Medical sequencing at the extremes of human body mass

Nadav Ahituv, Nihan Kavaslar, Wendy Schackwitz, Anna Ustaszewska, Joel Martin, Sybil Hébert, Heather Doelle, Baran Ersoy, Gregory Kryukov, Steffen Schmidt, Nir Yosef, Eytan Ruppin, Roded Sharan, Christian Vaisse, Shamil Sunyaev, Robert Dent, Jonathan Cohen, Ruth McPherson, Len A. Pennacchio

Research output: Contribution to journalArticle

165 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)779-791
Number of pages13
JournalAmerican Journal of Human Genetics
Volume80
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Human Body
Obesity
Genes
Body Weight
Population
Exons
Alleles
Phenotype

ASJC Scopus subject areas

  • Genetics

Cite this

Ahituv, N., Kavaslar, N., Schackwitz, W., Ustaszewska, A., Martin, J., Hébert, S., ... Pennacchio, L. A. (2007). Medical sequencing at the extremes of human body mass. American Journal of Human Genetics, 80(4), 779-791. https://doi.org/10.1086/513471

Medical sequencing at the extremes of human body mass. / Ahituv, Nadav; Kavaslar, Nihan; Schackwitz, Wendy; Ustaszewska, Anna; Martin, Joel; Hébert, Sybil; Doelle, Heather; Ersoy, Baran; Kryukov, Gregory; Schmidt, Steffen; Yosef, Nir; Ruppin, Eytan; Sharan, Roded; Vaisse, Christian; Sunyaev, Shamil; Dent, Robert; Cohen, Jonathan; McPherson, Ruth; Pennacchio, Len A.

In: American Journal of Human Genetics, Vol. 80, No. 4, 04.2007, p. 779-791.

Research output: Contribution to journalArticle

Ahituv, N, Kavaslar, N, Schackwitz, W, Ustaszewska, A, Martin, J, Hébert, S, Doelle, H, Ersoy, B, Kryukov, G, Schmidt, S, Yosef, N, Ruppin, E, Sharan, R, Vaisse, C, Sunyaev, S, Dent, R, Cohen, J, McPherson, R & Pennacchio, LA 2007, 'Medical sequencing at the extremes of human body mass', American Journal of Human Genetics, vol. 80, no. 4, pp. 779-791. https://doi.org/10.1086/513471
Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Martin J, Hébert S et al. Medical sequencing at the extremes of human body mass. American Journal of Human Genetics. 2007 Apr;80(4):779-791. https://doi.org/10.1086/513471
Ahituv, Nadav ; Kavaslar, Nihan ; Schackwitz, Wendy ; Ustaszewska, Anna ; Martin, Joel ; Hébert, Sybil ; Doelle, Heather ; Ersoy, Baran ; Kryukov, Gregory ; Schmidt, Steffen ; Yosef, Nir ; Ruppin, Eytan ; Sharan, Roded ; Vaisse, Christian ; Sunyaev, Shamil ; Dent, Robert ; Cohen, Jonathan ; McPherson, Ruth ; Pennacchio, Len A. / Medical sequencing at the extremes of human body mass. In: American Journal of Human Genetics. 2007 ; Vol. 80, No. 4. pp. 779-791.
@article{bd46b330ff0149238ed32c9ba5a7a519,
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.",
author = "Nadav Ahituv and Nihan Kavaslar and Wendy Schackwitz and Anna Ustaszewska and Joel Martin and Sybil H{\'e}bert and Heather Doelle and Baran Ersoy and Gregory Kryukov and Steffen Schmidt and Nir Yosef and Eytan Ruppin and Roded Sharan and Christian Vaisse and Shamil Sunyaev and Robert Dent and Jonathan Cohen and Ruth McPherson and Pennacchio, {Len A.}",
year = "2007",
month = "4",
doi = "10.1086/513471",
language = "English (US)",
volume = "80",
pages = "779--791",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "4",

}

TY - JOUR

T1 - Medical sequencing at the extremes of human body mass

AU - Ahituv, Nadav

AU - Kavaslar, Nihan

AU - Schackwitz, Wendy

AU - Ustaszewska, Anna

AU - Martin, Joel

AU - Hébert, Sybil

AU - Doelle, Heather

AU - Ersoy, Baran

AU - Kryukov, Gregory

AU - Schmidt, Steffen

AU - Yosef, Nir

AU - Ruppin, Eytan

AU - Sharan, Roded

AU - Vaisse, Christian

AU - Sunyaev, Shamil

AU - Dent, Robert

AU - Cohen, Jonathan

AU - McPherson, Ruth

AU - Pennacchio, Len A.

PY - 2007/4

Y1 - 2007/4

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=34147154100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34147154100&partnerID=8YFLogxK

U2 - 10.1086/513471

DO - 10.1086/513471

M3 - Article

VL - 80

SP - 779

EP - 791

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 4

ER -