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Investigation of Mendelian forms of obesity holds out the prospect of personalized medicine
Author(s) -
Blakemore Alexandra I. F.,
Froguel Philippe
Publication year - 2010
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1111/j.1749-6632.2010.05880.x
Subject(s) - mendelian inheritance , obesity , single nucleotide polymorphism , biology , genetics , snp , bioinformatics , medicine , gene , endocrinology , genotype
Mendelian forms of obesity are already known to account for approximately 5% of the severely obese but are currently underinvestigated. In contrast, there has been much recent concentration on genome‐wide single nucleotide polymorphism (SNP) associations in obesity, with particular emphasis given to the role of the fat mass and obesity associated (FTO) gene. Unfortunately, despite the enormous resources devoted to this work, none of the SNP markers in the ∼30 genes discovered to have associations with common obesity have meaningful predictive power. This is very different from the situation for Mendelian obesity, where mutations have very clear effects on phenotype. Study of Mendelian obesity has also added significantly to our understanding of mechanisms of appetite regulation, with all known causative genes being active in the brain and most forming part of the leptin–melanocortin signaling pathway. Investigation of genomic structural variation has also recently revealed deletions causing obesity, sometimes with concomitant neurocognitive dysfunction. Advances in next‐generation sequencing are expected to uncover additional highly penetrant causes of obesity. Screening for Mendelian forms of obesity is rarely carried out but holds considerable promise for improved clinical care of these high‐risk patients.