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December 1993, Vol 147, No. 12 >
Article | December 1993

Evidence of a Major Gene With Pleiotropic Action for a Cardiovascular Disease Risk Syndrome in Children Younger Than 14 Years FREE

David B. Allison, PhD; Stanley Heshka, PhD; Steven B. Heymsfield, MD
[+] Author Affiliations

Accepted for publication July 16, 1993.

Reprint requests to the Obesity Research Center, 411 W1 114th St, Suite 3D, New York, NY 10025 (Dr Allison).


Am J Dis Child. 1993;147(12):1298-1302. doi:10.1001/archpedi.1993.02160360040014.
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• Objective.  —To test the plausibility of the existence of a genetically based syndrome involving obesity, hypertension, and a central deposition of body fat.

Design.  —Survey of a random stratified sample of the US population.

Participants.  —Male and female children aged 13 years or younger (mean, 5.3 years; SD, 3.7 years; median, 4.0 years; range, 6 months to 13 years) were chosen from National Health and Nutrition Examination Survey II data.

Interventions.  —None.

Measurements/Main Results.  —Using multivariate commingling analysis, we evaluated the hypothesis that a major gene produces a syndrome involving the phenotypic indicators of body mass index (in kilograms per square meter), subscapular-to-triceps skinfold thickness ratio, systolic blood pressure, and diastolic blood pressure. Maximum likelihood estimation was used to test competing models. A model with three component distributions and unequal variance-covariance matrices fit significantly better than any competing model.

Conclusions.  —Our findings support the existence of a distinct cardiovascular disease risk syndrome in children and suggest that it may be the result of a major gene with pleiotropic effects.(AJDC. 1993;147:1298-1302)

REFERENCES

1 +
Bjorntorp P.  The association between obesity, adipose tissue distribution and disease . Acta Med Scand . 1987;;723 ( (suppl) ):121-134
2 +
Dustan HP.  Hypertension and obesity . Prim Care . 1991;;18:495-507.
3 +
Mahoney LT, Lauer RM, Lee J, Clarke WR.  Factors affecting tracking of coronary heart disease risk factors in children . Ann N Y Acad Sci . 1991;;623: 120-132.
4 +
Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH.  Long-term morbidity and mortality of overweight adolescents . N Engl J Med . 1992;;327: 1350-1355.
5 +
Daniels SR.  Primary hypertension in childhood and adolescence . Pediatr Ann . 1992;;21:224-234.
6 +
Julius S.  Clinical and physiological significance of borderline hypertension in youth . Pediatr Clin North Am . 1978;;25:35-45.
7 +
Rocchini AP.  Adolescent obesity and hypertension . Pediatr Clin North Am . 1993;;40:81-92.
8 +
Epstein LH.  New developments in childhood obesity . In: Stunkard AJ, Wadden TA, eds. Obesity: Theory and Therapy . New York, NY: Raven Press; 1993;:301-312.
9 +
Hunt SC, Hasstedt SJ, Kuida H, Stults BM, Hopkins PN, Williams RR.  Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins . Am J Epidemiol . 1989;;129:625-638.
10 +
Price RA, Cadoret RJ, Stunkard AJ, Troughton E.  Genetic contributions to human fatness: an adoption study . Am J Psychiatry . 1987;;144:1003-1008.
11 +
Stunkard AJ, Harris JR, Pederson NL, McClearn GE.  The body-mass index of twins who have been reared apart . N Engl J Med . 1990;;322:1483-1487.
12 +
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: 205-215.
13 +
Williams RR.  Key concepts regarding the genetics of hypertension in humans . Am J Hypertens . 1991;;4( (suppl) ):590S-593S.
14 +
Sorenson TI.  Genetic aspects of obesity . Int J Obes . 1992;;16( (suppl 2) ): 27-29.
15 +
MacLean CJ, Morton NE, Elston RC, Yee S.  Skewness in commingled distributions . Biometrics . 1976;;32:695-699.
16 +
Price RA, Ness R, Laskarzewski P.  Common major gene inheritance of extreme overweight . Hum Biol . 1990;;62:747-765.
17 +
Rice T, Borecki IB, Bouchard C, Rao DC.  Commingling analysis of regional fat distribution measures: the Quebec family study . Int J Obes . 1992;; 16:831-844.
18 +
Perusse L, Moll PP, Sing CF.  Evidence that a single gene with gender-and age-dependent effects influences systolic blood pressure determination in a population-based sample . Am J Hum Genet . 1991;;49:94-105.
19 +
Schwartz R.  New insights into the big four: obesity, diabetes, hypertension, and hyperlipidemia . Int J Obes . 1991;;15( (suppl 3) ):25.
20 +
Thompson MW, Mclnnes RR, Willard HF. Genetics in Medicine . 5th ed. Philadelphia, Pa: WB Saunders Co; 1991;.
21 +
 National Center for Health Statistics. Anthropometric reference data and prevalence of overweight, United States, 1976-1980 . In: Vital Health Statistics . Washington, DC: Public Health Service; 1987;. Public Health Service publication 87-1688; series 11; No. (238) .
22 +
Hertel RB.  Minimizing error variance introduced by missing data routines in survey analysis . Sociol Methods Res . 1976;;4:459-474.
23 +
karl JG, Heymsfield S.  Morbid obesity: definitions, epidemiology, and methodological problems . Gastroenterol Clin North Am . 1987;;16: 197-205.
24 +
Micozzi MS, Albanes D, Jones Y, Chumlea WC.  Correlations of body mass indices with weight, stature, and body composition in men and women in NHANES I and II . Am J Clin Nutr . 1986;;44:725-731.
25 +
Garrow JS, Webster J.  Quetelet's index (W/H2) as a measure of fatness . Int J Obes . 1985;;9:147-153.
26 +
National Institutes of Health.  Health implications of obesity: National Institutes of Health Consensus Development Conference statement . Ann Intern Med . 1985;;103:1073-1077.
27 +
Higgins M, Kannel W, Garrison R, Pinsky J, Stokes J.  Hazards of obesity: the Framingham experience . Acta Med Scand . 1987;;723( (suppl) ):23-36.
28 +
Fox K, Peters D, Armstrong N, Sharpe P, Bell M.  Abdominal fat deposition in 11-year-old children . Int J Obes . 1993;;17:11-16.
29 +
Jorde LB, Williams RR, Kuida H.  Factor analysis suggesting contrasting determinants for different blood pressure measurements . Hypertension . 1986;;8:243-251.
30 +
Woodward JA, Bonett DG, Brecht ML. Introduction to Linear Models and Experimental Design . New York, NY: Harcourt-Brace-Javonovich; 1990;.
31 +
Eaves LJ.  Errors of inference in the detection of major gene effects on psychological test scores . Am J Hum Genet . 1983;;35:1179-1189.
32 +
Shork NJ, Weder AB, Shork MA.  On the asymmetry of biological frequency distributions . Genet Epidemiol . 1990;;7:427-446.
33 +
McLachlan GL, Basford KE. Mixture Models . New York, NY: Marcel Dekker Inc; 1988;.
34 +
Lenzenweger MF, Moldin SO.  Discerning the latent structure of hypothetical psychosis proneness through admixture analysis . Psychiatry Res . 1990;;33:243-257.
35 +
Cloninger CR, Von Knorring L, Oreland L.  Pentametric distribution of platelet monoamine oxidase activity . Psychiatry Res . 1985;;15:133-143.
36 +
Day NE.  Estimating the components of a mixture of normal distributions . Biometrika . 1969;;56:463-474.
37 +
Milligan GW, Cooper MC.  Methodology review: clustering methods . Appl Psychol Meas . 1987;;11:329-354.
38 +
Kwon JM, Boehnke M, Burns TL, Moll PP.  Commingling and segregation analyses: comparison of results from a simulation study of a quantitative trait . Genet Epidemiol . 1990;;7:57-68.
39 +
Meehl PE.  MAXCOV-HITMAX: a taxonomic search method for loose genetic syndromes . In: Meehl PE. Psychodiagnosis: Selected Papers . New York, NY: WW Norton; 1973;:200-224.
40 +
Newman B, Selby JV, Quesenberry CP, King MC, Friedman GD, Fabsitz RR.  Nongenetic influences of obesity on other cardiovascular disease risk factors: an analysis of identical twins . Am J Public Health . 1990;;80:675-678.

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

References

1 +
Bjorntorp P.  The association between obesity, adipose tissue distribution and disease . Acta Med Scand . 1987;;723 ( (suppl) ):121-134
2 +
Dustan HP.  Hypertension and obesity . Prim Care . 1991;;18:495-507.
3 +
Mahoney LT, Lauer RM, Lee J, Clarke WR.  Factors affecting tracking of coronary heart disease risk factors in children . Ann N Y Acad Sci . 1991;;623: 120-132.
4 +
Must A, Jacques PF, Dallal GE, Bajema CJ, Dietz WH.  Long-term morbidity and mortality of overweight adolescents . N Engl J Med . 1992;;327: 1350-1355.
5 +
Daniels SR.  Primary hypertension in childhood and adolescence . Pediatr Ann . 1992;;21:224-234.
6 +
Julius S.  Clinical and physiological significance of borderline hypertension in youth . Pediatr Clin North Am . 1978;;25:35-45.
7 +
Rocchini AP.  Adolescent obesity and hypertension . Pediatr Clin North Am . 1993;;40:81-92.
8 +
Epstein LH.  New developments in childhood obesity . In: Stunkard AJ, Wadden TA, eds. Obesity: Theory and Therapy . New York, NY: Raven Press; 1993;:301-312.
9 +
Hunt SC, Hasstedt SJ, Kuida H, Stults BM, Hopkins PN, Williams RR.  Genetic heritability and common environmental components of resting and stressed blood pressures, lipids, and body mass index in Utah pedigrees and twins . Am J Epidemiol . 1989;;129:625-638.
10 +
Price RA, Cadoret RJ, Stunkard AJ, Troughton E.  Genetic contributions to human fatness: an adoption study . Am J Psychiatry . 1987;;144:1003-1008.
11 +
Stunkard AJ, Harris JR, Pederson NL, McClearn GE.  The body-mass index of twins who have been reared apart . N Engl J Med . 1990;;322:1483-1487.
12 +
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: 205-215.
13 +
Williams RR.  Key concepts regarding the genetics of hypertension in humans . Am J Hypertens . 1991;;4( (suppl) ):590S-593S.
14 +
Sorenson TI.  Genetic aspects of obesity . Int J Obes . 1992;;16( (suppl 2) ): 27-29.
15 +
MacLean CJ, Morton NE, Elston RC, Yee S.  Skewness in commingled distributions . Biometrics . 1976;;32:695-699.
16 +
Price RA, Ness R, Laskarzewski P.  Common major gene inheritance of extreme overweight . Hum Biol . 1990;;62:747-765.
17 +
Rice T, Borecki IB, Bouchard C, Rao DC.  Commingling analysis of regional fat distribution measures: the Quebec family study . Int J Obes . 1992;; 16:831-844.
18 +
Perusse L, Moll PP, Sing CF.  Evidence that a single gene with gender-and age-dependent effects influences systolic blood pressure determination in a population-based sample . Am J Hum Genet . 1991;;49:94-105.
19 +
Schwartz R.  New insights into the big four: obesity, diabetes, hypertension, and hyperlipidemia . Int J Obes . 1991;;15( (suppl 3) ):25.
20 +
Thompson MW, Mclnnes RR, Willard HF. Genetics in Medicine . 5th ed. Philadelphia, Pa: WB Saunders Co; 1991;.
21 +
 National Center for Health Statistics. Anthropometric reference data and prevalence of overweight, United States, 1976-1980 . In: Vital Health Statistics . Washington, DC: Public Health Service; 1987;. Public Health Service publication 87-1688; series 11; No. (238) .
22 +
Hertel RB.  Minimizing error variance introduced by missing data routines in survey analysis . Sociol Methods Res . 1976;;4:459-474.
23 +
karl JG, Heymsfield S.  Morbid obesity: definitions, epidemiology, and methodological problems . Gastroenterol Clin North Am . 1987;;16: 197-205.
24 +
Micozzi MS, Albanes D, Jones Y, Chumlea WC.  Correlations of body mass indices with weight, stature, and body composition in men and women in NHANES I and II . Am J Clin Nutr . 1986;;44:725-731.
25 +
Garrow JS, Webster J.  Quetelet's index (W/H2) as a measure of fatness . Int J Obes . 1985;;9:147-153.
26 +
National Institutes of Health.  Health implications of obesity: National Institutes of Health Consensus Development Conference statement . Ann Intern Med . 1985;;103:1073-1077.
27 +
Higgins M, Kannel W, Garrison R, Pinsky J, Stokes J.  Hazards of obesity: the Framingham experience . Acta Med Scand . 1987;;723( (suppl) ):23-36.
28 +
Fox K, Peters D, Armstrong N, Sharpe P, Bell M.  Abdominal fat deposition in 11-year-old children . Int J Obes . 1993;;17:11-16.
29 +
Jorde LB, Williams RR, Kuida H.  Factor analysis suggesting contrasting determinants for different blood pressure measurements . Hypertension . 1986;;8:243-251.
30 +
Woodward JA, Bonett DG, Brecht ML. Introduction to Linear Models and Experimental Design . New York, NY: Harcourt-Brace-Javonovich; 1990;.
31 +
Eaves LJ.  Errors of inference in the detection of major gene effects on psychological test scores . Am J Hum Genet . 1983;;35:1179-1189.
32 +
Shork NJ, Weder AB, Shork MA.  On the asymmetry of biological frequency distributions . Genet Epidemiol . 1990;;7:427-446.
33 +
McLachlan GL, Basford KE. Mixture Models . New York, NY: Marcel Dekker Inc; 1988;.
34 +
Lenzenweger MF, Moldin SO.  Discerning the latent structure of hypothetical psychosis proneness through admixture analysis . Psychiatry Res . 1990;;33:243-257.
35 +
Cloninger CR, Von Knorring L, Oreland L.  Pentametric distribution of platelet monoamine oxidase activity . Psychiatry Res . 1985;;15:133-143.
36 +
Day NE.  Estimating the components of a mixture of normal distributions . Biometrika . 1969;;56:463-474.
37 +
Milligan GW, Cooper MC.  Methodology review: clustering methods . Appl Psychol Meas . 1987;;11:329-354.
38 +
Kwon JM, Boehnke M, Burns TL, Moll PP.  Commingling and segregation analyses: comparison of results from a simulation study of a quantitative trait . Genet Epidemiol . 1990;;7:57-68.
39 +
Meehl PE.  MAXCOV-HITMAX: a taxonomic search method for loose genetic syndromes . In: Meehl PE. Psychodiagnosis: Selected Papers . New York, NY: WW Norton; 1973;:200-224.
40 +
Newman B, Selby JV, Quesenberry CP, King MC, Friedman GD, Fabsitz RR.  Nongenetic influences of obesity on other cardiovascular disease risk factors: an analysis of identical twins . Am J Public Health . 1990;;80:675-678.

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