The Genetics of Obesity

Claude Bouchard

• Publisher: CRC Press
• Year: 2020
• Print ISBN: 9780849348808
• eBook ISBN: 9781000141603
• Topic: Medicine
• Subtopic: Endocrinology & Metabolism

This book provides a comprehensive compilation of the evidence available regarding the role of genetic differences in the etiology of human obesities and their health and metabolic implications. It also identifies the most promising research areas, methods, and strategies for use in future efforts to understand the genetic basis of obesities and their consequences on human health. Leading researchers in their respective fields present contributed chapters on such topics as etiology and the prevalence of obesities, nongenetic determinants of obesity and fat topography, and animal models and molecular biological technology used to delineate the genetic basis of human obesities. A major portion of the book is devoted to human genetic research and clinical observations encompassing adoption studies, twin studies, family studies, single gene effects, temporal trends and etiology heterogeneity, energy intake and food preference, energy expenditure, and susceptibility to metabolic derangements in the obese state. Future directions of research in the field are covered in the book as well.

Chapter 1

GENETICS OF HUMAN OBESITIES: INTRODUCTORY NOTES

Claude Bouchard

TABLE OF CONTENTS

I.	Obesity is a Major Health Concern
II.	Historical Notes
III.	Obesity: the Phenotypes
IV.	Covariation among Phenotypes
V.	Determinants of Obesity Phenotypes A. Excess Body Fat Content B. Regional Fat Distribution Phenotypes
VI.	Stability with Age
VII.	Two Main Types of Research
References

I. OBESITY IS A MAJOR HEALTH CONCERN

The prevalence of overweight and obesity cases in contemporary industrialized nations is strikingly high. This is a fact recognized by all health authorities irrespective of political regime and national wealth. In the U.S., it has been estimated that obesity is responsible for about 5% of total health care costs.¹ Based on 1986 figures, obesity was then responsible for about $40 billion of the total health costs primarily because of the adverse effects of obesity on diabetes, cardiovascular diseases, gall-bladder disease, hypertension, and cancer.

Excess body weight is perceived as a problem by a great number of adults. Thus, as summarized recently by the National Institutes of Health Technology Assessment Conference Panel,² based on four U.S. surveys, about 33% of adult women and 20% of adult men are currently trying to lose weight. Moreover, about 25% in each sex are taking measures to maintain their present weight. Among those trying to lose weight, the time spent on a weight loss regimen during the previous year averaged about 6 months. The same surveys also indicated that diet and exercise were the most common methods used when adults attempted to lose weight, each with a frequency ranging from about 60 to 80%. Other methods were cited by about 25% and/or less of the respondents trying to reduce body weight. The Conference Panel also estimated that Americans were spending about $30 billion a year on weight loss efforts.

II. HISTORICAL NOTES

Davenport³ was among the first investigators to report data pertaining to the problem of heredity in body mass relative to stature. Using a variant of the body mass index (BMI), body weight in kilograms divided by height in centimeters squared, he studied 528 parental matings and their 926 male and 745 female offspring, about 600 of which were adults. He classified subjects into 5 classes of BMI (as specified in Table 1) in an attempt to identify Mendelian segregation from the parental to the filial generations. As suggested by the data summarized in Table 1, Davenport found some evidence for a parental influence on the BMI of adult offspring. However, all matings produced a highly variable progeny in terms of BMI classes.

Table 1. Body mass index (BMI) of adult offspring from various classes of parental mating^a

		Distribution of BMI of offspring in %
Parental mating	N offspring	VS	S	M	F	VF
VS x S	20	20	60	10	10
S x S	51	10	69	21
M x M	332	1	12	60	25	2
F x F	159		9	39	38	14
VF x VF	37			40	27	33

Note: VS = very slender (BMI: 14.0 to 18.0 in kg/m²); S = slender (BMI: 18.1 to 21.4); M = medium (BMI: 21.5 to 25.4); F = fleshy (BMI: 25.7 to 30.5); VF = very fleshy (BMI: 30.6 and above).

^a From Davenport, C. B., Body build and its inheritance, 329, 1923, as modified by Bray, G. A., The Body Weight Regulatory System: Normal and Disturbed Mechanisms,1981, 185.

Several other early studies have considered the genetics of overweight and obesity. Gurney,⁴ using a model similar to Davenport’s,³ studied the familial history of 75 women who were classified as being overweight (stout). He observed that 43% had an overweight mother, 15% had an overweight father, and 25% had both an overweight mother and an overweight father; thus 83% had either or both parents overweight. In contrast with the above, percentage figures in a nonstout control group were 30%, 2%, 6%, and 38%, respectively. Gurney also looked for Mendelian segregation among the progeny of different matings. Among 89 offspring of overweight persons, 73% were classified as being overweight and 27% as normal weight. There were 170 children of an overweight and a normal weight parent; of these, 41% were overweight and 59% were normal weight. Finally, of 176 children of matings of normal weight individuals, only 9% could be judged as being overweight. Gurney concluded that the data showed the presence of segregation, which is evidence for Mendelian inheritance of body build. Angel⁵ studied 103 adult white females who were classified as obese, with an average of 60% overweight. Familial analysis revealed that one third of the women were already fat in childhood. Studies of parental matings involving these women revealed fat-to-thin ratios of offspring similar to the data reported by Gurney.⁴ Angel observed that segregation takes place and that several genes appear to be involved.

In addition to these studies, several authors have also reported on the relationship between parents and children for obesity and overweight phenotypes.^{6, 7, 8, 9} Bray¹⁰ has reviewed eight of these studies which quite consistently demonstrated that obese children had frequently obese parents. Thus, in about 30% of the cases, both parents of obese children were obese, with a range in frequency of 6 to 43%. Of course, one can readily observe that the fit between the obese state of the children and that of the parents is variable and not very tight. Some of the reasons that can be invoked to account for this state are the small number of subjects in some studies, the various definitions of obesity that were used, the possibility that obesity may not be highly determined by the genotype, differences in lifestyle and energy balance between parents and children, and undoubtedly others.

Along these lines, the earlier data of Reynolds and Schoen¹¹ on a set of identical triplets had indicated that genes were not sufficient to make these triplets similar in terms of fat diameters measured from roentgenograms of the calf and forearm during growth. It should be noted that if interindividual differences among the triplets were surprisingly high, especially during puberty, their concordance for fatness tended, however, to increase in the post-pubertal period. This could be interpreted equally well under a genetic hypothesis or under a nutritional and energy balance model with little contribution from the genotype. Reynolds,¹² on the other hand, reported mean differences in...

Table of contents

• Cover
• Title Page
• Copyright Page
• Preface
• The Editor
• Contributors
• Table of Contents
• Chapter 1 Genetics of Human Obesities: Introductory Notes
• Chapter 2 Etiology and Prevalence of Obesity
• Chapter 3 Nongenetic Determinants of Obesity and Body Fat Topography
• Chapter 4 Overview of the Adoption Studies
• Chapter 5 Twin Studies of Human Obesity
• Chapter 6 Genetics of Obesity: Family Studies
• Chapter 7 The Case for Single Gene Effects on Human Obesity
• Chapter 8 Genetics of Obesity: Etiologic Heterogeneity and Temporal Trends
• Chapter 9 Genetics of Energy Intake and Food Preferences
• Chapter 10 Genetics of Energy Expenditure in Humans
• Chapter 11 Inherited Susceptibility to Metabolic Complications of Obesity
• Chapter 12 Animal Models of Genetic Obesity: Peripheral Tissue Changes
• Chapter 13 Identification of Genes Underlying Polygenic Obesity in Animal Models
• Chapter 14 Genetics and Molecular Biology of Adipose Cell Characteristics
• Chapter 15 Molecular Genetic Approaches to Obesity
• Chapter 16 Genetics of Obesity: Overview and Research Directions
• Index