| Medical Sequencing at the Extremes of Human Body Mass REPORT (2008) | |||||||||||||
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| Body weight is a quantitative trait with significant heritability in humans. To identify potential genetic contributors to this phenotype, we resequenced the coding exons and splice junctions of 58 genes in 379 obese and 378 lean individuals. Our 96-Mb survey included 21 genes associated with monogenic forms of obesity in humans or mice, as well as 37 genes that function in body weight–related pathways. We found that the monogenic obesity–associated gene group was enriched for rare nonsynonymous variants unique to the obese population compared with the lean population. In addition, computational analysis predicted a greater fraction of deleterious variants within the obese cohort. Together, these data suggest that multiple rare alleles contribute to obesity in the population and provide a medical sequencing-based approach to detect them. Obesity is reaching epidemic proportions in developed countries and represents a significant risk factor for hypertension, heart disease, diabetes, and dyslipidemia. 1 Although the growing prevalence of obesity in the population is thought to be caused by increasing caloric intake and declining energy expenditure, 2 individual susceptibility to obesity is strongly influenced by heredity. Twin, | |||||||||||||
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