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 Mägi; Joshua C Randall; Sailaja Vedantam; Thomas Winkler; Qi Lu; 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 Segrè; Karol Estrada; Liming Liang; James Nemesh; Ju-Hyun Park; Stefan Gustafsson; Tuomas O Kilpeläinen; Jian Yang; Nabila Bouatia-Naji; Tõnu Esko; Mary F Feitosa; Zoltán 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; Torben Jørgensen; 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 Mägi, Joshua C Randall, Sailaja Vedantam, Thomas Winkler, Qi Lu, Tsegaselassie Workalemahu, Iris M Heid, Valgerdur Steinthorsdottir, Heather M Stringham, Michael N Weedon, Eleanor WheelerAndrew R Wood, Teresa Ferreira, Robert J Weyant, Ayellet V Segrè, Karol Estrada, Liming Liang, James Nemesh, Ju-Hyun Park, Stefan Gustafsson, Tuomas O Kilpeläinen, Jian Yang, Nabila Bouatia-Naji, Tõnu Esko, Mary F Feitosa, Zoltán 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, Torben Jørgensen, MAGIC

2483 Citationer (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 ∼ 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 × 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.

Originalsprog	Engelsk
Tidsskrift	Nature Genetics
Vol/bind	42
Udgave nummer	11
Sider (fra-til)	937-48
Antal sider	12
ISSN	1061-4036
DOI	https://doi.org/10.1038/ng.686
Status	Udgivet - 1 nov. 2010

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Speliotes, E. K., Willer, C. J., Berndt, S. I., Monda, K. L., Thorleifsson, G., Jackson, A. U., Allen, H. L., Lindgren, C. M., Luan, J., Mägi, R., Randall, J. C., Vedantam, S., Winkler, T., Lu, Q., 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), 937-48. https://doi.org/10.1038/ng.686

Speliotes, EK, Willer, CJ, Berndt, SI, Monda, KL, Thorleifsson, G, Jackson, AU, Allen, HL, Lindgren, CM, Luan, J, Mägi, R, Randall, JC, Vedantam, S, Winkler, T, Lu, Q, Workalemahu, T, Heid, IM, Steinthorsdottir, V, Stringham, HM, Weedon, MN, Wheeler, E, Wood, AR, Ferreira, T, Weyant, RJ, Segrè, AV, Estrada, K, Liang, L, Nemesh, J, Park, J-H, Gustafsson, S, Kilpeläinen, 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, Jørgensen, T & MAGIC 2010, 'Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index', Nature Genetics, bind 42, nr. 11, s. 937-48. https://doi.org/10.1038/ng.686

@article{a1c7539070ba47d9a5ea8f7c0af8ab5a,

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 ∼ 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 × 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.",

author = "Speliotes, {Elizabeth K} and Willer, {Cristen J} and Berndt, {Sonja I} and Monda, {Keri L} and Gudmar Thorleifsson and Jackson, {Anne U} and Allen, {Hana Lango} and Lindgren, {Cecilia M} and Jian'an Luan and Reedik M{\"a}gi and Randall, {Joshua C} and Sailaja Vedantam and Thomas Winkler and Qi Lu 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 Segr{\`e}, {Ayellet V} and Karol Estrada and Liming Liang and James Nemesh and Ju-Hyun Park and Stefan Gustafsson and Kilpel{\"a}inen, {Tuomas O} and Jian Yang and Nabila Bouatia-Naji and T{\~o}nu Esko and Feitosa, {Mary F} and Zolt{\'a}n 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 Torben J{\o}rgensen and MAGIC",

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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 - Allen, Hana Lango

AU - Lindgren, Cecilia M

AU - Luan, Jian'an

AU - Mägi, Reedik

AU - Randall, Joshua C

AU - Vedantam, Sailaja

AU - Winkler, Thomas

AU - Lu, Qi

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 - Segrè, Ayellet V

AU - Estrada, Karol

AU - Liang, Liming

AU - Nemesh, James

AU - Park, Ju-Hyun

AU - Gustafsson, Stefan

AU - Kilpeläinen, Tuomas O

AU - Yang, Jian

AU - Bouatia-Naji, Nabila

AU - Esko, Tõnu

AU - Feitosa, Mary F

AU - Kutalik, Zoltán

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 - Jørgensen, Torben

AU - MAGIC

PY - 2010/11/1

Y1 - 2010/11/1

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 ∼ 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 × 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 ∼ 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 × 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.

U2 - 10.1038/ng.686

DO - 10.1038/ng.686

M3 - Journal article

C2 - 20935630

SN - 1061-4036

VL - 42

SP - 937

EP - 948

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

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