Medical sequencing at the extremes of human body mass.
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.
Ahituv
Nadav
N
Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
Kavaslar
Nihan
N
Schackwitz
Wendy
W
Ustaszewska
Anna
A
Martin
Joel
J
Hebert
Sybil
S
Doelle
Heather
H
Ersoy
Baran
B
Kryukov
Gregory
G
Schmidt
Steffen
S
Yosef
Nir
N
Ruppin
Eytan
E
Sharan
Roded
R
Vaisse
Christian
C
Sunyaev
Shamil
S
Dent
Robert
R
Cohen
Jonathan
J
McPherson
Ruth
R
Pennacchio
Len A
LA
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
C470072:MC4R protein, human; D044105:Receptor, Melanocortin, Type 4