[Show abstract][Hide abstract] ABSTRACT: The SH3-domain GRB2-like (endophilin)-interacting protein 1 (SGIP1) gene has been shown to be differentially expressed in the hypothalamus of lean versus obese Israeli sand rats (Psammomys obesus), and is suspected of having a role in regulating food intake. The purpose of this study was to assess the role of genetic variation in SGIP1 in human disease.
We performed single-nucleotide polymorphism (SNP) genotyping in a large family pedigree cohort from the island of Mauritius. The Mauritius Family Study (MFS) consists of 400 individuals from 24 Indo-Mauritian families recruited from the genetically homogeneous population of Mauritius. We measured markers of the metabolic syndrome, including diabetes and obesity-related phenotypes such as fasting plasma glucose, waist:hip ratio, body mass index and fat mass.
Statistical genetic analysis revealed associations between SGIP1 polymorphisms and fat mass (in kilograms) as measured by bioimpedance. SNP genotyping identified associations between several genetic variants and fat mass, with the strongest association for rs2146905 (P=4.7 × 10(-5)). A strong allelic effect was noted for several SNPs where fat mass was reduced by up to 9.4% for individuals homozygous for the minor allele.
Our results show association between genetic variants in SGIP1 and fat mass. We provide evidence that variation in SGIP1 is a potentially important determinant of obesity-related traits in humans.
International journal of obesity (2005) 03/2011; 36(2):201-6. DOI:10.1038/ijo.2011.67 · 5.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metabolic syndrome is a group of disorders involving obesity, insulin resistance, dyslipidemia and hypertension. Obesity is the most crucial risk factor of metabolic syndrome, because it is known to precede other risk factors. Obesity is also associated with disturbances in the metabolism of the trace mineral, zinc. The overall purpose of this study was to investigate the effects of short-term weight loss on plasma zinc and metabolic syndrome risk factors. An 8-week weight loss intervention study was conducted with 90 low-income overweight/obese mothers, whose youngest child was 1-3 years old. Plasma levels of zinc, glucose, insulin, leptin, triglycerides, total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol were measured and compared at weeks 0 and 8 of the weight loss program. At pre-study, plasma zinc was low in 39% and, within normal values in 46%, of obese/overweight mothers. By the end of intervention, plasma zinc rose by 22% and only 5% of the mothers continued to exhibit low plasma zinc. At post-study, the metabolic syndrome risk factors of waist circumference, HDL cholesterol, and diastolic blood pressure (p<0.05) showed significant improvements. Plasma zinc increased by a greater margin (67%) in women with low zinc, as compared to those with normal zinc (18%); weight reduction was similar in both the groups. Finally, changes in % body fat were related negatively with changes in plasma zinc (r=- 0.28, p<0.05). The circulating levels of zinc, as well as the metabolic syndrome components, showed significant improvements in overweight/obese low-income women after weight loss.
Journal of Trace Elements in Medicine and Biology 10/2010; 24(4):271-6. DOI:10.1016/j.jtemb.2010.05.001 · 2.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Melanocortin-4-receptor (MC4R) haploinsufficiency is the most common form of monogenic obesity; however, the frequency of MC4R variants and their functional effects in general populations remain uncertain.
The aim was to identify and characterize the effects of MC4R variants in Hispanic children.
MC4R was resequenced in 376 parents, and the identified single nucleotide polymorphisms (SNPs) were genotyped in 613 parents and 1016 children from the Viva la Familia cohort. Measured genotype analysis (MGA) tested associations between SNPs and phenotypes. Bayesian quantitative trait nucleotide (BQTN) analysis was used to infer the most likely functional polymorphisms influencing obesity-related traits.
Seven rare SNPs in coding and 18 SNPs in flanking regions of MC4R were identified. MGA showed suggestive associations between MC4R variants and body size, adiposity, glucose, insulin, leptin, ghrelin, energy expenditure, physical activity, and food intake. BQTN analysis identified SNP 1704 in a predicted micro-RNA target sequence in the downstream flanking region of MC4R as a strong, probable functional variant influencing total, sedentary, and moderate activities with posterior probabilities of 1.0. SNP 2132 was identified as a variant with a high probability (1.0) of exerting a functional effect on total energy expenditure and sleeping metabolic rate. SNP rs34114122 was selected as having likely functional effects on the appetite hormone ghrelin, with a posterior probability of 0.81.
This comprehensive investigation provides strong evidence that MC4R genetic variants are likely to play a functional role in the regulation of weight, not only through energy intake but through energy expenditure.
American Journal of Clinical Nutrition 11/2009; 91(1):191-9. DOI:10.3945/ajcn.2009.28514 · 6.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to analyze the heritability and the presence of pleiotropic effects on subfractions of high-density lipoproteins (HDLs) as measured by nuclear magnetic resonance (NMR), parameters for adiposity, and glucose metabolism in adult Alaskan Eskimos. The present family study included 1,214 adult Alaskan Eskimos (537 male/677 female). Body weight, height, circumferences, selected skinfolds, and blood pressure were measured in all participants. Blood samples were collected under fasting conditions for the isolation of plasma. Glucose, insulin, subclasses and size of lipoproteins, triglycerides, total, and HDL cholesterol and lipoprotein (a) were measured in plasma. HbA1c was measured in total blood. Univariate and bivariate quantitative genetic analyses were conducted between HDL subclasses and size and the anthropometric and biochemical measures using the variance decomposition approach. Variation in all the analyzed traits exhibits a significant genetic component. Heritabilities ranged between 0.18 +/- 0.11 for LDL(2) (intermediate) and 0.89 +/- 0.07 for small HDL. No common genetic effects were found on the HDL subclasses (small, intermediate, and large). Small HDL particles were genetically correlated with LDL particles and HbA1c. Negative genetic correlations were observed between intermediate and large HDL subfractions, HDL size and measures of adiposity, and LDL and parameters for glucose metabolism (HbA1, insulin). These observations confirm the presence of possible pleiotropic effects on HDL, adiposity, and cardiovascular risk factors and provide novel insight on the relationship between HDL subclasses, adiposity, and glucose regulation.
American Journal of Human Biology 07/2009; 22(4):444-8. DOI:10.1002/ajhb.21015 · 1.93 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cytokines are considered to be involved in obesity-related metabolic diseases. Study objectives are to determine the heritability of circulating cytokine levels, to investigate pleiotropy between cytokines and obesity traits, and to present genome scan results for cytokines in 1030 Hispanic children enrolled in VIVA LA FAMILIA Study. Cytokine phenotypes included monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-alpha), leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), transforming growth factor beta 1 (TGF-beta1), C-reactive protein (CRP), regulated upon activation, normal T-cell expressed and secreted (RANTES) and eotaxin. Obesity-related phenotypes included body mass index (BMI), fat mass (FM), truncal FM and fasting serum insulin. Heritabilities ranged from 0.33 to 0.97. Pleiotropy was observed between cytokines and obesity traits. Positive genetic correlations were seen between CRP, leptin, MCP-1 and obesity traits, and negative genetic correlations with adiponectin, ICAM-1 and TGF-beta1. Genome-wide scan of sICAM-1 mapped to chromosome 3 (LOD=3.74) between markers D3S1580 and D3S1601, which flanks the adiponectin gene (ADIPOQ). Suggestive linkage signals were found in other chromosomal regions for other cytokines. In summary, significant heritabilities for circulating cytokines, pleiotropy between cytokines and obesity traits, and linkage for sICAM-1 on chromosome 3q substantiate a genetic contribution to circulating cytokine levels in Hispanic children.
[Show abstract][Hide abstract] ABSTRACT: Genome-wide scans were conducted in search for genetic locations linked to energy expenditure and substrate oxidation in children.
Pedigreed data of 1030 Hispanic children and adolescents were from the Viva La Familia Study which was designed to investigate genetic and environmental risk factors for the development of obesity in Hispanic families. A respiratory calorimeter was used to measure 24-h total energy expenditure (TEE), basal metabolic rate (BMR), sleep metabolic rate (SMR), 24-h respiratory quotient (24RQ), basal metabolic respiratory quotient (BMRQ) and sleep respiratory quotient (SRQ). Protein, fat and carbohydrate oxidation (PROOX, FATOX and CHOOX, respectively) were also estimated. All participants were genotyped for 384 single tandem repeat markers spaced an average of 10 cM apart. Computer program SOLAR was used to perform the genetic linkage analyses.
Significant linkage for TEE was detected on chromosome 1 near marker D1S2841, with a logarithm of the odds (LOD) score of 4.0. SMR, BMRQ and PROOX were associated with loci on chromosome 18, 17 and 9, respectively, with LOD scores of 4.88, 3.17 and 4.55, respectively. A genome-wide scan of SMR per kg fat-free mass (SpFFM) peaked in the same region as SMR on chromosome 18 (LOD, 5.24). Suggestive linkage was observed for CHOOX and FATOX. Several candidate genes were found in the above chromosomal regions including leptin receptor (LEPR).
Regions on chromosomes 1, 9, 17 and 18 harbor genes affecting variation in energy expenditure and substrate oxidation in Hispanic children and adolescents.
International journal of obesity (2005) 05/2008; 32(4):579-85. DOI:10.1038/ijo.2008.20 · 5.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to evaluate a nutrition and physical activity program for reducing body weight and improving nutrition attitudes in mothers of young children. A convenience sample of 114 intervention mothers and 33 comparison mothers was recruited from public health clinics and community centers. Eligibility criteria included Hispanic, African American, or white ethnicity; body mass index of at least 25 kg/m(2); low income (< 200% of the federal poverty index); and youngest child aged 1 to 4 years. For intervention participants, height, weight, percentage of body fat, waist circumference, demographics, nutrition attitudes, and dietary intake were measured at weeks 0 and 8; height, weight, percentage of body fat, and waist circumference were reassessed at 6 months. Overweight mothers in the comparison group provided anthropometric and demographic data at weeks 0 and 8. Changes in anthropometrics, attitudes, and dietary intake were evaluated in intervention mothers. Anthropometric data of intervention vs comparison group mothers were examined. Differences in anthropometrics and attitude scores between weight loss responders (> or = 2.27 kg) and nonresponders (< 2.27 kg) were assessed at week 8. Intervention participants lost weight (x = -2.7 kg; P < .001), whereas comparison mothers gained a slight amount of weight (x = 0.1 kg) by week 8. Weight loss responders had healthier eating attitudes (5.6 vs 5.2; P < .01) and fewer perceived barriers (2.4 vs 2.9; P < .05) than nonresponders postintervention. In conclusion, this dietary and physical activity curriculum is a valuable resource for weight management programs serving low-income women.
Nutrition research 01/2008; 28(1):13-20. DOI:10.1016/j.nutres.2007.11.005 · 2.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The prevalence of childhood obesity has increased dramatically in the United States. Early presentation of type 2 diabetes has been observed in children and adolescents, especially in the Hispanic population. The genetic contribution of glucose homeostasis related to childhood obesity is poorly understood. The objective of this study was to localize quantitative trait loci influencing fasting serum glucose levels in Hispanic children participating in the Viva La Familia Study.
Subjects were 1030 children ascertained through an overweight child from 319 Hispanic families. Fasting serum glucose levels were measured enzymatically, and genetic linkage analyses were conducted using SOLAR software.
Fasting glucose was heritable, with a heritability of 0.62 +/- 0.08 (P < 0.01). Genome-wide scan mapped fasting serum glucose to markers D13S158-D13S173 on chromosome 13q (LOD score of 4.6). A strong positional candidate gene is insulin receptor substrate 2, regulator of glucose homeostasis and a candidate gene for obesity. This region was reported previously to be linked to obesity- and diabetes-related phenotypes.
A quantitative trait locus on chromosome 13q contributes to the variation in fasting serum glucose levels in Hispanic children at high risk for obesity.
[Show abstract][Hide abstract] ABSTRACT: Although previous genome scans have searched for quantitative-trait loci (QTLs) influencing variation in blood pressure (BP), few have investigated the rate of change in BP over time as a phenotype. Here, we compare results from genomewide scans to localize QTLs for systolic, diastolic, and mean arterial BPs (SBP, DBP, and MBP, respectively) and for rates of change in systolic, diastolic, and mean arterial BPs (rSBP, rDBP, and rMBP, respectively), with use of the longitudinal data collected about Mexican Americans of the San Antonio Family Heart Study (SAFHS). Significant evidence of linkage was found for rSBP (LOD 4.15) and for rMBP (LOD 3.94) near marker D11S4464 located on chromosome 11q24.1. This same chromosome 11q region also shows suggestive linkage to SBP (LOD 2.23) and MBP (LOD 2.37) measurements collected during the second clinic visit. Suggestive evidence of linkage to chromosome 5 was also found for rMBP, to chromosome 16 for rSBP, and to chromosomes 1, 5, 6, 7, and 21 for the single-time-point BP traits collected at the first two SAFHS clinic visits. We also present results from fine mapping the chromosome 11 QTL with use of SNP-association analysis within candidate genes identified from a bioinformatic search of the region and from whole-genome transcriptional expression data collected from 1,240 SAFHS participants. Our results show that the use of longitudinal BP data to calculate the rate of change in BP over time provides more information than do the single-time measurements, since they reveal physiological trends in the subjects that a single-time measurement could never capture. Further investigation of this region is necessary for the identification of the genetic variation responsible for QTLs influencing the rate of change in BP.
The American Journal of Human Genetics 11/2007; 81(4):744-55. DOI:10.1086/521151 · 10.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study was conducted to investigate genetic influence on serum ghrelin and its relationship with adiposity-related phenotypes in Hispanic children (n=1030) from the Viva La Familia study (VFS). Anthropometric measurements and levels of serum ghrelin were estimated and genetic analyses conducted according to standard procedures. Mean age, body mass index (BMI), and serum ghrelin were 11+/-0.13 y, 25+/-0.24 kg/m2 and 38+/-0.5 ng/mL, respectively. Significant heritabilities (p<0.001) were obtained for BMI, weight, fat mass, percent fat, waist circumference, waist-to-height ratio, and ghrelin. Bivariate analyses of ghrelin with adiposity traits showed significant negative genetic correlations (p<0.0001) with weight, BMI, fat mass, percent fat, waist circumference, and waist-to-height ratio. A genome-wide scan for ghrelin detected significant linkage on chromosome 1p36.2 between STR markers D1S2697 and D1S199 (LOD=3.2). The same region on chromosome 1 was the site of linkage for insulin (LOD=3.3), insulinlike growth factor binding protein 1 (IGFBP1) (LOD=3.4), homeostatic model assessment method (HOMA) (LOD=2.9), and C-peptide (LOD=2.0). Several family-based studies have reported linkages for obesity-related phenotypes in the region of 1p36. These results indicate the importance of this region in relation to adiposity in children from the VFS.
Pediatric Research 10/2007; 62(4):445-50. DOI:10.1203/PDR.0b013e31813cbf02 · 2.84 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Birth weight has been shown to be associated with obesity and metabolic diseases in adulthood, however, the genetic contribution is still controversial. The objective of this analysis is to explore the genetic contribution to the relationship between birth weight and later risk for obesity and metabolic diseases in Hispanic children. Subjects were 1,030 Hispanic children in the Viva La Familia Study. Phenotypes included body size, body composition, blood pressure, fasting glucose, insulin, lipids, and liver enzymes. Birth weights were obtained from Texas birth certificates. Quantitative genetic analyses were conducted using SOLAR software. Birth weight was highly heritable, as were all other phenotypes. Phenotypically, birth weight was positively correlated to childhood body size parameters. Decomposition of these phenotypic correlations into genetic and environmental components revealed significant genetic correlations, ranging from 0.30 to 0.59. Negative genetic correlations were seen between birth weight and lipids. The genome scan of birth weight mapped to a region near marker D10S537 (LOD = 2.6). The bivariate genome-wide scan of birth weight and childhood weight or total cholesterol, improved the LOD score to 3.09 and 2.85, respectively. Chromosome 10q22 harbors genes influencing both birth weight and childhood body size and cardiovascular disease risk in Hispanic children.
Human Genetics 08/2007; 121(6):737-44. DOI:10.1007/s00439-007-0366-7 · 4.52 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite the high prevalence of overweight among Hispanic children in the United States, definitive predictors of weight gain have not been identified in this population.
The study objective was to test sociodemographic, metabolic, and behavioral predictors of 1-y weight gains in a large cohort of Hispanic children studied longitudinally.
Subjects (n = 879) were siblings from 319 Hispanic families enrolled in the Viva la Familia Study. Families were required to have at least one overweight child aged 4-19 y. One-year changes in weight and body composition by dual-energy X-ray absorptiometry were measured. Data were from parental interviews, birth certificates, multiple-pass 24-h dietary recalls, 3-d accelerometry, 24-h respiration calorimetry, measurements of eating in the absence of hunger, and measurement of fasting blood biochemistry indexes by radioimmunoassay. Generalized estimating equations and principal component analysis were applied.
Weight gain increased with age (P = 0.001), peaking at approximately 10 y of age in girls and approximately 11 y of age in boys. Mean (+/-SD) weight gain was significantly higher in overweight (7.5 +/- 3.7 kg/y) than in nonoverweight (4.4 +/- 2.4 kg/y) children and in boys than in girls. When adjusted for age, age squared, sex, and Tanner stage, the final model indicated a child's body mass index (BMI; kg/m2) status, maternal BMI, energy expenditure (total energy expenditure, basal metabolic rate, and sleeping metabolic rate), and fasting blood biochemistry indexes (total triiodothyronine, insulin, leptin, and ghrelin) as independent, positive predictors of weight gain (P = 0.01-0.001).
Knowledge of the metabolic and behavioral predictors of weight gain in Hispanic children will inform prevention and treatment efforts to address this serious public health problem in the United States.
American Journal of Clinical Nutrition 07/2007; 85(6):1478-85. · 6.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To examine the effects of a weight loss program for mothers on the diet and activity of mothers and their 1-3 year old children.
Overweight and obese mothers participated in an 8-week weight loss intervention encompassing diet, physical activity, and behavioral modification. Anthropometrics, demographic, dietary, and physical activity questionnaires were administered at weeks 0 and 8; anthropometrics were re-evaluated at week 24.
Mothers (N=91) of a 1-3 year old child; body mass index (BMI) >or= 25 kg/m2; non-breastfeeding; age 18-45 years; income < 200% of federal poverty index; Hispanic, African American, or white; and English-speaking were recruited from Special Supplemental Program for Women Infants and Children (WIC) and public health clinics. INTERVENTION MEASURES OF OUTCOME: Weight loss in mothers and improvements in diet (reduction in calories, fat, snacks/desserts, sweetened beverages, and increases in fruit, vegetables) and activity in mothers and children.
Weight loss in mothers was modest (-2.7 kg, p < 0.001) and sustained at week 24 (-2.8 kg, p < 0.001), and children gained in height and weight as expected for normal growth (p < 0.001). Initial energy intakes of children exceeded Estimated Energy Requirements (123%) and were reduced to acceptable levels post-intervention (102%, p < 0.001); additional beneficial changes in children's diets were decreased total (47.7 to 39.9 g/day) and saturated fat (19.2 to 16.6 g/day), high-fat snacks/desserts (1.6 to 0.9 servings/day), added fats (81.8 to 40.9% using), sweetened beverages (0.8 to 0.4 servings/day), and fast food consumption (11.6 to 6.6% of meals), and increased home-prepared meals (63.2 to 71.6% of meals) (p < 0.01 for all). Physical activity scores improved by 7% in children (p < 0.05). Comparable changes in food choices and activity also were seen in mothers.
Offering weight loss classes was a successful method of enticing low-income women to participate in an educational intervention that benefited their children. Overweight and obese mothers who modified their food choices and fat habits made comparable changes for their child.
Journal of the American College of Nutrition 06/2007; 26(3):196-208. DOI:10.1080/07315724.2007.10719602 · 1.68 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Eating in the absence of hunger (EAH) may be a genetically influenced phenotype of overweight children, but evidence is limited. This research evaluated the heritability (h(2)) of EAH and its association with overweight among Hispanic children 5 to 18 years old. Genetic and environmental associations of EAH with overweight, fat mass, and key hormonal regulators of food intake were also evaluated.
A family design was used to study 801 children from 300 Hispanic families. Weighed food intakes were used to measure EAH after an ad libitum dinner providing 50% of estimated energy needs. Fasting ghrelin, amylin, insulin, and leptin were measured by immunoassays. Measured heights, weights, and fat mass (using DXA) were obtained. Total energy expenditure (TEE) was measured by room respiration calorimetry.
On average, children consumed 41% of TEE at the dinner meal, followed by an additional 19% of TEE in the absence of hunger. Overweight children consumed 6.5% more energy at dinner (p < 0.001) and 14% more energy in the absence of hunger (p < 0.001) than non-overweight children. Significant heritabilities were seen for EAH (h(2) = 0.51) and dinner intake (h(2) = 0.52) and for fasting levels of ghrelin (h(2) = 0.67), amylin (h(2) = 0.37), insulin (h(2) = 0.37), and leptin (h(2) = 0.34). Genetic correlations were seen between eating behavior and fasting hormones, suggesting common underlying genes affecting their expression.
This research provides new evidence that overweight Hispanic children exhibit elevated levels of hyperphagic eating behaviors that are influenced by genetic endowment.
[Show abstract][Hide abstract] ABSTRACT: The metabolic syndrome, as defined by the International Diabetes Federation, was investigated in five large, extended, highly consanguineous, healthy Omani Arab families of a total of 1277 individuals. Heritability (h2) of the phenotypic abnormalities that make up the syndrome and other related traits was estimated by variance decomposition method using SOLAR software. The overall prevalence of the syndrome was 23%. The prevalence of abnormalities making the syndrome in a descending order were: obligatory waist circumference, hypertension, raised fasting blood glucose, low serum high-density lipoprotein (HDL), and raised serum triglycerides (TGs). Highly significant, but widely spread, h2 values were obtained for: height (0.68), weight (0.68), BMI (0.68), serum HDL (0.63), serum leptin (0.55), percentage body fat (0.53), total serum cholesterol (0.53), fasting serum insulin (0.51), homeostasis model assessment-insulin resistance index (0.48), serum TG (0.43), waist circumference (0.40), diastolic blood pressure (0.38), and 2-hour glucose level (0.17), whereas for the metabolic syndrome itself, h2 was 0.38. The wide spread of h2 results (0.07 to 0.68) indicates that some determinants, such as weight, BMI, and HDL level, are under significant genetic influence among the Omani Arabs. Other determinants such as insulin resistance, abdominal obesity, diastolic blood pressure, and TG levels seem to be more environmentally driven.
[Show abstract][Hide abstract] ABSTRACT: Adiponectin, a hormone produced exclusively by adipose tissue, is inversely associated with insulin resistance and proinflammatory conditions. The aim of this study was to find quantitative trait loci (QTLs) that affect circulating levels of adiponectin in Hispanic children participating in the VIVA LA FAMILIA Study by use of a systematic genome scan.
The present study included extended families with at least one overweight child between 4 and 19 years old. Overweight was defined as body mass index (BMI) 95th percentile. Fasting blood was collected from 466 children from 127 families. Adiponectin was assayed by radioimmunoassay (RIA) technique in fasting serum. A genome-wide scan on circulating levels of adiponectin as a quantitative phenotype was conducted using the variance decomposition approach.
The highest logarithm of odds (LOD) score (4.2) was found on chromosome 11q23.2-11q24.2, and a second significant signal (LOD score=3.0) was found on chromosome 8q12.1-8q21.3. In addition, a signal suggestive of linkage (LOD score=2.5) was found between 18q21.3 and 18q22.3. After adjustment for BMI-Z score, the LOD score on chromosome 11 remained unchanged, but the signals on chromosomes 8 and 18 dropped to 1.6 and 1.7, respectively. Two other signals suggestive of linkage were found on chromosome 3 (LOD score=2.1) and 10 (LOD score=2.5). Although the region on chromosome 11 has been associated with obesity and diabetes-related traits in adult populations, this is the first observation of linkage in this region for adiponectin levels. Our suggestive linkages on chromosomes 10 and 3 replicate results for adiponectin seen in other populations. The influence of loci on chromosomes 18 and 8 on circulating adiponectin seemed to be mediated by BMI in the present study.
Our genome scan in children has identified a novel QTL and replicated QTLs in chromosomal regions previously shown to be linked with obesity and type 2 diabetes (T2D)-related phenotypes in adults. The genetic contribution of loci to adiponectin levels may vary across different populations and age groups. The strong linkage signal on chromosome 11 is most likely underlain by a gene(s) that may contribute to the high susceptibility of these Hispanic children to obesity and T2D.
International Journal of Obesity 04/2007; 31(3):535-42. DOI:10.1038/sj.ijo.0803436 · 5.39 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Genetic components of energy homeostasis contributing to childhood obesity are poorly understood. Genome scans were performed to identify chromosomal regions contributing to physical activity and dietary intake traits in Hispanic children participating in the VIVA LA FAMILIA Study.
We report linkage findings on chromosome 18 for physical activity and dietary intake in 1030 siblings from 319 Hispanic families. Measurements entailed physical activity by accelerometry, dietary intake by two 24-hour recalls, and genetic linkage analyses using SOLAR software.
Significant heritabilities were seen for physical activity and dietary intake, ranging from 0.46 to 0.69, except for vigorous activity (h2 = 0.18). Percentage time in sedentary activity mapped to markers D18S1102-D18S64 on chromosome 18 [logarithm of the odds (LOD) score = 4.07], where melanocortin 4 receptor gene (MC4R) resides. Quantitative trait loci (QTLs) for total activity counts, percentage time in light or in moderate activity, and carbohydrate intake and percentage of energy intake from carbohydrates were detected in the same region (LOD = 2.28, 2.79, 2.2, 1.84, and 1.51, respectively). A novel loss of function mutation in MC4R (G55V) was detected in six obese relatives, but not in the rest of the cohort. Removal of these MC4R-deficient subjects from the analysis reduced the LOD score for sedentary activity to 3.94.
Given its role in the regulation of food intake and energy expenditure, MC4R is a strong positional candidate gene for the QTL on chromosome 18 detected for physical activity and dietary intake in Hispanic children.
[Show abstract][Hide abstract] ABSTRACT: Genetic and environmental contributions to childhood obesity are poorly delineated.
The Viva la Familia Study was designed to genetically map childhood obesity and its comorbidities in the Hispanic population. The objectives of this report were to describe the study design and to summarize genetic and environmental contributions to the phenotypic variation in obesity and risk factors for metabolic diseases in Hispanic children.
The Viva la Familia cohort consisted of 1030 children from 319 families selected based on an overweight proband between the ages of 4 and 19 y. In-depth phenotyping to characterize the overweight children and their siblings included anthropometric and body-composition traits by dual-energy X-ray absorptiometry and assessments of diet by 24-h recalls, physical activity by accelerometry, and risk factors for metabolic diseases by standard biochemical methods. Univariate quantitative genetic analysis was used to partition phenotypic variance into additive genetic and environmental components by using the computer program SOLAR.
Sex, age, and environmental covariates explained 1-91% of the phenotypic variance. Heritabilities of anthropometric indexes ranged from 0.24 to 0.75. Heritability coefficients for the body-composition traits ranged from 0.18 to 0.35. Diet and physical activity presented heritabilities of 0.32 to 0.69. Risk factors for metabolic diseases were heritable with coefficients ranging from 0.25 to 0.73. Significant genetic correlations between obesity traits and risk factors for metabolic diseases substantiated pleiotropy between traits.
The Viva la Familia Study provides evidence of a strong genetic contribution to the high prevalence of obesity and its comorbidities in Hispanic children.
American Journal of Clinical Nutrition 10/2006; 84(3):646-54; quiz 673-4. · 6.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Increasing incidence of cardiovascular disease in traditionally low-risk Alaskan Eskimos is a cause for concern. The purpose of this study was to examine the genetic and environmental correlations of low-density lipoprotein (LDL) subfractions with obesity-related factors in Alaskan Eskimos, using data from the first 954 participants of the Genetics of Coronary Artery Disease in Alaska Natives Study. Estimates of genetic and environmental influence were calculated using a maximum likelihood variance component method implemented in SOLAR. Mean values of weight, body mass index (BMI), and waist were 73.4 +/- 0.5 kg, 27.6 +/- 0.2 kg/m2, and 88.0 +/- 0.4 cm, respectively. LDL, and its small (LDL1), medium (LDL2), and large (LDL3) subfractions, had mean values of 115.8 +/- 1.2 mg/dl, 8.3 +/- 0.4 mg/dl, 19.6 +/- 0.8 mg/dl, and 71.5 +/- 1.5 mg/dl, respectively. Bivariate analysis displayed significant genetic correlations between LDL subfractions and obesity-related factors: LDL1 with BMI (rhoG = 0.67, P < 0.05), waist (rhoG = 0.80, P < 0.001), and subscapular and tricep skinfolds (rhoG = 0.93, P < 0.005, and rhoG = 0.78, P < 0.05, respectively); LDL2 with BMI (rhoG = 0.52, P < 0.05), waist (rhoG = 0.46, P < 0.05), and tricep skinfold (rhoG = 0.60, P < 0.05); and mean LDL size with BMI (rhoG = -0.36), waist (rhoG = -0.42,), and subscapular and tricep skinfolds (rhoG = -0.44 and -0.43, respectively) (P < 0.005). These results show that a common set of genes is influencing LDL size and obesity-related factors in Alaskan Eskimos.
American Journal of Human Biology 07/2006; 18(4):525-31. DOI:10.1002/ajhb.20527 · 1.93 Impact Factor