Genetics of Obesity Syndromes

Monogenic Obesity Panel
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Contents:

  • Condition Description
  • Genetics of obesity
  • Other Factors in Weight Gain | Healthy Weight | CDC
  • Other Factors in Weight Gain
  • Learned Behaviors and Habits
  • chapter and author info

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    Condition Description

    Front Horm Res. ; doi: / Genetic obesity syndromes. Goldstone AP(1), Beales PL. Author information: (1)MRC Clinical. The diagnosis of a genetic obesity syndrome can provide information that has value for the patient and their family and may help them deal with.

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    Genetics of obesity

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    Genetic Basis Of Obesity

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    Other Factors in Weight Gain | Healthy Weight | CDC

    Caring for Others. A spectrum of rare disorders Although rare genetic disorders of obesity have common features such as insatiable hunger , each disorder has a distinct clinical phenotype. Options for diagnosing suspected cases Advancements in genetic screening for confirming suspected rare genetic disorders of obesity have only recently become available to clinicians. Sign Up. Sign up to receive more information about rare genetic disorders of obesity.

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    Show References. Pediatric obesity—assessment, treatment, and prevention: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. GWLS aim to identify chromosomal regions harboring genes for a specific phenotype by making use of the linkage data. Approximately highly polymorphic markers at 10 cM intervals are mapped followed by fine mapping of regions under linkage peaks. A meta-analysis of 37 genome-wide linkage scans showed no evidence of significant linkage to any of the chromosomal regions studied. A haplotype map of Human Genome.

    Other Factors in Weight Gain

    A second generation human haplotype map of over 3. GWAS are a hypothesis-generating, agnostic method in which a large number of genetic markers SNPs spanning the entire genome are interrogated for their association with the phenotype of interest. The first gene reported to be associated with obesity was the insulin-induced gene 2 INSIG2 which was from the Framingham Heart study that involved case—control and family studies of different ethnic groups.

    This was followed by the identification of FTO gene which was unequivocally associated with obesity. But after adjustment for BMI, the association was lost, and this was replicated consistently in several populations confirming the association of this SNP with common obesity in several populations such as European, Asian, and African.

    More than 60 polymorphisms of this gene have been significantly associated with obesity and its related traits. It is however important to recognize that FTO is consistently associated with BMI, waist and hip circumference in all the analyses of heritability. Since , obesity and related traits GWAS have been performed in several waves, with larger sample size in each subsequent wave Table 2.

    As of today, there are five waves of discovery for BMI. Ever since the discovery of FTO as an obesity susceptibility loci, it has been replicated in many populations to investigate its association with BMI and related traits. Variations in this gene have been associated with risk of overweight and obesity and traits related to them. A meta-analysis of 15 cohorts was combined, and replication was followed in these samples. Subsequently, a meta-analysis was performed. The third wave saw a total of 12 loci associated with BMI. To increase the power of the study and to find alleles with low frequency, the GIANT consortium increased the sample size.

    Eighteen additional novel loci associated with BMI were discovered. At this stage, a total of 32 loci associated with BMI were identified. However, the combined effect of the 32 loci is only 1. Hence, predicting obesity using the risk alleles of these BMI loci is not accurate. In the fifth wave, besides confirming all the 32 BMI-associated loci, 7 new loci were identified which explained an additional 0.

    Two waves of GWAS for abdominal obesity have been performed.

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    In the second wave, 14 loci were discovered which were more specific to abdominal obesity; 7 of these loci were significantly more pronounced in women given the sex-specific distributions of WHR. For adiposity, body fat percentage is a more accurate measurement than BMI which does little to differentiate lean and fat mass. A GWAS combining 15 cohorts and including 36, individuals 83 was performed.

    The one near IRS1 locus was found to be associated with a number of metabolic traits, including insulin resistance, T2DM, and cardiovascular disease. Individuals with extreme obese phenotypes are likely to present more common risk alleles.

    Regulation of body composition

    Most of the GWAS has been performed in the population of White European descent except for one study which screened a South Asian population at a discovery stage. Studies across such loci in different populations might indicate more precisely, where the causal variant or gene might be located. Of all the gene loci, FTO locus has been replicated consistently across populations of different ethnic backgrounds. However, risk allele frequency varies substantially between these populations.

    While the risk allele frequency is higher in Asian Indians, the effect size is similar to White Europeans.

    Learned Behaviors and Habits

    The BMI meta-analyses resulted in the identification of 97 genome-wide significant loci. This could be attributed to a number of reasons, such as lack of coverage of rare variants, genetic heterogeneity across the population, gene—gene and gene—environment interactions, and epigenetic factors. Some of the important loci associated with different measures of obesity are given in Table 3. Although significant developments have been made over the past 10 years in the genetic basis of human obesity, much remains to be done in dissecting out the entire heritability of this disorder.

    Additional genetic factors need to be identified to explain the greater proportion of the disease.

    chapter and author info

    The assertion of the importance of genetic factors has, until recently, largely been based on twin and adoption studies. Photos: Hidden medical causes of weight gain. Add Another Author. Learn more. Email or Customer ID. In a study done in southwestern American Indians, Ravussin et al. The term eating disorders refers to a group of medical problems that have an unhealthy focus on eating, dieting, losing or gaining weight, and body image.

    There exist certain limitations in genetic approaches in unraveling the complexity of obesity.