Quantitative trait linkage analysis of longitudinal change in body weight

One of the great strengths of the Framingham Heart Study data, provided for the Genetic Analysis Workshop 13, is the long-term survey of phenotypic data. We used this unique data to create new phenotypes representing the pattern of longitudinal change of the provided phenotypes, especially systolic blood pressure and body weight. We performed a linear regression of body weight and systolic blood pressure on age and took the slopes as new phenotypes for quantitative trait linkage analysis using the SOLAR package. There was no evidence for heritability of systolic blood pressure change. Heritability was estimated as 0.15 for adult life "body weight change", measured as the regression slope, and "body weight gain" (including only individuals with a positive regression slope), and as 0.22 for body weight "change up to 50" (regression slope of weight on age up to an age of 50). With multipoint analysis, two regions on the long arm of chromosome 8 showed the highest LOD scores of 1.6 at 152 cM for "body weight change" and of >1.9 around location 102 cM for "body weight gain" and "change up to 50". The latter two LOD scores almost reach the threshold for suggestive linkage. We conclude that the chromosome 8 region may harbor a gene acting on long-term body weight regulation, thereby contributing to the development of the metabolic syndrome.     

The relationship of birth weight with longitudinal changes in body composition in adult women

Most research on birth weight and adult health status has reported adult measures at a single time point. This study examined the relationship of self‐reported birth weight to longitudinal changes in adult body composition in 587 women of the Michigan Bone Health and Metabolism Study, followed from 1992 to 2007 and aged 24–50 years at baseline. Linear mixed models were used to estimate the association between three birth weight categories and women's 15‐year changes in adult weight, height, BMI, waist and hip circumference, waist‐to‐hip ratio, and fat, lean, and skeletal muscle mass. Body composition measures increased in all women over the 15‐year study period. At their adult baseline, high birth weight women weighed 13% more and had waist circumference and lean mass measures that were 5.51 cm and 3.91 kg larger, respectively, than normal birth weight women. No differences were observed in adult body composition between low and normal birth weight women and rates of change in the adult measures did not vary across the birth weight groups. Women heavier at birth continued to be heavier through adulthood, corroborating previous reports based on single measures of adult body composition. Research to address whether higher adult body composition in high birth weight women increases the longitudinal risk for obesity‐related chronic diseases is needed.     

Birth weight and environmental heat load: a between-population analysis

Low birth weight, a major cause of infant morbidity and mortality, is caused by different factors in Western and developing-country populations. In addition to differing in terms of ethnicity, maternal size, maternal nutritional status, and disease load, developing-country and Western populations are also characterized by different environmental heat loads. Thermodynamic theory predicts that heat stress is mitigated by reduced size of both mother and offspring, and therefore generates the hypothesis that reduced birth weight may be an adaptation to environmental heat load. The aim of this study was to test the hypothesis that environmental heat load is associated with between-population variability in birth weight. Data on birth weight and thermal environment were obtained from the literature for 140 populations. Further data on several physical, social, and biological confounders were also collated. After adjusting for confounding factors, of which only maternal height and per capita gross domestic product were statistically significant, heat stress showed a significant inverse relationship with birth weight in 108 populations, accounting for an additional 9.6% of the between-population variance. Though based on data collected from more than one source, these results are consistent with the hypothesis that heat stress is inversely associated with birth weight, as previously reported for within-population studies. Further studies are needed to establish to what extent heat stress is a determinant of low birth weight in developing countries.     

Birth weight correlates differently with cardiovascular risk factors in youth

Objective: Childhood obesity has become prevalent, resulting in a greater risk of hypertension, diabetes, and dyslipidemia. However, the relationship between these comorbid conditions and birth weight remains uncertain. We conducted this study to evaluate the relationship between birth weight and cardiovascular risk factors in children and adolescents. Research Methods and Procedures: In a nationwide survey conducted between 1992 and 2000, all schoolchildren 6 to 18 years old with glucosuria, proteinuria, or microscopic hematuria in repeated urine samples were included and received a physical examination and blood test. Those with gestational age <37 weeks were excluded. We enrolled 81,538 children (51,111 girls and 30,427 boys) and obtained their birth weights from the Taiwan Birth Registry. Obesity and hypertension were defined by age‐ and sex‐specific cut‐offs. Diabetes was diagnosed if the fasting glucose was >7 mM. Results: The risk of obesity was higher for those with birth weights ≥4000 grams [odds ratio (OR), 1.65] and 3543 to 3999 grams (OR, 1.28) and lower for those with birth weights 2601 to 2999 grams (OR, 0.90), using 3000 to 3542 grams as the reference group. An increased risk of diabetes was associated with both higher and lower birth weights, indicating a U‐shaped relationship (OR, <2600 grams, 1.607; 2601 to 2999 grams, 1.119; 3543 to 3999 grams, 1.112; ≥4000 grams, 1.661). In the 10‐ to 12‐year‐old age group, the risk of hypertension was higher in those with birth weights <2600 grams (OR, 1.20). Discussion: Low birth weight was associated with childhood diabetes. High birth weight was correlated with childhood obesity and diabetes. Our data indicate different relationships between birth weight and the development of obesity, hypertension, and diabetes in childhood.     

Frequency of family dinner and adolescent body weight status: evidence from the national longitudinal survey of youth, 1997

Objective: To explore associations between overweight status and the frequency of family dinners (FFD) for adolescents and how those associations differ across race and ethnicity. Research Methods and Procedures: A sample of 5014 respondents between 12 and 15 years of age from the 1997 wave of the National Longitudinal Survey of Youth 1997 (NLSY97) was used. BMI was calculated using self‐reported height and weight; 13.3% of respondents qualified as overweight, 16.4% qualified as at‐risk‐of‐overweight, and 1.9% qualified as underweight. The remainder were normal weight. FFD was defined as the number of times respondents had dinner with their families in a typical week in the past year. Multinomial logistic regression models were estimated separately for non‐Hispanic whites vs. blacks and Hispanics for odds of belonging to the other weight categories compared with normal weight. A supplementary longitudinal analysis estimated the odds of change in overweight status between 1997 and 2000. Results: In 1997, the FFD distribution was as follows: 0, 8.3%; 1 or 2, 7.3%; 3 or 4, 13.4%; 5 or 6, 28.1%; 7, 42%. For whites, higher FFD was associated with reduced odds of being overweight in 1997, reduced odds of becoming overweight, and increased odds of ceasing to be overweight by 2000. No such associations were found for blacks and Hispanics. Discussion: Reasons for racial and ethnic differences in the relationship between FFD and overweight may include differences in the types and portions of food consumed at family meals. More research is needed to verify this.     

Social stress and recovery: implications for body weight and body composition

Social stress resulting from dominant-subordinate relationships is associated with body weight loss and altered body composition in subordinate (SUB) male rats. Here, we extend these findings to determine whether stress-induced changes in energy homeostasis persist when the social stress is removed, and the animal is allowed to recover. We examined body weight (BW), body composition, and relevant endocrine measures after one or two cycles of 14 days of social stress, each followed by 21 days of recovery in each rat's individual home cage. SUB lost significantly more BW during social housing in a visible burrow system (VBS) compared with dominant (DOM) animals. Weight loss during social stress was attributable to a decrease in adipose tissue in DOM and SUB, with an additional loss of lean tissue in SUB. During both 21-day recovery periods, DOM and SUB regained lost BW, but only SUB were hyperphagic. Following recovery, SUB had a relatively larger increase in adipose tissue and plasma leptin compared with DOM, indicating that body composition changes were dependent on social status. Control animals that were weight matched to SUB or male rats exposed to the VBS environment without females, and that did not form a social hierarchy, did not exhibit changes in body composition like SUB in the VBS. Therefore, chronic social stress causes social status-dependent changes in BW, composition and endocrine measures that persist after repeated stress and recovery cycles and that may ultimately lead to metabolic disorders and obesity.     

Comparison of body composition methods in overweight and obese children.

The objective of the present study was to investigate the accuracy of percent body fat (%fat) estimates from dual-energy X-ray absorptiometry, air-displacement plethysmography (ADP), and total body water (TBW) against a criterion four-compartment (4C) model in overweight and obese children. A volunteer sample of 30 children (18 male and 12 female), age of (mean +/- SD) 14.10 +/- 1.83 yr, body mass index of 31.6 +/- 5.5 kg/m, and %fat (4C model) of 41.2 +/- 8.2%, was assessed. Body density measurements were converted to %fat estimates by using the general equation of Siri (ADPSiri) (Siri WE. Techniques for Measuring Body Composition. 1961) and the age- and gender-specific constants of Lohman (ADPLoh) (Lohman TG. Exercise and Sport Sciences Reviews. 1986). TBW measurements were converted to %fat estimates by assuming that water accounts for 73% of fat-free mass (TBW73) and by utilizing the age- and gender-specific water contents of Lohman (TBWLoh). All estimates of %fat were highly correlated with those of the 4C model (r > or = 0.95, P < 0.001; SE < or = 2.14). For %fat, the total error and mean difference +/- 95% limits of agreement compared with the 4C model were 2.50, 1.8 +/- 3.5 (ADPSiri); 1.82, -0.04 +/- 3.6 (ADPLoh); 2.86, -2.0 +/- 4.1 (TBW73); 1.90, -0.3 +/- 3.8 (TBWLoh); and 2.74, 1.9 +/- 4.0 DXA (dual-energy X-ray absorptiometry), respectively. In conclusion, in overweight and obese children, ADPLoh and TBWLoh were the most accurate methods of measuring %fat compared with a 4C model. However, all methods under consideration produced similar limits of agreement.     

Birth weight and cognitive function in the British 1946 birth cohort: longitudinal population based study

Objective: To examine the association between birth weight and cognitive function in the normal population. Design: A longitudinal, population based, birth cohort study. Participants: 3900 males and females born in 1946. Main outcome measures: Cognitive function from childhood to middle life (measured at ages 8, 11, 15, 26, and 43 years). Results: Birth weight was significantly and positively associated with cognitive ability at age 8 (with an estimated standard deviation score of 0.44 (95% confidence interval 0.28 to 0.59)) between the lowest and highest birthweight categories after sex, father's social class, mother's education, and birth order were controlled for. This association was evident across the normal birthweight range (>2.5 kg) and so was not accounted for exclusively by low birth weight. The association was also observed at ages 11, 15, and 26, and weakly at age 43, although these associations were dependent on the association at age 8. Birth weight was also associated with education, with those of higher birth weight more likely to have achieved higher qualifications, and this effect was accounted for partly by cognitive function at age 8. Conclusions: Birth weight was associated with cognitive ability at age 8 in the general population, and in the normal birthweight range. The effect at this age largely explains associations between birth weight and cognitive function at subsequent ages. Similarly, the association between birth weight and education was accounted for partly by earlier cognitive scores.     

QTLs for pre- and postweaning body weight and body composition in selected mice

In an intercross between the high-body-weight-selected mouse line NMRI8 and the inbred line DBA/2, we analyzed genetic effects on growth during the suckling period and after weaning during the juvenile phase of development. QTL mapping results indicated that a switch of gene activation might occur at the age of three weeks when animals are weaned. We found QTLs for body weight with major effects at the age of two and three weeks when animals are fed by their mothers, and QTLs with highest effects after weaning when animals have to live on their own under ad libitum access to food. Specific epistatic effects on body weight at two and three weeks and epistatic interaction influencing growth after weaning support this finding. QTL effects explained the greatest variance during puberty when animals grow fastest and become fertile. In the present study, all except one QTL effect for early body weight had dominance variance components. These might result from direct single-locus-dominant allelic expression, but also from the identified epistatic interaction between different QTLs that we have found for body weight at all ages. Beside body weight, body composition traits (muscle weight, reproductive fat weight, weight of inner organs) were analyzed. Sex-dimorphic QTLs were found for body weight and fat deposition. The identified early-growth QTLs could be the target of epigenetic modifications which might influence body weight at later ages.     

Growth and body composition of mice selected for high body weight

To elucidate the influence of high body weight selection on body compositional relationships, the accumulation of lipid, protein, and ash was investigated in two lines of mice selected for high 42-day body weight (H lines) and an unselected foundation population (FP). The two H lines differed in population size and were designated as the high-large (HL) and high-small (HS) lines. Logistic body growth curves revealed that HL mice exhibited an accelerated growth rate and reached a higher mature body weight than FP or HS mice. Over the range of body weights examined, HL mice had more lipid, less protein, and less ash than FP or HS mice of the same sex and body weight. However, HL lipid accumulation (relative to body weight increase) was not accelerated in comparison to that of FP mice. This study suggests that the existing model of selection-mediated compositional changes requires expansion to account for the ability of high-growth selection to direct an acceleration of body growth without a correlated enhancement of the relative rate of fat accumulation.     

Variation in the FFAR1 gene modifies BMI, body composition and beta-cell function in overweight subjects: an exploratory analysis

Background

FFAR1 receptor is a long chain fatty acid G-protein coupled receptor which is expressed widely, but found in high density in the pancreas and central nervous system. It has been suggested that FFAR1 may play a role in insulin sensitivity, lipotoxicity and is associated with type 2 diabetes. Here we investigate the effect of three common SNPs of FFAR1 (rs2301151; rs16970264; rs1573611) on pancreatic function, BMI, body composition and plasma lipids.

Methodology/Principal Findings

For this enquiry we used the baseline RISCK data, which provides a cohort of overweight subjects at increased cardiometabolic risk with detailed phenotyping. The key findings were SNPs of the FFAR1 gene region were associated with differences in body composition and lipids, and the effects of the 3 SNPs combined were cumulative on BMI, body composition and total cholesterol. The effects on BMI and body fat were predominantly mediated by rs1573611 (1.06 kg/m² higher (P = 0.009) BMI and 1.53% higher (P = 0.002) body fat per C allele). Differences in plasma lipids were also associated with the BMI-increasing allele of rs2301151 including higher total cholesterol (0.2 mmol/L per G allele, P = 0.01) and with the variant A allele of rs16970264 associated with lower total (0.3 mmol/L, P = 0.02) and LDL (0.2 mmol/L, P<0.05) cholesterol, but also with lower HDL-cholesterol (0.09 mmol/L, P<0.05) although the difference was not apparent when controlling for multiple testing. There were no statistically significant effects of the three SNPs on insulin sensitivity or beta cell function. However accumulated risk allele showed a lower beta cell function on increasing plasma fatty acids with a carbon chain greater than six.

Conclusions/Significance

Differences in body composition and lipids associated with common SNPs in the FFAR1 gene were apparently not mediated by changes in insulin sensitivity or beta-cell function.     

Effects of diet macronutrient composition on body composition and fat distribution during weight maintenance and weight loss

Objective: Neurotransmitter systems participate in the regulation of food intake, and their activities are expected to influence eating behavior. Design and Methods: We investigated possible associations between body mass index (BMI) and central noradrenaline, serotonin, and dopamine activities, as reflected by the cerebrospinal fluid levels of their main metabolites methoxyhydroxyphenylglycol (MHPG), 5‐hydroxyindoleacetic acid (5‐HIAA), and homovanillic acid (HVA), respectively. We studied 192 subjects (111 males, 81 females) admitted to neurologic clinic for diagnostic investigations that included CSF analysis, and were found not to suffer from any major neurological disease. Subjects were categorized in three groups, namely in lower, in the two middle, and in upper BMI quartiles, the limits calculated separately for males and females. Results: No differences were found in MHPG levels between groups, while subjects in the upper BMI quartile showed significantly elevated levels of 5‐HIAA and HVA compared to the levels of subjects in lower and middle quartiles. Conclusions: The results provide evidence that in overweight subjects there are enhanced demands in serotoninergic and dopaminergic signaling for their reward system that may lead to increased motivation for food consumption. The implication of reward centers in eating behavior supports the hypothesis of common mechanisms in obesity and drug addiction.     

Environmental maternal influences on body composition in mice selected for body weight

Summary The effect of the postnatal maternal environment, simulated by rearing mice in litters of three, six or nine, on body weight and body composition was investigated in three lines of mice differing widely in growth rate. The lines were selected for high (H₆) and low (L₆) 6-week body weight while the control line was maintained by random selection. Body weight and weights and percentages of ether extract, water, ash and protein at 21, 42, 63 and 84 days were recorded. With few exceptions, there were positive correlated responses to selection in body weight and in weights of body components. At 21 and 42 days the correlated responses were larger in L₆ mice than in H₆ mice. Body weight and weights of body components were larger for mice reared in litters of three than for those reared in litters of nine. Also, mice reared in litters of six were intermediate in body weight and weights of some of the body components between those reared in litters of three and nine. Differences in body weight and weights of body components due to postnatal maternal environment were small by comparison with differences due to genetic line. There were significant line by maternal environment interactions in body weight at 21 days and in ether extract weight at 21 and 63 days. Line and maternal environment differences in percentages of body components did not follow any consistent trend. The results for percentages of body components were further complicated by line x maternal environment interactions. In general, both line and postnatal maternal environmental differences in percentages of body components diminished with age.Paper No. 5670 of the Journal Series of the North Carolina Agricultural Experiment Station, Raleigh, North Carolina 27650. The use of trade names in this publication does not imply endorsement by the North Carolina Agricultural Experiment Station of the products named, nor criticism of similar ones not mentioned     

Relationship between body composition, inflammation and lung function in overweight and obese asthma

Background

The obese-asthma phenotype is not well defined. The aim of this study was to examine both mechanical and inflammatory influences, by comparing lung function with body composition and airway inflammation in overweight and obese asthma.

Methods

Overweight and obese (BMI 28-40 kg/m²) adults with asthma (n = 44) completed lung function assessment and underwent full-body dual energy x-ray absorptiometry. Venous blood samples and induced sputum were analysed for inflammatory markers.

Results

In females, android and thoracic fat tissue and total body lean tissue were inversely correlated with expiratory reserve volume (ERV). Conversely in males, fat tissue was not correlated with lung function, however there was a positive association between android and thoracic lean tissue and ERV. Lower body (gynoid and leg) lean tissue was positively associated with sputum %neutrophils in females, while leptin was positively associated with android and thoracic fat tissue in males.

Conclusions

This study suggests that both body composition and inflammation independently affect lung function, with distinct differences between males and females. Lean tissue exacerbates the obese-asthma phenotype in females and the mechanism responsible for this finding warrants further investigation.     

Birth weight,adult body size,and risk of colorectal cancer

BackgroundEvidence suggests that birth weight may be associated with colorectal cancer (CRC) risk later in life. Whether the association is mediated by adult body size remains unexamined.MethodCox proportional hazards models (Hazard Ratio (HR) and 95 % Confidence Intervals (CI)) were used to evaluate the association between self-reported birth weight (<6 lbs, 6-<8 lbs, ≥8 lbs) and CRC risk among 70,397 postmenopausal women from the Women’s Health Initiative. Further, we assessed whether this association was mediated by adult body size using multiple mediation analyses.ResultsCompared with birth weights of 6-< 8 lbs, birth weight ≥ 8 lbs was associated with higher CRC risk in postmenopausal women (HR = 1.31, 95 % CI 1.16–1.48). This association was significantly mediated by adult height (proportion mediated =11.4 %), weight (11.2 %), waist circumference (10.9 %), and body mass index at baseline (4.0 %). The joint effect of adult height and weight explained 21.6 % of this positive association.ConclusionOur data support the hypothesis that the intrauterine environment and fetal development may be related to the risk of developing CRC later in life. While adult body size partially explains this association, further investigation is required to identify other factors that mediate the link between birth weight and CRC.     

Disordered eating attitudes and behaviors in overweight youth

Disordered eating attitudes and behaviors appear to be quite common in youth, and overweight youth have been identified as a subset of the population at particularly high risk for endorsing such symptoms. Overweight and eating disorder (ED) symptomatology independently confer significant threats to one's physical and psychosocial health, showing strong links with body weight gain and risk for ED development. When concurrent, the risk for negative health outcomes may be compounded. The purpose of this article is to review the current state of the literature as it concerns disordered eating and its correlates in overweight children and adolescents. Extant literature on the prevalence, distribution, correlates, and etiology of disordered eating attitudes and behaviors (i.e., negative attitudes toward shape and weight, unhealthy weight control behaviors, and binge eating) in overweight youth is reviewed and consolidated in order to make assessment and treatment recommendations for healthcare providers. The current literature suggests that early detection of disordered eating in overweight youth should be a priority to provide appropriate intervention, thereby helping to slow the trajectory of weight gain and prevent or reduce the long-term negative consequences associated with both conditions. Future research should focus on explicating developmental pathways, and on developing novel prevention and treatment interventions for overweight youth exhibiting disordered eating patterns.