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 W 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 Oskari 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; Anette P Gjesing; Torben Jørgensen; Daniel R Witte; Torben Hansen; Oluf Pedersen; 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 W 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 Oskari 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, Anette P Gjesing, Torben Jørgensen, Daniel R Witte, Torben Hansen, Oluf Pedersen, MAGIC

2060 Citations (Scopus)

Abstract

Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS 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 aSociated loci may provide new insights into human body weight regulation.

Original language	English
Journal	Nature Genetics
Volume	42
Issue number	11
Pages (from-to)	937-48
Number of pages	12
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.686
Publication status	Published - 1 Nov 2010

Keywords

Body Height
Body Mass Index
Body Size
Body Weight
Chromosome Mapping
European Continental Ancestry Group
Genetic Predisposition to Disease
Genome-Wide Association Study
Humans
Obesity
Polymorphism, Single Nucleotide

UN SDGs

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

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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., Allen, H. L., Lindgren, C. M., Luan, J., Mägi, R., Randall, J. C., Vedantam, S., Winkler, T. W., 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, TW, 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, Oskari Kilpeläinen, T, 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, Gjesing, AP, Jørgensen, T, Witte, DR, Hansen, T , Pedersen, O & MAGIC 2010, 'Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index', Nature Genetics, vol. 42, no. 11, pp. 937-48. https://doi.org/10.1038/ng.686

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

abstract = "Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and {\^ĝ}1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS 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 aSociated loci may provide new insights into human body weight regulation.",

keywords = "Body Height, Body Mass Index, Body Size, Body Weight, Chromosome Mapping, European Continental Ancestry Group, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Obesity, Polymorphism, Single Nucleotide",

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 Winkler, {Thomas W} 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 {Oskari Kilpel{\"a}inen}, Tuomas 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 Gjesing, {Anette P} and Torben J{\o}rgensen and Witte, {Daniel R} and Torben Hansen and Oluf Pedersen and MAGIC",

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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 W

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 - Oskari Kilpeläinen, Tuomas

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 - Gjesing, Anette P

AU - Jørgensen, Torben

AU - Witte, Daniel R

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - MAGIC

PY - 2010/11/1

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N2 - Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS 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 aSociated loci may provide new insights into human body weight regulation.

AB - Obesity is globaLy prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined aSociations betwEn body maS index and ĝ̂1/42.8 miLion SNPs in up to 123,865 individuals with targeted foLow up of 42 SNPs in up to 125,931 aDitional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci aSociated with body maS 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 aSociated loci may provide new insights into human body weight regulation.

KW - Body Height

KW - Body Mass Index

KW - Body Size

KW - Body Weight

KW - Chromosome Mapping

KW - European Continental Ancestry Group

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Humans

KW - Obesity

KW - Polymorphism, Single Nucleotide

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

Keywords

UN SDGs

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