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Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. / Oskari Kilpeläinen, Tuomas; Zillikens, M Carola; Stančákova, Alena; Finucane, Francis M; Ried, Janina S; Langenberg, Claudia; Zhang, Weihua; Beckmann, Jacques S; Luan, Jian'an; Vandenput, Liesbeth; Styrkarsdottir, Unnur; Zhou, Yanhua; Smith, Albert Vernon; Zhao, Jing-Hua; Amin, Najaf; Vedantam, Sailaja; Shin, So-Youn; Haritunians, Talin; Fu, Mao; Feitosa, Mary F; Kumari, Meena; Halldorsson, Bjarni V; Tikkanen, Emmi; Mangino, Massimo; Hayward, Caroline; Song, Ci; Arnold, Alice M; Aulchenko, Yurii S; Oostra, Ben A; Campbell, Harry; Cupples, L Adrienne; Davis, Kathryn E; Döring, Angela; Eiriksdottir, Gudny; Estrada, Karol; Fernández-Real, José Manuel; Garcia, Melissa; Gieger, Christian; Glazer, Nicole L; Guiducci, Candace; Hofman, Albert; Humphries, Steve E; Isomaa, Bo; Jacobs, Leonie C; Jula, Antti; Karasik, David; Karlsson, Magnus K; Khaw, Kay-Tee; Kim, Lauren J; Kivimäki, Mika; Klopp, Norman; Kühnel, Brigitte; Kuusisto, Johanna; Liu, Yongmei; Ljunggren, Osten; Lorentzon, Mattias; Luben, Robert N; McKnight, Barbara; Mellström, Dan; Mitchell, Braxton D; Mooser, Vincent; Moreno, José Maria; Männistö, Satu; O'Connell, Jeffery R; Pascoe, Laura; Peltonen, Leena; Peral, Belén; Perola, Markus; Psaty, Bruce M; Salomaa, Veikko; Savage, David B; Semple, Robert K; Skaric-Juric, Tatjana; Sigurdsson, Gunnar; Song, Kijoung S; Spector, Timothy D; Syvänen, Ann-Christine; Talmud, Philippa J; Thorleifsson, Gudmar; Thorsteinsdottir, Unnur; Uitterlinden, André G; van Duijn, Cornelia M; Vidal-Puig, Antonio; Wild, Sarah H; Wright, Alan F; Clegg, Deborah J; Schadt, Eric; Wilson, James; Rudan, Igor; Ripatti, Samuli; Borecki, Ingrid B; Shuldiner, Alan R; Ingelsson, Erik; Jansson, John-Olov; Kaplan, Robert C; Gudnason, Vilmundur; Harris, Tamara B; Groop, Leif; Kiel, Douglas P; Rivadeneira, Fernando; Walker, Mark; Barroso, Inês; Vollenweider, Peter; Waeber, Gérard; Chambers, John C; Kooner, Jaspal S; Soranzo, Nicole; Hirschhorn, Joel N; Stefansson, Kari; Wichmann, H-Erich; Ohlsson, Claes; O'Rahilly, Stephen; Wareham, Nicholas J; Speliotes, Elizabeth K; Fox, Caroline S; Laakso, Markku; Loos, Ruth J F.
In:
Nature Genetics, Vol. 43, No. 8, 08.2011, p. 753-60.
Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
Oskari Kilpeläinen, T, Zillikens, MC, Stančákova, A, Finucane, FM, Ried, JS, Langenberg, C, Zhang, W, Beckmann, JS, Luan, J, Vandenput, L, Styrkarsdottir, U, Zhou, Y, Smith, AV, Zhao, J-H, Amin, N, Vedantam, S, Shin, S-Y, Haritunians, T, Fu, M, Feitosa, MF, Kumari, M, Halldorsson, BV, Tikkanen, E, Mangino, M, Hayward, C, Song, C, Arnold, AM, Aulchenko, YS, Oostra, BA, Campbell, H, Cupples, LA, Davis, KE, Döring, A, Eiriksdottir, G, Estrada, K, Fernández-Real, JM, Garcia, M, Gieger, C, Glazer, NL, Guiducci, C, Hofman, A, Humphries, SE, Isomaa, B, Jacobs, LC, Jula, A, Karasik, D, Karlsson, MK, Khaw, K-T, Kim, LJ, Kivimäki, M, Klopp, N, Kühnel, B, Kuusisto, J, Liu, Y, Ljunggren, O, Lorentzon, M, Luben, RN, McKnight, B, Mellström, D, Mitchell, BD, Mooser, V, Moreno, JM, Männistö, S, O'Connell, JR, Pascoe, L, Peltonen, L, Peral, B, Perola, M, Psaty, BM, Salomaa, V, Savage, DB, Semple, RK, Skaric-Juric, T, Sigurdsson, G, Song, KS, Spector, TD, Syvänen, A-C, Talmud, PJ, Thorleifsson, G, Thorsteinsdottir, U, Uitterlinden, AG, van Duijn, CM, Vidal-Puig, A, Wild, SH, Wright, AF, Clegg, DJ, Schadt, E, Wilson, J, Rudan, I, Ripatti, S, Borecki, IB, Shuldiner, AR, Ingelsson, E, Jansson, J-O, Kaplan, RC, Gudnason, V, Harris, TB, Groop, L, Kiel, DP, Rivadeneira, F, Walker, M, Barroso, I, Vollenweider, P, Waeber, G, Chambers, JC, Kooner, JS, Soranzo, N, Hirschhorn, JN, Stefansson, K, Wichmann, H-E, Ohlsson, C, O'Rahilly, S, Wareham, NJ, Speliotes, EK, Fox, CS, Laakso, M & Loos, RJF 2011, '
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile',
Nature Genetics, vol. 43, no. 8, pp. 753-60.
https://doi.org/10.1038/ng.866
APA
Oskari Kilpeläinen, T., Zillikens, M. C., Stančákova, A., Finucane, F. M., Ried, J. S., Langenberg, C., Zhang, W., Beckmann, J. S., Luan, J., Vandenput, L., Styrkarsdottir, U., Zhou, Y., Smith, A. V., Zhao, J-H., Amin, N., Vedantam, S., Shin, S-Y., Haritunians, T., Fu, M., ... Loos, R. J. F. (2011).
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
Nature Genetics,
43(8), 753-60.
https://doi.org/10.1038/ng.866
Vancouver
Oskari Kilpeläinen T, Zillikens MC, Stančákova A, Finucane FM, Ried JS, Langenberg C et al.
Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile.
Nature Genetics. 2011 Aug;43(8):753-60.
https://doi.org/10.1038/ng.866
Author
Oskari Kilpeläinen, Tuomas ; Zillikens, M Carola ; Stančákova, Alena ; Finucane, Francis M ; Ried, Janina S ; Langenberg, Claudia ; Zhang, Weihua ; Beckmann, Jacques S ; Luan, Jian'an ; Vandenput, Liesbeth ; Styrkarsdottir, Unnur ; Zhou, Yanhua ; Smith, Albert Vernon ; Zhao, Jing-Hua ; Amin, Najaf ; Vedantam, Sailaja ; Shin, So-Youn ; Haritunians, Talin ; Fu, Mao ; Feitosa, Mary F ; Kumari, Meena ; Halldorsson, Bjarni V ; Tikkanen, Emmi ; Mangino, Massimo ; Hayward, Caroline ; Song, Ci ; Arnold, Alice M ; Aulchenko, Yurii S ; Oostra, Ben A ; Campbell, Harry ; Cupples, L Adrienne ; Davis, Kathryn E ; Döring, Angela ; Eiriksdottir, Gudny ; Estrada, Karol ; Fernández-Real, José Manuel ; Garcia, Melissa ; Gieger, Christian ; Glazer, Nicole L ; Guiducci, Candace ; Hofman, Albert ; Humphries, Steve E ; Isomaa, Bo ; Jacobs, Leonie C ; Jula, Antti ; Karasik, David ; Karlsson, Magnus K ; Khaw, Kay-Tee ; Kim, Lauren J ; Kivimäki, Mika ; Klopp, Norman ; Kühnel, Brigitte ; Kuusisto, Johanna ; Liu, Yongmei ; Ljunggren, Osten ; Lorentzon, Mattias ; Luben, Robert N ; McKnight, Barbara ; Mellström, Dan ; Mitchell, Braxton D ; Mooser, Vincent ; Moreno, José Maria ; Männistö, Satu ; O'Connell, Jeffery R ; Pascoe, Laura ; Peltonen, Leena ; Peral, Belén ; Perola, Markus ; Psaty, Bruce M ; Salomaa, Veikko ; Savage, David B ; Semple, Robert K ; Skaric-Juric, Tatjana ; Sigurdsson, Gunnar ; Song, Kijoung S ; Spector, Timothy D ; Syvänen, Ann-Christine ; Talmud, Philippa J ; Thorleifsson, Gudmar ; Thorsteinsdottir, Unnur ; Uitterlinden, André G ; van Duijn, Cornelia M ; Vidal-Puig, Antonio ; Wild, Sarah H ; Wright, Alan F ; Clegg, Deborah J ; Schadt, Eric ; Wilson, James ; Rudan, Igor ; Ripatti, Samuli ; Borecki, Ingrid B ; Shuldiner, Alan R ; Ingelsson, Erik ; Jansson, John-Olov ; Kaplan, Robert C ; Gudnason, Vilmundur ; Harris, Tamara B ; Groop, Leif ; Kiel, Douglas P ; Rivadeneira, Fernando ; Walker, Mark ; Barroso, Inês ; Vollenweider, Peter ; Waeber, Gérard ; Chambers, John C ; Kooner, Jaspal S ; Soranzo, Nicole ; Hirschhorn, Joel N ; Stefansson, Kari ; Wichmann, H-Erich ; Ohlsson, Claes ; O'Rahilly, Stephen ; Wareham, Nicholas J ; Speliotes, Elizabeth K ; Fox, Caroline S ; Laakso, Markku ; Loos, Ruth J F. / Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. In: Nature Genetics. 2011 ; Vol. 43, No. 8. pp. 753-60.
Bibtex
@article{d45a61715e674f7e87d5ca303efd1176,
title = "Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile",
abstract = "Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P <10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.",
keywords = "Adiponectin, Adiposity, Alleles, Body Fat Distribution, Body Mass Index, Body Weight, Female, Genetic Variation, Genome-Wide Association Study, Humans, Insulin Receptor Substrate Proteins, Intracellular Signaling Peptides and Proteins, Male, Meta-Analysis as Topic, Metabolome, Obesity, Polymorphism, Single Nucleotide, Subcutaneous Fat",
author = "{Oskari Kilpel{\"a}inen}, Tuomas and Zillikens, {M Carola} and Alena Stan{\v c}{\'a}kova and Finucane, {Francis M} and Ried, {Janina S} and Claudia Langenberg and Weihua Zhang and Beckmann, {Jacques S} and Jian'an Luan and Liesbeth Vandenput and Unnur Styrkarsdottir and Yanhua Zhou and Smith, {Albert Vernon} and Jing-Hua Zhao and Najaf Amin and Sailaja Vedantam and So-Youn Shin and Talin Haritunians and Mao Fu and Feitosa, {Mary F} and Meena Kumari and Halldorsson, {Bjarni V} and Emmi Tikkanen and Massimo Mangino and Caroline Hayward and Ci Song and Arnold, {Alice M} and Aulchenko, {Yurii S} and Oostra, {Ben A} and Harry Campbell and Cupples, {L Adrienne} and Davis, {Kathryn E} and Angela D{\"o}ring and Gudny Eiriksdottir and Karol Estrada and Fern{\'a}ndez-Real, {Jos{\'e} Manuel} and Melissa Garcia and Christian Gieger and Glazer, {Nicole L} and Candace Guiducci and Albert Hofman and Humphries, {Steve E} and Bo Isomaa and Jacobs, {Leonie C} and Antti Jula and David Karasik and Karlsson, {Magnus K} and Kay-Tee Khaw and Kim, {Lauren J} and Mika Kivim{\"a}ki and Norman Klopp and Brigitte K{\"u}hnel and Johanna Kuusisto and Yongmei Liu and Osten Ljunggren and Mattias Lorentzon and Luben, {Robert N} and Barbara McKnight and Dan Mellstr{\"o}m and Mitchell, {Braxton D} and Vincent Mooser and Moreno, {Jos{\'e} Maria} and Satu M{\"a}nnist{\"o} and O'Connell, {Jeffery R} and Laura Pascoe and Leena Peltonen and Bel{\'e}n Peral and Markus Perola and Psaty, {Bruce M} and Veikko Salomaa and Savage, {David B} and Semple, {Robert K} and Tatjana Skaric-Juric and Gunnar Sigurdsson and Song, {Kijoung S} and Spector, {Timothy D} and Ann-Christine Syv{\"a}nen and Talmud, {Philippa J} and Gudmar Thorleifsson and Unnur Thorsteinsdottir and Uitterlinden, {Andr{\'e} G} and {van Duijn}, {Cornelia M} and Antonio Vidal-Puig and Wild, {Sarah H} and Wright, {Alan F} and Clegg, {Deborah J} and Eric Schadt and James Wilson and Igor Rudan and Samuli Ripatti and Borecki, {Ingrid B} and Shuldiner, {Alan R} and Erik Ingelsson and John-Olov Jansson and Kaplan, {Robert C} and Vilmundur Gudnason and Harris, {Tamara B} and Leif Groop and Kiel, {Douglas P} and Fernando Rivadeneira and Mark Walker and In{\^e}s Barroso and Peter Vollenweider and G{\'e}rard Waeber and Chambers, {John C} and Kooner, {Jaspal S} and Nicole Soranzo and Hirschhorn, {Joel N} and Kari Stefansson and H-Erich Wichmann and Claes Ohlsson and Stephen O'Rahilly and Wareham, {Nicholas J} and Speliotes, {Elizabeth K} and Fox, {Caroline S} and Markku Laakso and Loos, {Ruth J F}",
year = "2011",
month = aug,
doi = "10.1038/ng.866",
language = "English",
volume = "43",
pages = "753--60",
journal = "Nature Genetics",
issn = "1061-4036",
publisher = "nature publishing group",
number = "8",
}
RIS
TY - JOUR
T1 - Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile
AU - Oskari Kilpeläinen, Tuomas
AU - Zillikens, M Carola
AU - Stančákova, Alena
AU - Finucane, Francis M
AU - Ried, Janina S
AU - Langenberg, Claudia
AU - Zhang, Weihua
AU - Beckmann, Jacques S
AU - Luan, Jian'an
AU - Vandenput, Liesbeth
AU - Styrkarsdottir, Unnur
AU - Zhou, Yanhua
AU - Smith, Albert Vernon
AU - Zhao, Jing-Hua
AU - Amin, Najaf
AU - Vedantam, Sailaja
AU - Shin, So-Youn
AU - Haritunians, Talin
AU - Fu, Mao
AU - Feitosa, Mary F
AU - Kumari, Meena
AU - Halldorsson, Bjarni V
AU - Tikkanen, Emmi
AU - Mangino, Massimo
AU - Hayward, Caroline
AU - Song, Ci
AU - Arnold, Alice M
AU - Aulchenko, Yurii S
AU - Oostra, Ben A
AU - Campbell, Harry
AU - Cupples, L Adrienne
AU - Davis, Kathryn E
AU - Döring, Angela
AU - Eiriksdottir, Gudny
AU - Estrada, Karol
AU - Fernández-Real, José Manuel
AU - Garcia, Melissa
AU - Gieger, Christian
AU - Glazer, Nicole L
AU - Guiducci, Candace
AU - Hofman, Albert
AU - Humphries, Steve E
AU - Isomaa, Bo
AU - Jacobs, Leonie C
AU - Jula, Antti
AU - Karasik, David
AU - Karlsson, Magnus K
AU - Khaw, Kay-Tee
AU - Kim, Lauren J
AU - Kivimäki, Mika
AU - Klopp, Norman
AU - Kühnel, Brigitte
AU - Kuusisto, Johanna
AU - Liu, Yongmei
AU - Ljunggren, Osten
AU - Lorentzon, Mattias
AU - Luben, Robert N
AU - McKnight, Barbara
AU - Mellström, Dan
AU - Mitchell, Braxton D
AU - Mooser, Vincent
AU - Moreno, José Maria
AU - Männistö, Satu
AU - O'Connell, Jeffery R
AU - Pascoe, Laura
AU - Peltonen, Leena
AU - Peral, Belén
AU - Perola, Markus
AU - Psaty, Bruce M
AU - Salomaa, Veikko
AU - Savage, David B
AU - Semple, Robert K
AU - Skaric-Juric, Tatjana
AU - Sigurdsson, Gunnar
AU - Song, Kijoung S
AU - Spector, Timothy D
AU - Syvänen, Ann-Christine
AU - Talmud, Philippa J
AU - Thorleifsson, Gudmar
AU - Thorsteinsdottir, Unnur
AU - Uitterlinden, André G
AU - van Duijn, Cornelia M
AU - Vidal-Puig, Antonio
AU - Wild, Sarah H
AU - Wright, Alan F
AU - Clegg, Deborah J
AU - Schadt, Eric
AU - Wilson, James
AU - Rudan, Igor
AU - Ripatti, Samuli
AU - Borecki, Ingrid B
AU - Shuldiner, Alan R
AU - Ingelsson, Erik
AU - Jansson, John-Olov
AU - Kaplan, Robert C
AU - Gudnason, Vilmundur
AU - Harris, Tamara B
AU - Groop, Leif
AU - Kiel, Douglas P
AU - Rivadeneira, Fernando
AU - Walker, Mark
AU - Barroso, Inês
AU - Vollenweider, Peter
AU - Waeber, Gérard
AU - Chambers, John C
AU - Kooner, Jaspal S
AU - Soranzo, Nicole
AU - Hirschhorn, Joel N
AU - Stefansson, Kari
AU - Wichmann, H-Erich
AU - Ohlsson, Claes
AU - O'Rahilly, Stephen
AU - Wareham, Nicholas J
AU - Speliotes, Elizabeth K
AU - Fox, Caroline S
AU - Laakso, Markku
AU - Loos, Ruth J F
PY - 2011/8
Y1 - 2011/8
N2 - Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P <10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
AB - Genome-wide association studies have identified 32 loci influencing body mass index, but this measure does not distinguish lean from fat mass. To identify adiposity loci, we meta-analyzed associations between ∼2.5 million SNPs and body fat percentage from 36,626 individuals and followed up the 14 most significant (P <10(-6)) independent loci in 39,576 individuals. We confirmed a previously established adiposity locus in FTO (P = 3 × 10(-26)) and identified two new loci associated with body fat percentage, one near IRS1 (P = 4 × 10(-11)) and one near SPRY2 (P = 3 × 10(-8)). Both loci contain genes with potential links to adipocyte physiology. Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels. Our findings provide new insights into adiposity and insulin resistance.
KW - Adiponectin
KW - Adiposity
KW - Alleles
KW - Body Fat Distribution
KW - Body Mass Index
KW - Body Weight
KW - Female
KW - Genetic Variation
KW - Genome-Wide Association Study
KW - Humans
KW - Insulin Receptor Substrate Proteins
KW - Intracellular Signaling Peptides and Proteins
KW - Male
KW - Meta-Analysis as Topic
KW - Metabolome
KW - Obesity
KW - Polymorphism, Single Nucleotide
KW - Subcutaneous Fat
U2 - 10.1038/ng.866
DO - 10.1038/ng.866
M3 - Journal article
C2 - 21706003
VL - 43
SP - 753
EP - 760
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 8
ER -
