Familial resemblance of body composition in prepubertal girls and their biological parents 1 4

Transcription

1 Familial resemblance of body composition in prepubertal girls and their biological parents 1 4 Margarita S Treuth, Nancy F Butte, Kenneth J Ellis, Lisa J Martin, and Anthony G Comuzzie ABSTRACT Background: Heritability estimates for body mass index (BMI; in kg/m 2 ) in children generally have been derived from twin and adoption studies. However, BMI does not reflect total or regional body composition. Objective: We evaluated the familial resemblance of body composition between prepubertal girls of normal weight and body fatness and their parents by using state-of-the-art technology. Design: The subjects were 101 girls [mean age: 8.5 ± 0.4 y; percentage body fat (%BF): 12 30%] and their biological parents. Weight, height, and body composition [fat mass (FM), fat-free mass (FFM), and %BF] were measured with dual-energy X-ray absorptiometry (DXA) and total body potassium (TBK). Results: Weight, height, and BMI showed low-to-moderate similarity between the girls and both their parents (r = , P < 0.01). The girls FM, FFM, and %BF were significantly related to both parents body composition. Cross-generational equations were developed for DXA, eg, child s %BF = (0.158 paternal %BF) + (0.145 maternal %BF) (adjusted r 2 = 0.16, P < 0.001). Regional analysis with DXA showed that the adjusted r 2 values for the arm, trunk, and leg regions, respectively, were 0.17, 0.33, and 0.31 for lean tissue mass and 0.11, 0.14, and 0.09 for FM. TBK showed a similar relation between parents and girls (r = , P < 0.01). Significant heritability (h 2 ± SE) was detected for BMI (0.35 ± 0.17, P = 0.03) and %BF measured with DXA (0.50 ± 0.12, P = ). Conclusion: The body composition of prepubertal girls of normal weight and body fatness is significantly related to the body composition of both biological parents. Am J Clin Nutr 2001;74: KEY WORDS Obesity, girls, dual-energy X-ray absorptiometry, familial resemblance, total body potassium, body composition, heritability, fat mass, fat-free mass, body mass index, body fat INTRODUCTION Evidence suggests that both environmental and genetic factors play important roles in the development of obesity. Studies of twins reported heritability estimates for body mass index (BMI; weight in kg divided by the square of height in m) of 50 70% (1, 2), whereas adoption studies reported somewhat lower estimates of 20 30% (3 5). Four large family studies reported familial correlations for BMI ranging from 0.20 to 0.23 (6 9). Most of the studies that estimated the heritability of obesity used BMI as the measure of adiposity. However, BMI does not provide information about total or regional body composition, ie, the proportions of fat and lean tissue. Two studies overcame this limitation of BMI by using hydrodensitometry to measure percentage body fat (%BF) in Pima Indians (10) and in Canadians enrolled in the Quebec Family Study (6). The heritability estimates were reported as 0.76 and 0.20, respectively. The studies that examined body-composition correlations between parents and offspring were done primarily with adult offspring. One study of a large sample of 6- to 12-y-old children reported significant relations (no r value given, P = 0.04) between the BMI of the children and their parents (11). Family studies of body composition measured with sophisticated techniques are lacking. Dual-energy X-ray absorptiometry (DXA) provides accurate, precise measurements of bone mineral content (BMC), fat mass (FM), and fat-free mass (FFM). DXA can be used to examine both total body and regional (arms, legs, and trunk) values of these body-composition components. Because of its accuracy, DXA is being used more frequently for body-composition assessments in children. An older technique, total body potassium (TBK), can also be used to measure lean body mass but requires an instrument that typically is not available outside research settings. Thus, few facilities have the capability to measure body composition with both DXA and TBK in children. We used the DXA and TBK technology available at the US Department of Agriculture, Agricultural Research Service, 1 From the Center for Human Nutrition, Johns Hopkins University, Baltimore; the US Department of Agriculture, Agricultural Research Service, Children s Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston; and the Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX. 2 The contents of this publication do not necessarily reflect the views or policies of the US Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the US government. 3 Supported by NIH R29 HD34029 (to MT) and US Department of Agriculture Agricultural Research Service Cooperative Agreement D/01 (to MT, NB, and KE). 4 Address reprint requests to MS Treuth, Center for Human Nutrition, School of Hygiene and Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD mtreuth@jhsph.edu. Received October 20, Accepted for publication January 12, Am J Clin Nutr 2001;74: Printed in USA American Society for Clinical Nutrition 529

2 530 TREUTH ET AL TABLE 1 Characteristics of the prepubertal girls and their mothers and fathers 1 Girls Mothers Fathers (n = 101) (n = 101) (n = 101) Age (y) 8.5 ± ± ± 5.8 Weight (kg) 28.2 ± ± ± 17.1 Height (cm) ± ± ± 8.7 BMI (kg/m 2 ) 16.5 ± ± ± x ± SD. Children s Nutrition Research Center at Baylor College of Medicine to determine whether a familial resemblance of body composition could be found in biological parents and their prepubertal children. The specific aim of this study was to examine the total and regional BMC, FM, FFM, and %BF of prepubertal girls of normal weight and body fat and to compare these body-composition components with those of the girls biological parents. SUBJECTS AND METHODS Subjects Healthy prepubertal girls aged 8 9 y (n = 101) were recruited from the Houston area to participate in the study. All the girls were at Tanner stage I as confirmed by their mothers, who were shown drawings of the different Tanner stages. The girls were screened and had to be below the 90th percentile of weight for height (12) and have a %BF between 12% and 30% (as measured with DXA) to be included in the study. Girls with cardiovascular disease, anemia, diabetes, significant renal or hepatic disease, hypothyroidism, or musculoskeletal problems were excluded. The children and their parents provided written, informed consent to participate in the study, which was approved by the Institutional Review Board for Human Subject Research for Baylor College of Medicine and Affiliated Hospitals. Study protocol Body weight was measured to the nearest 0.1 kg with a digital balance (Scale-Tronix, Dallas). Height was measured to the nearest 1 cm with a stadiometer (Holtain Ltd, Crymych, United Kingdom). BMI was calculated as weight (kg) divided by height 2 (m). Dual-energy X-ray absorptiometry Body composition was measured by using DXA (model QDR 2000, pencil beam mode; software 5.56; Hologic, Madison, WI;). The subject lay supine on a bed and was scanned from head to toe in min. DXA allows for determination of bone mineral density (BMD), lean tissue mass (LTM), FM, and BMC. For the total body, FFM was defined as the sum of LTM and BMC. For each body-composition compartment, we determined separate regional values for the arms, legs, and trunk. Total body potassium TBK was measured with a low-background, multidetector, whole-body counter as described previously (13). 40 K, a radioactive isotope, is an intrinsic tracer (0.012%) for natural potassium. It decays, emitting a 1.46-MeV gamma ray that can be detected external to the body. For the weight range of the children and adults examined in this study, the precision of the TBK measurement is 1 2%. For healthy subjects, the intracellular potassium content can be assumed to be constant at 150 mmol/l (14). Furthermore, the ratio of TBK (mmol) to FFM (kg) for healthy adults can be assumed constant (60 and 64 for women and men, respectively) (15). The ratio of TBK to FFM changes during the growth of children (16); however, for the age group of the girls in this study, the ratio was assumed to be Statistical analysis Data are presented as means ± SDs. MICROSOFT ACCESS (version 7.0; Microsoft Corp, Seattle) was used for database management. Statistical analyses were performed with MINITAB (version 12.2; Minitab Inc, State College, PA); significance was set at P < Pearson s product-moment correlation coefficients were determined to examine the relations between the child s body composition and the paternal and maternal body composition separately. Regression analysis was used to determine the combined effect of paternal and maternal body composition. The independent variables included weight; height; BMI; total and regional BMC, FM, FFM, and %BF measured with DXA; and TBK, FM, FFM, and %BF measured with TBK. The model (y = P + 2 M + 3 P M) included the paternal (P) and maternal (M) measures of the variable of interest and the interaction term. Univariate quantitative genetic analysis was used to partition the phenotypic variance for each of the body-composition phenotypes into additive genetic and environmental variance components. The additive genetic heritability (h 2 ) of a trait represents the portion of the total phenotypic variance accounted for by the effects of genes (ie, h 2 = 2 genetic / 2 phenotypic ). The heritabilities were estimated by using the maximum likelihood variance decomposition method (17, 18) implemented in the computer program FISHER (19). Such an approach makes it possible to test whether correlations among family members for a specific trait (eg, BMI) are solely the result of the environment or whether genetic effects are also involved. In addition, the effects of sex and age and their interaction were simultaneously estimated as part of the analysis. RESULTS Subject characteristics Of the 101 prepubertal girls, 52 were white, 30 were African American, and 19 were Hispanic. We used the ethnicity of the mother to classify the ethnicity of the daughter. The ethnic distribution of the fathers was 56 white, 29 African American, and 16 Hispanic. Weight, height, and BMI values are shown in Table 1. The girls were all of normal weight and body fatness because of the selection criteria. Parental BMI varied greatly, ranging from normal weight to severely obese (range: for mothers and for fathers). Body-composition values (FM, FFM, and %BF) measured with DXA and TBK are shown in Table 2. Correlations between the girls and parents body-composition measures are shown in Table 3. The girls weight, height, and BMI were correlated with the weight, height, and BMI of both mothers and fathers. The highest correlation was observed between the girls BMI and the fathers BMI. Similarly, for FM, FFM, and %BF obtained with DXA, the girls values were correlated with both the mothers and the fathers values. The girls FM, FFM, and %BF values obtained with TBK were significantly related to both the mothers and fathers values.

3 BODY COMPOSITION IN GIRLS AND THEIR PARENTS 531 TABLE 2 Body composition measured with dual-energy X-ray absorptiometry (DXA) and total body potassium (TBK) in the prepubertal girls and their mothers and fathers 1 Fat mass Fat-free mass Percentage body fat kg kg % Girls DXA (n = 101) 6.1 ± ± ± 4.7 ( ) ( ) ( ) TBK (n = 99) 6.8 ± ± ± 5.5 ( ) ( ) ( ) Mothers DXA (n = 100) 31.1 ± ± ± 8.9 ( ) ( ) ( ) TBK (n = 101) 31.1 ± ± ± 9.1 ( ) ( ) ( ) Fathers DXA (n = 94) 21.6 ± ± ± 7.8 ( ) ( ) ( ) TBK (n = 93) 27.3 ± ± ± 7.9 ( ) ( ) ( ) 1 x ± SD; range in parentheses. The results of regression analysis showed no significant interactions between paternal and maternal values for weight or height; however, a significant interaction was observed for BMI. The regression equations for weight, height, and BMI are as follows: Weight of child = P M (adjusted r 2 = 0.22) (1) Height of child = P M (adjusted r 2 = 0.24) (2) BMI of child (with interaction term) = P M ( P M) (adjusted r 2 = 0.26) (3) BMI of child (without interaction term) = P M (adjusted r 2 = 0.22) (4) where all were significant at P < Significant heritability was detected for BMI (x ± SE: 0.35 ± 0.17; P = 0.03) and for %BF measured with DXA (0.50 ± 0.12; P = ). The proportion of the variance that resulted from the 2 covariates (sex and age) was 0.44 for BMI and 0.54 for %BF. No significant heritabilities were detected for FFM and FM. The regression equations relating the girls and parents values for total-body BMC and BMD measured with DXA, and for FM, FFM, and %BF measured with DXA and TBK are shown in Table 4. The BMC and BMD of the girls were significantly related to the BMC and BMD of both parents. There were no significant interactions between maternal and paternal values for total-body FM, FFM, and %BF measured with DXA or TBK (adjusted r 2 = ). The effect of paternal and maternal %BF measured with DXA on the girls %BF measured with DXA was significant (adjusted r 2 = 0.16). When parental age was entered, the adjusted r 2 values were 0.37 for total-body FFM and 0.16 for %BF measured with DXA. With the TBK method, the FFM of the father and mother had a significant influence on the girl s FFM measured with TBK (adjusted r 2 = 0.32; interaction included adjusted r 2 = 0.36). Also shown in Table 4 are the regression equations for BMC, FM, and LTM of the arms, trunk, and legs measured with DXA. There were significant effects of both paternal and maternal BMC (adjusted r 2 = ) on the BMC of the girls arms and trunk. For the arms, trunk, and legs, the adjusted r 2 values were lower for FM (0.11, 0.14, and 0.09, respectively) than for LTM (0.17, 0.33, and 0.37, respectively). The strongest predictive power was for the leg region, specifically for LTM (adjusted r 2 = 0.37). The maternal trunk FM did not significantly influence the girls trunk FM. The paternal FM, LTM, and %BF of the legs did not significantly influence the girls leg values. DISCUSSION In this study we examined the relations between the body composition of prepubertal girls and that of their mothers and fathers; %BF ranged from 12% to 30% in the girls. The heritability estimate was significant for BMI and %BF measured with DXA, with a higher heritability estimate for the %BF than for BMI. Our analyses showed that the body composition of the girls was significantly related to both their fathers and mothers body composition. This observation also held true in the analyses of specific body regions, except for FM of the legs and trunk. Our study examined the familial resemblance between parent and child of an anthropometric index, BMI. BMI was one trait that had a significant heritability estimate (0.35 ± 0.17) in our sample of prepubertal girls and their parents. In studies of twins, heritability estimates for BMI were reported to be 50 70% (1, 2). The correlations of BMI observed between the girls and their mothers (r = 0.34) and fathers (r = 0.44) were slightly higher than the values of that were reported previously in 4 large family studies (6 9). The relative strength of the correlations we found may indicate that a large proportion of the interindividual differences in BMI is the result of additional environmental influences, such as dietary energy intake and macronutrient composition and physical activity levels. The influence TABLE 3 Correlations between the prepubertal girls and their mothers and fathers for body-composition components measured with dual-energy X-ray absorptiometry (DXA) and total body potassium (TBK) 1 Mother Father Girls r P r P Weight Height BMI FM DXA TBK FFM DXA TBK %BF DXA TBK TBK FM, fat mass; FFM, fat-free mass; %BF, percentage body fat. n values were as follows: girls, 101 for DXA and 99 for TBK; mothers, 100 for DXA and 101 for TBK; fathers, 94 for DXA and 93 for TBK.

4 532 TREUTH ET AL TABLE 4 Linear regression analysis of fat mass (FM), fat-free mass (FFM), and percentage body fat (%BF) determined with dual-energy X-ray absorptiometry (DXA) and total body potassium (TBK) in the prepubertal girls and their mothers and their fathers 1 Equation Adjusted r 2 P (Father) P (Mother) P (Interaction) DXA: total body BMC P BMC M BMC BMD P BMD M BMD FM P FM M FM FFM P FFM M FFM %BF P %BF M %BF DXA: arms BMC P BMC + 95 M BMC FM P FM M FM LTM P LTM M LTM %BF P %BF M %BF DXA: trunk BMC P BMC M BMC FM P FM M FM LTM P LTM M LTM %BF P %BF M %BF DXA: legs BMC P BMC 624 M BMC P M BMC FM P FM M FM LTM P LTM 444 M LTM P M LTM %BF P %BF M %BF TBK TBK P TBK M TBK P M TBK FM P FM M FM FFM P FFM M FFM %BF P %BF M %BF Equations are shown without the interaction term unless it was significant. Kg is the unit for all the variables in all the equations. P, paternal; M, maternal; BMC, bone mineral content; BMD, bone mineral density; LTM, lean tissue mass. n values were as follows: girls, 101 for DXA and 99 for TBK; mothers, 100 for DXA and 101 for TBK; fathers, 94 for DXA and 93 for TBK. of the environment was also examined in a unique way in several studies of twins (20, 21). These studies suggested that there is an environmental gene interaction affecting an individual s response to changes in energy balance induced by exercise and overfeeding. In an adoption study, the genetic influence on BMI was unaffected by several different environmental conditions that may be associated with obesity (22). The heritability estimate for %BF analyzed with DXA was 0.50 in our study of prepubertal girls and their parents. Two studies that examined %BF with hydrodensitometry in Pima Indians (10) and in Canadians enrolled in the Quebec Family Study (6) reported heritability estimates of 0.76 and 0.20, respectively. Sample sizes in these studies were larger than those in the present study and as a result, the former may reflect better point estimates of the heritabilities. However, better characterized phenotypes could lead to improved estimations of heritability. For FFM and FM, our low statistical power is most likely the reason why we failed to find significant heritability estimates. With regard to regional body composition, correlations between girls values and parental values for FM were quite low (adjusted r ), whereas those for LTM were higher (adjusted r 2 = ). This indicates that at an early age, variations in LTM trace better than do variations in FM, in part because the child has not yet accumulated large stores of excess fat. In family studies in which the offspring were adults, it was shown that for extreme BMI values (extreme obesity or leanness), skinfold-thickness measures of the biceps and triceps showed significant correlations between mother and daughter (r = 0.31 and 0.26, respectively) and father and daughter (r = 0.26 and 0.33, respectively) (23). In our study, we observed the highest correlations for FFM and TBK, rather than for FM. Among the body regions, the highest correlations between the girls and their parents were for the legs, the largest muscle region of the body. Our measures of the girl s %BF in the trunk were influenced by both the father s and mother s values. In the Quebec Family Study, a heritability estimate for total abdominal fat area (visceral and subcutaneous fat combined, measured by computed tomography) was 70%, with correlations between father and daughter and mother and daughter of 0.35 (24). Thus, these studies support the theory that both regional fat tissue and fat-free tissue in the offspring are influenced by the body composition of the parents. The higher adjusted r 2 values ( ) for regional and total BMC than for FFM and FM in our sample may indicate that bone growth and mineralization are under stronger genetic influences than are FFM or FM. The total and regional BMC of the girls were influenced by both their mothers and fathers values. Other studies have examined the genetic determinants of bone mass by studying parent-offspring relations (25, 26). The BMC of the spine, femoral neck, and midfemoral diaphysis of 8-y-old prepubertal girls was significantly correlated (r = ) with their

5 BODY COMPOSITION IN GIRLS AND THEIR PARENTS 533 mothers BMC, with 18 37% of bone traits directly determined by maternal descent (26). Thus, it appears that the results of our study agree with those of other investigations, indicating a significant relation between the bone status of parent and child. In this family study, which was restricted to girls with a %BF of 12 30%, we found that the girl s body composition at 8 9 y of age is related to their biological parents body composition. Familial resemblance of parental obesity and leanness is clearly evident in daughters at prepubertal ages. We thank the children who participated in the study, the Metabolic Research Unit staff and body-composition staff of the Baylor College of Medicine for technical assistance, and B Kertz for subject recruitment. REFERENCES 1. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE. The bodymass index of twins who have been reared apart. N Engl J Med 1990;322: Allison DB, Kaprio J, Korkeila N, Koskenvuo M, Neale MC, Hayakawa K. The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obes Relat Metab Disord 1996;20: Price RA, Cadoret RJ, Stunkard AJ, Troughton E. Genetic contributions to human fatness: an adoption study. Am J Psychiatry 1987; 144: Sorensen TIA, Holst C, Stunkard AJ. Childhood body mass index genetic and familial environmental influences assessed in a longitudinal adoption study. Int J Obes Relat Metab Disord 1992;16: Stunkard AJ, Sorensen TI, Hanis C, et al. An adoption study of human obesity. N Engl J Med 1986;314: Bouchard C, Perusse L, Leblanc C, Tremblay A, Theriault G. Inheritance of the amount and distribution of human body fat. Int J Obes 1988;12: Heller R, Garrison RJ, Havlik RJ, Feinleib M, Padgett S. Family resemblances in height and relative weight in the Framingham Heart Study. Int J Obes 1984;8: Perusse L, Leblanc C, Bouchard C. Inter-generation transmission of physical fitness in the Canadian population. Can J Sport Sci 1988; 13: Tambs K, Moum T, Eaves L, et al. Genetic and environmental contributions to the variance of the body mass index in a Norwegian sample of first- and second-degree relatives. Am J Hum Biol 1991; 3: Sakul H, Pratley R, Cardon L, Ravussin E, Mott D, Bogardus C. Familiality of physical and metabolic characteristics that predict the development of non-insulin-dependent diabetes mellitus in Pima Indians. Am J Hum Genet 1997;60: Guillaume M, Lapidus L, Beckers F, Lambert A, Bjorntorp P. Familial trends of obesity through three generations: the Belgian-Luxembourg child study. Int J Obes Relat Metab Disord 1995;19(suppl):S Najjar MF, Rowland M. Anthropometric reference data and prevalence of overweight, United States, Vital Health Stat ;238: Ellis KJ, Shypailo RJ. Whole-body potassium measurements independent of body size. Basic Life Sci 1993;60: Moore FD, Olesen KH, McMurrey JD, Parker HV, Ball MR, Boyden CM, eds. The body cell mass and its supporting environment. Philadelphia: WB Saunders Co, 1963: Forbes GB. Human body composition: growth, aging, nutrition, and activity. New York: Springer, 1987: Fomom SJ, Haschke F, Ziegler EE, Nelson SE. Body composition of reference children from birth to age 10 years. Am J Clin Nutr 1982;35: Hopper JL, Mathews JD. Extensions to multivariate normal models for pedigree analysis. Ann Hum Genet 1982;46: Lange K, Boehnke M. Extensions to pedigree analysis. IV. Covariance components models for multivariate traits. Am Med Genet 1983;14: Lange K, Weeks D, Boehnke M. Programs for Pedigree Analysis: MENDEL, FISHER, and dgene. Genet Epidemiol 1988;5: Bouchard C, Tremblay A, Despres JP, et al. The response to long-term overfeeding in identical twins. N Engl J Med 1990;322: Bouchard C, Tremblay A, Despres JP, et al. The response to exercise with constant energy intake in identical twins. Obes Res 1994;2: Sorensen TIA, Holst C, Stunkard AJ. Adoption study of environmental modifications of the genetic influences of obesity. Int J Obes Relat Metab Disord 1998;22: Price RA, Reed DR, Lee JH. Obesity related phenotypes in families selected for extreme obesity and leanness. Int J Obes Relat Metab Disord 1998;22: Perusse L, Despres JP, Lemieux S, Rice T, Rao DC, Bouchard C. Familial aggregation of abdominal visceral fat level: results from the Quebec family study. Metabolism 1996;45: Danielson ME, Cauley JA, Baker CE, et al. Familial resemblance of bone mineral density (BMD) and calcaneal ultrasound attenuation: the BMD in Mothers and Daughters Study. J Bone Miner Res 1999;14: Ferrari S, Rizzoli R, Slosman D, Bonjour JP. Familial resemblance for bone mineral mass is expressed before puberty. J Clin Endocrinol Metab 1998;83: