Obesity genetics: insights from the Pakistani population

Abstract

The Pakistani population is extensively diverse, indicating a genetic admixture of European and Central/West Asian migrants with indigenous South Asian gene pools. Pakistanis are organized in different ethnicities/castes based on cultural, linguistic and geographical origin. While Pakistan is facing a rapid nutritional transition, the rising prevalence of obesity is driving a growing burden of health complications and mortality. This represents a unique opportunity for the research community to study the interplay between obesogenic environmental changes and obesity predisposing genes in the time frame of one generation. This review recapitulates the ancestral origins of Pakistani population, the societal determinants of the rise in obesity and its governmental management. We describe the contribution of syndromic, monogenic non-syndromic and polygenic obesity genes identified in the Pakistani population. We then discuss the utility of gene identification approaches based on large consanguineous families and original gene × environment interaction study designs in discovering new obesity genes and causal pathways. Elucidation of the genetic basis of obesity in the Pakistani population may result in improved methods of obesity prevention and treatment globally.

A biopsychosocial approach to processes and pathways in the development of overweight and obesity in childhood: Insights from developmental theory and research

“…Research on genetic contributions to OW/OB and appetitive traits has extended to identifying the particular monogenetic and polygenetic associations, together with the mechanisms or pathways of the genetic effects . There is also evidence of different categories of genetic etiology and age‐genotype interactions in childhood (eg, lower BMI in infancy and higher BMI in later childhood) .…”

“…Although there is some literature about the development of OW/OB in children dating back to the early 1980s, it is mainly in the last 10 to 15 years that the topic has gained increased attention, partly as a basis for designing intervention and prevention programs . In relation to questions about the etiology of OW/OB, including in childhood, the predominant approach whether from reviews, individual research studies, or in the design of intervention strategies has been one based on correlates, predictors, or risks. These have covered a wide range of factors, including biological determinants (eg, genetic susceptibility and child temperament), an obesogenic environment, children's appetitive traits (eg, eating in the absence of hunger), psychosocial factors (eg, parent feeding styles and practices), ethnic group, cultural and macroenvironmental factors, as well as energy expenditure.…”

Association between -174G>C polymorphism in the IL-6 promoter region and the risk of obesity

“…Among these internal and external factors, the contribution of genetic factors has been recognized widely, but the genes involved have not been fully elucidated. [ 1 ]…”

Loss‐of‐function mutations in the melanocortin‐3 receptor gene confer risk for human obesity: A systematic review and meta‐analysis

“…In order to identify functional and phenotypic consequences of homozygous, compound heterozygous, and heterozygous carriers of rare coding LOF mutations in MC3R , resequencing a very large number of humans (ie, more than 1 million) via international genetic consortia will be required . Alternatively, resequencing the MC3R coding sequence in individuals from consanguineous families may increase the likelihood of identifying a homozygous carrier of LOF mutation …”

“…46 Alternatively, resequencing the MC3R coding sequence in individuals from consanguineous families may increase the likelihood of identifying a homozygous carrier of LOF mutation. 49 Though rare LOF mutations in MC3R mutations may not necessarily lead to obesity, it is important to note that the combined effect of carrying one or more of these variants may significantly elevate obesity risk. Indeed, when polygenic variants are studied together, patients with disease risk similar to those of carriers of monogenic mutations has been observed.…”