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

doi:10.1086/513471

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 journal › Article › peer-review

181 Scopus citations

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 language	English (US)
Pages (from-to)	779-791
Number of pages	13
Journal	American Journal of Human Genetics
Volume	80
Issue number	4
DOIs	https://doi.org/10.1086/513471
State	Published - Apr 2007

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1086/513471

Cite this

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, 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

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

@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.}",

note = "Funding Information: We thank the Joint Genome Institute{\textquoteright}s production sequencing group and Thet Naing, for technical assistance; members of the Rubin lab, for helpful comments on the manuscript; and the many subjects and their families who participated in these studies. Research was conducted at the E. O. Lawrence Berkeley National Laboratory and the Joint Genome Institute, performed under Department of Energy Contract DE-AC0378SF00098, University of California (to L.A.P.). Research performed at the Ottawa Heart Institute was supported by Heart & Stroke Foundation of Ontario grant NA5413 (to R.M.). Subject recruitment was supported in part by a grant from GlaxoSmithKline (to R.M. and R.D.). R.S. was supported by an Alon Fellowship. ",

year = "2007",

month = apr,

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.

N1 - Funding Information: We thank the Joint Genome Institute’s production sequencing group and Thet Naing, for technical assistance; members of the Rubin lab, for helpful comments on the manuscript; and the many subjects and their families who participated in these studies. Research was conducted at the E. O. Lawrence Berkeley National Laboratory and the Joint Genome Institute, performed under Department of Energy Contract DE-AC0378SF00098, University of California (to L.A.P.). Research performed at the Ottawa Heart Institute was supported by Heart & Stroke Foundation of Ontario grant NA5413 (to R.M.). Subject recruitment was supported in part by a grant from GlaxoSmithKline (to R.M. and R.D.). R.S. was supported by an Alon Fellowship.

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

C2 - 17357083

AN - SCOPUS:34147154100

SN - 0002-9297

VL - 80

SP - 779

EP - 791

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

IS - 4

ER -

Medical sequencing at the extremes of human body mass

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this