title: Medical sequencing at the extremes of human body mass.
abstract: 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.
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Nadav
authors.initials: N
authors.lastname: Ahituv
authors.forename: Nihan
authors.initials: N
authors.lastname: Kavaslar
authors.forename: Wendy
authors.initials: W
authors.lastname: Schackwitz
authors.forename: Anna
authors.initials: A
authors.lastname: Ustaszewska
authors.forename: Joel
authors.initials: J
authors.lastname: Martin
authors.forename: Sybil
authors.initials: S
authors.lastname: Hebert
authors.forename: Heather
authors.initials: H
authors.lastname: Doelle
authors.forename: Baran
authors.initials: B
authors.lastname: Ersoy
authors.forename: Gregory
authors.initials: G
authors.lastname: Kryukov
authors.forename: Steffen
authors.initials: S
authors.lastname: Schmidt
authors.forename: Nir
authors.initials: N
authors.lastname: Yosef
authors.forename: Eytan
authors.initials: E
authors.lastname: Ruppin
authors.forename: Roded
authors.initials: R
authors.lastname: Sharan
authors.forename: Christian
authors.initials: C
authors.lastname: Vaisse
authors.forename: Shamil
authors.initials: S
authors.lastname: Sunyaev
authors.forename: Robert
authors.initials: R
authors.lastname: Dent
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cohen
authors.forename: Ruth
authors.initials: R
authors.lastname: McPherson
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
mesh_terms: D000328:Adult; D001835:Body Weight / Q000235:genetics*; D005091:Exons / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005796:Genes / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D044105:Receptor, Melanocortin, Type 4 / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4