Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Elizabeth K. Speliotes; Cristen J. Willer; Sonja I. Berndt; Keri L. Monda; Gudmar Thorleifsson; Anne U. Jackson; Hana  Lango Allen; Cecilia M. Lindgren; Jian'an Luan; Reedik Maegi; Joshua C. Randall; Sailaja Vedantam; Thomas W. Winkler; Lu Qi; Tsegaselassie Workalemahu; Iris M. Heid; Valgerdur Steinthorsdottir; Heather M. Stringham; Michael N. Weedon; Eleanor Wheeler; Andrew R. Wood; Teresa Ferreira; Robert J. Weyant; Ayellet V. Segre; Karol Estrada; Liming Liang; James Nemesh; Ju-Hyun Park; Stefan Gustafsson; Tuomas O. Kilpelaenen; Jian Yang; Nabila Bouatia-Naji; Tonu Esko; Mary F. Feitosa; Zoltan Kutalik; Massimo Mangino; Soumya Raychaudhuri; Andre Scherag; Albert Vernon Smith; Ryan Welch; Jing Hua Zhao; Katja K. Aben; Devin M. Absher; Najaf Amin; Anna L. Dixon; Eva Fisher; Nicole L. Glazer; Michael E. Goddard; Nancy L. Heard-Costa; John Connell; MAGIC

doi:10.1038/ng.686

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Elizabeth K. Speliotes
, Cristen J. Willer
, Sonja I. Berndt
, Keri L. Monda
, Gudmar Thorleifsson
, Anne U. Jackson
, Hana Lango Allen
, Cecilia M. Lindgren
, Jian'an Luan
, Reedik Maegi
, Joshua C. Randall
, Sailaja Vedantam
, Thomas W. Winkler
, Lu Qi
, Tsegaselassie Workalemahu
, Iris M. Heid
, Valgerdur Steinthorsdottir
, Heather M. Stringham
, Michael N. Weedon
, Eleanor Wheeler

Andrew R. Wood, Teresa Ferreira, Robert J. Weyant, Ayellet V. Segre, Karol Estrada, Liming Liang, James Nemesh, Ju-Hyun Park, Stefan Gustafsson, Tuomas O. Kilpelaenen, Jian Yang, Nabila Bouatia-Naji, Tonu Esko, Mary F. Feitosa, Zoltan Kutalik, Massimo Mangino, Soumya Raychaudhuri, Andre Scherag, Albert Vernon Smith, Ryan Welch, Jing Hua Zhao, Katja K. Aben, Devin M. Absher, Najaf Amin, Anna L. Dixon, Eva Fisher, Nicole L. Glazer, Michael E. Goddard, Nancy L. Heard-Costa, John Connell, MAGIC

Research output: Contribution to journal › Article › peer-review

2511 Citations (Scopus)

Abstract

Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

Original language	English
Pages (from-to)	937-U53
Number of pages	14
Journal	Nature Genetics
Volume	42
Issue number	11
DOIs	https://doi.org/10.1038/ng.686
Publication status	Published - Nov 2010

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

GENOME-WIDE ASSOCIATION
GASTRIC-INHIBITORY POLYPEPTIDE
MELANOCORTIN-4 RECEPTOR GENE
GLUCOSE-HOMEOSTASIS
COMMON VARIANTS
ADULT OBESITY
EARLY-ONSET
FTO GENE
FAT MASS
RISK

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10.1038/ng.686

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Speliotes, E. K., Willer, C. J., Berndt, S. I., Monda, K. L., Thorleifsson, G., Jackson, A. U., Lango Allen, H., Lindgren, C. M., Luan, J., Maegi, R., Randall, J. C., Vedantam, S., Winkler, T. W., Qi, L., Workalemahu, T., Heid, I. M., Steinthorsdottir, V., Stringham, H. M., Weedon, M. N., ... MAGIC (2010). Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nature Genetics, 42(11), 937-U53. https://doi.org/10.1038/ng.686

@article{c232adce766c4a5cb38e8b4562f33605,

title = "Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index",

abstract = "Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.",

keywords = "GENOME-WIDE ASSOCIATION, GASTRIC-INHIBITORY POLYPEPTIDE, MELANOCORTIN-4 RECEPTOR GENE, GLUCOSE-HOMEOSTASIS, COMMON VARIANTS, ADULT OBESITY, EARLY-ONSET, FTO GENE, FAT MASS, RISK",

author = "Speliotes, \{Elizabeth K.\} and Willer, \{Cristen J.\} and Berndt, \{Sonja I.\} and Monda, \{Keri L.\} and Gudmar Thorleifsson and Jackson, \{Anne U.\} and \{Lango Allen\}, Hana and Lindgren, \{Cecilia M.\} and Jian'an Luan and Reedik Maegi and Randall, \{Joshua C.\} and Sailaja Vedantam and Winkler, \{Thomas W.\} and Lu Qi and Tsegaselassie Workalemahu and Heid, \{Iris M.\} and Valgerdur Steinthorsdottir and Stringham, \{Heather M.\} and Weedon, \{Michael N.\} and Eleanor Wheeler and Wood, \{Andrew R.\} and Teresa Ferreira and Weyant, \{Robert J.\} and Segre, \{Ayellet V.\} and Karol Estrada and Liming Liang and James Nemesh and Ju-Hyun Park and Stefan Gustafsson and Kilpelaenen, \{Tuomas O.\} and Jian Yang and Nabila Bouatia-Naji and Tonu Esko and Feitosa, \{Mary F.\} and Zoltan Kutalik and Massimo Mangino and Soumya Raychaudhuri and Andre Scherag and Smith, \{Albert Vernon\} and Ryan Welch and Zhao, \{Jing Hua\} and Aben, \{Katja K.\} and Absher, \{Devin M.\} and Najaf Amin and Dixon, \{Anna L.\} and Eva Fisher and Glazer, \{Nicole L.\} and Goddard, \{Michael E.\} and Heard-Costa, \{Nancy L.\} and John Connell and MAGIC",

year = "2010",

month = nov,

doi = "10.1038/ng.686",

language = "English",

volume = "42",

pages = "937--U53",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

}

Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Lango Allen, H, Lindgren, CM, Luan, J, Maegi, R, Randall, JC, Vedantam, S, Winkler, TW, Qi, L, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segre, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpelaenen, TO, Yang, J, Bouatia-Naji, N, Esko, T, Feitosa, MF, Kutalik, Z, Mangino, M, Raychaudhuri, S, Scherag, A, Smith, AV, Welch, R, Zhao, JH, Aben, KK, Absher, DM, Amin, N, Dixon, AL, Fisher, E, Glazer, NL, Goddard, ME, Heard-Costa, NL, Connell, J & MAGIC 2010, 'Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index', Nature Genetics, vol. 42, no. 11, pp. 937-U53. https://doi.org/10.1038/ng.686

TY - JOUR

T1 - Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

AU - Speliotes, Elizabeth K.

AU - Willer, Cristen J.

AU - Berndt, Sonja I.

AU - Monda, Keri L.

AU - Thorleifsson, Gudmar

AU - Jackson, Anne U.

AU - Lango Allen, Hana

AU - Lindgren, Cecilia M.

AU - Luan, Jian'an

AU - Maegi, Reedik

AU - Randall, Joshua C.

AU - Vedantam, Sailaja

AU - Winkler, Thomas W.

AU - Qi, Lu

AU - Workalemahu, Tsegaselassie

AU - Heid, Iris M.

AU - Steinthorsdottir, Valgerdur

AU - Stringham, Heather M.

AU - Weedon, Michael N.

AU - Wheeler, Eleanor

AU - Wood, Andrew R.

AU - Ferreira, Teresa

AU - Weyant, Robert J.

AU - Segre, Ayellet V.

AU - Estrada, Karol

AU - Liang, Liming

AU - Nemesh, James

AU - Park, Ju-Hyun

AU - Gustafsson, Stefan

AU - Kilpelaenen, Tuomas O.

AU - Yang, Jian

AU - Bouatia-Naji, Nabila

AU - Esko, Tonu

AU - Feitosa, Mary F.

AU - Kutalik, Zoltan

AU - Mangino, Massimo

AU - Raychaudhuri, Soumya

AU - Scherag, Andre

AU - Smith, Albert Vernon

AU - Welch, Ryan

AU - Zhao, Jing Hua

AU - Aben, Katja K.

AU - Absher, Devin M.

AU - Amin, Najaf

AU - Dixon, Anna L.

AU - Fisher, Eva

AU - Glazer, Nicole L.

AU - Goddard, Michael E.

AU - Heard-Costa, Nancy L.

AU - Connell, John

AU - MAGIC

PY - 2010/11

Y1 - 2010/11

N2 - Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

AB - Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.

KW - GENOME-WIDE ASSOCIATION

KW - GASTRIC-INHIBITORY POLYPEPTIDE

KW - MELANOCORTIN-4 RECEPTOR GENE

KW - GLUCOSE-HOMEOSTASIS

KW - COMMON VARIANTS

KW - ADULT OBESITY

KW - EARLY-ONSET

KW - FTO GENE

KW - FAT MASS

KW - RISK

U2 - 10.1038/ng.686

DO - 10.1038/ng.686

M3 - Article

C2 - 20935630

SN - 1061-4036

VL - 42

SP - 937-U53

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index

Abstract

UN SDGs

Keywords

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