 ± 0.16; P < 0.05). There were significant pregroup to postgroup improvements in total cholesterol, low‐density lipoprotein, and triglycerides levels (P < 0.05). Insurance coverage, race/ethnicity, gender, age, and initial BMI were not significantly associated with changes in BMI or BMI z‐score. Discussion: A multidisciplinary pediatric weight management program can improve the weight status of high‐risk populations, including minorities, Medicaid recipients, patients with multiple comorbidities and CVRFs, and the severely obese.     

Linkage and Genome‐wide Association Analysis of Obesity‐related Phenotypes: Association of Weight With the MGAT1 Gene

As major risk‐factors for diabetes and cardiovascular diseases, the genetic contribution to obesity‐related traits has been of interest for decades. Recently, a limited number of common genetic variants, which have replicated in different populations, have been identified. One approach to increase the statistical power in genetic mapping studies is to focus on populations with increased levels of linkage disequilibrium (LD) and reduced genetic diversity. We have performed joint linkage and genome‐wide association analyses for weight and BMI in 3,448 (linkage) and 3,925 (association) partly overlapping healthy individuals from five European populations. A total of four chromosomal regions (two for weight and two for BMI) showed suggestive linkage (lod >2.69) either in one of the populations or in the joint data. At the genome‐wide level (nominal P < 1.6 × 10^?7, Bonferroni‐adjusted P < 0.05) one single‐nucleotide polymorphism (SNP) (rs12517906) (nominal P = 7.3 × 10^?8) was associated with weight, whereas none with BMI. The SNP associated with weight is located close to MGAT1. The monoacylglycerol acyltransferase (MGAT) enzyme family is known to be involved in dietary fat absorption. There was no overlap between the linkage regions and the associated SNPs. Our results show that genetic effects influencing weight and BMI are shared across diverse European populations, even though some of these populations have experienced recent population bottlenecks and/or been affected by genetic drift. The analysis enabled us to identify a new candidate gene, MGAT1, associated with weight in women.     

The extended relationship between child cardiovascular risks and academic performance measures

Objective: To examine the relationship between children's overweight status and other cardiovascular risk fitness factors and academic performance among fifth‐grade students. Research Methods and Procedures: Using a sample of 968 fifth‐grade students (50.7% boys; mean age = 10.6 years), children's cardiovascular risks (BMI, blood pressure, acanthosis nigricans) and fitness measures were compared with their mean group performance scores across four subscales (mathematics, reading/language arts, science, and social studies) of a statewide standardized academic performance test. Results: Of this sample, 39% were either at risk for being overweight or were already overweight; slightly over one half were of normal weight. Initial findings revealed a significant relationship between children's weight category and their reading/language arts, mathematics, and science test scores even after controlling for a proxy of socioeconomic status. When additional cardiovascular risk and fitness measures were included in the model, however, children's BMI status had no association. Instead, a composite fitness index, children's blood pressure, sex, and proxy of socioeconomic status were significantly associated with children's academic test scores. Discussion: This study expanded our understanding of the connection between children's overweight risks and academic performance by examining the impact of other cardiovascular risk factors such as high blood pressure and measures of fitness. These findings support the development and implementation of childhood cardiovascular risk surveillance programs that evaluate not only children's overweight risks but also their fitness, risk for type 2 diabetes, and/or high blood pressure by showing a relationship between some of these risks and children's academic test performance.     

Breast cancer risk and the interaction between adolescent body size and weight gain in later life: A case-control study

BackgroundWhile the breast cancer risk associated with increasing adult BMI in postmenopausal women can be explained by increases in concentrations of endogenous estrogens the biologic mechanisms behind the inverse association between adolescent BMI and breast cancer risk are still a subject of controversial debate.MethodsWe investigated the association of breast cancer with body size and changes in body size across life time estimated by age-specific BMI Z scores and changes in BMI Z scores from teenage years to middle age in an age-matched population-based case-control study of 2994 Australian women. Logistic regression adjusted for the matching factor age and further potential confounders was used.ResultsAdolescent body leanness in postmenopausal women and excess adult weight gain in all study participants were associated with an increased breast cancer risk with an odds ratio [95% confidence interval] of 1.29 [1.08,1.54] and 1.31 [1.09,1.59], respectively. Interaction analyses restricted to postmenopausal women revealed an increased risk of breast cancer in those who were lean during adolescence and gained excess weight during adulthood (odds ratio [95% confidence interval]: 1.52 [1.19,1.95]) but not in women who were lean during adolescence and did not gain excess weight during adulthood (1.20 [0.97,1.48]) and not in women who were not lean during adolescence and but gained excess weight during adulthood (1.10 [0.95,1.27]) compared to postmenopausal women who were neither lean during adolescence nor gained excess weight.ConclusionIn postmenopausal women adolescent leanness was only associated with increased breast cancer risk when excess weight was gained during adulthood.     

Childhood Obesity: Do Parents Recognize This Health Risk?

Objective: This study examined parents’ understanding of excess weight as a health risk, knowledge of healthy eating habits, and recognition of obesity in their children. Research Methods and Procedures: An anonymous questionnaire was distributed during well‐care visits involving children 4 to 8 years of age at a pediatric faculty practice. Parents indicated their level of concern about excess weight and other familiar health risks using a four‐point Likert scale, answered multiple‐choice questions concerning healthy eating patterns, and communicated their perceptions about their child's weight using a visual analog scale. A parent's perception was considered “accurate” if it deviated from the child's growth chart percentile by <30 points. Results: Of the 83 parents surveyed, 23% (19/83) had overweight children (≥95th percentile of age‐ and gender‐specific BMI growth charts). These parents did not differ from other parents in their level of concern about excess weight as a health risk or in their knowledge of healthy eating patterns, but the two groups of parents did differ in the accuracy of their perceptions about their children's weight. Only 10.5% of parents of overweight children (2/19) perceived their child's weight accurately compared with 59.4% of other parents (38/64; p < 0.001). Parents of overweight children invariably underestimated their children's weight. The median difference between their perception and the growth chart percentile was ?45 points. Discussion: Given that most parents of overweight children fail to recognize that their child has a weight problem, pediatricians should develop strategies to help these parents correct their misperceptions.     

Genetic studies on a tumor growth-inhibitory factor in serum of normal mice and its relationship to NK activity

It has been shown that normal mouse serum contains a tumor growth-inhibitory factor (GIF). and that strain-dependent levels of GIF correlate with mouse NK activity. To further analyze the genetic control of GIF we have studied the growth-inhibitory activity of normal mouse serum from 8 different mouse strains and their F1 hybrids. A sensitive method using a chromogenic substrate for an endogenous lysosomal enzyme was used to measure the inhibitory activity of normal mouse serum on the mouse B16 melanoma. The highest level of GIF was found in old mice, lower activity in serum of young animals and no activity in suckling mice. To compare the genetic control of GIF and NK, spleen NK activity against B16 as well as YAC-1 targets was measured in parallel in the same animals. Confirming previous results we found the H-2k strains CBA and C3H to have high levels of GIF as well as NK activity, while the strain A/Sn and the A congenic strain A.SW had low levels of both activities. Experiments with H-2d and H-2b strains, however, showed that GIF and NK had a different genetic control; thus the DBA/2 and Balb/c strains had considerably higher GIF activity than the C57B1 and Leaden strains, while the reverse was true for NK activity. In F1 hybrid crosses between strains with high and low activity, high activity was inherited as a dominant trait for both GIF and NK. A backcross analysis in (A X CBA) X A backcross mice, segregating for NK and GIF showed that the two activities did not cosegregate. These studies therefore demonstrate that GIF and NK activity are under different genetic control, and do not support any direct or simple relationship between GIF and NK cells.     

Contribution of genetics to the concept of risk status for alcohol dependence

The factors involved in the variability of one's own risk for alcohol dependence is multifactorial and mostly unknown. Nevertheless, genetic factors are clearly involved in the risk for the disorder, the impact of addictive genetic factors being evaluated between 30% and 50%. Aggregation studies underline the difficulties of delimiting the boundaries of the phenotype, as some subgroups of alcohol-dependent patients have genetic factors with an increased weight (severe and young-onset disorder, presence of antisocial behavior...). Furthermore, familial studies also showed that the genetic of "addiction" may be more relevant than studying the genetic of one specific dependence. The use of one substance lately abused being probably more dependent of familial and/or environmental features. The discover of susceptibility genes had a greater impact on defining the phenotype than proposing new treatments. Three examples are given in this review. Firstly, le gene coding for the second dopamine receptor may be more specifically involved in severe and comorbid alcohol-dependence. Secondly, the gene coding for the serotonin transporter may increase the suicidal risk in alcohol-dependent patients. Thirdly, the quality of the withdrawal process is partly explained by the existence of a specific genotype of the dopamine transport gene.     

Epidemiology and Genetic Epidemiology of the Liver Function Test Proteins

Background

The liver function test (LFT) is among the most commonly used clinical investigations to assess hepatic function, severity of liver diseases and the effect of therapies, as well as to detect drug-induced liver injury (DILI).

Aims

To determine the relative contribution of genetic and environmental factors as well as test and quantify the effects of sex, age, BMI and alcohol consumption to variation in liver function test proteins - including alanine amino transaminase (ALT), Albumin, gamma glutamyl transpeptidase (GGT), total bilirubin, total protein, total globulin, aspartate transaminase (AST), and alkaline phosphotase (ALP) - using the classical twin model.

Methods

Blood samples were collected from a total of 5380 twin pairs from the TwinsUK registry. We measured the expression levels of major proteins associated with the LFT, calculated BMI from measured weight and height and questionnaires were completed for alcohol consumption by the twins. The relative contribution of genetic and environmental factors to variation in the LFT proteins was assessed and quantified using a variance components model fitting approach.

Results

Our results show that (1) variation in all the LFTs has a significant heritable basis (h² ranging from 20% to 77%); (2) other than GGT, the LFTs are all affected to some extent by common environmental factors (c² ranging from 24% to 54%); and (3) a small but significant proportion of the variation in the LFTs was due to confounding effects of age, sex, BMI, and alcohol use.

Conclusions

Variation in the LFT proteins is under significant genetic and common environmental control although sex, alcohol use, age and BMI also contribute significantly to inter-individual variation in the LFT proteins. Understanding the underlying genetic contribution of liver function tests may help the interpretation of their results and explain wide variation among individuals.     

Genome wide assessment of young onset Parkinson's disease from Finland

In the current study we undertook a series of experiments to test the hypothesis that a monogenic cause of disease may be detectable within a cohort of Finnish young onset Parkinson's disease patients. In the first instance we performed standard genome wide association analyses, and subsequent risk profile analysis. In addition we performed a series of analyses that involved testing measures of global relatedness within the cases compared to controls, searching for excess homozygosity in the cases, and examining the cases for signs of excess local genomic relatedness using a sliding window approach. This work suggested that the previously identified common, low risk alleles, and the risk models associated with these alleles, were generalizable to the Finnish Parkinson's disease population. However, we found no evidence that would suggest a single common high penetrance mutation exists in this cohort of young onset patients.     

Patterns of Objectively Measured Physical Activity in Normal Weight,Overweight, and Obese Individuals (20–85 Years): A Cross-Sectional Study

Background

The magnitude of the association between physical activity (PA) and obesity has been difficult to establish using questionnaires. The aim of the study was to evaluate patterns of PA across BMI-defined weight categories and to examine the independent contribution of PA on weight status, using accelerometers.

Methods

The study was a cross-sectional population-based study of 3,867 adults and older people aged 20–85 years, living in Norway. PA was assessed for seven consecutive days using the ActiGraph GT1M accelerometer. Anthropometrical data was self-reported and overweight and obesity was defined as having a body mass index (BMI) of 25–<30 and ≥30 kg/m², respectively.

Results

Overweight and obese participants performed less overall PA and PA of at least moderate intensity and took fewer steps, compared to normal weight participants. Although overall PA did not differ between weekdays and weekends, an interaction between BMI category and type of day was present, indicating a larger difference in overall PA between BMI categories on weekends compared to weekdays. Obese participants displayed 19% and 25% lower overall physical activity compared to normal weight participants, on weekdays and weekends, respectively. Participants in the most active quintile of overall PA had a 53% lower risk (OR 0.47, 95% CI: 0.37 to 0.60) for having a BMI above or below 25 kg/m², and a 71% lower risk (OR: 0.29, 95% CI: 0.20 to 0.44) for having a BMI above or below 30 kg/m².

Conclusions

Overweight and obese participants engaged in less overall PA and moderate and vigorous PA compared with normal weight individuals. The weight related differences in overall PA were most pronounced on the weekend and the risk of being overweight or obese decreases across quintiles of PA.