Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.

Heid, I.M.; Jackson, A.U.; Randall, J.C.; Winkler, T.W.; Qi, L.; Steinthorsdottir, V.; Thorleifsson, G.; Zillikens, M.C.; Speliotes, E.K.; Mägi, R.; Workalemahu, T.; White, C.C.; Bouatia-Naji, N.; Harris, T.B.; Berndt, S.I.; Ingelsson, E.; Willer, C.J.; Weedon, M.N.; Luan, J.; Vedantam, S.; Esko, T.; Kilpeläinen, T.O.; Kutalik, Z.; Li, S.; Monda, K.L.; Dixon, A.L.; Holmes, C.C.; Kaplan, L.M.; Liang, L.; Min, J.L.; Moffatt, M.F.; Molony, C.; Nicholson, G.; Schadt, E.E.; Zondervan, K.T.; Feitosa, M.F.; Ferreira, T.; Allen, H.L.; Weyant, R.J.; Wheeler, E.; Wood, A.R.; MAGIC,; Estrada, K.; Estrada, K.; Goddard, M.E.; Lettre, G.; Mangino, M.; Nyholt, D.R.; Purcell, S.; Smith, A.V.; Visscher, P.M.; Yang, J.; McCarroll, S.A.; Nemesh, J.; Voight, B.F.; Absher, D.; Amin, N.; Aspelund, T.; Coin, L.; Glazer, N.L.; Hayward, C.; Heard-Costa, N.L.; Hottenga, J.J.; Johansson, A.; Johnson, T.; Kaakinen, M.; Kapur, K.; Ketkar, S.; Knowles, J.W.; Kraft, P.; Kraja, A.T.; Lamina, C.; Leitzmann, M.F.; McKnight, B.; Morris, A.P.; Ong, K.K.; Perry, J.R.; Peters, M.J.; Polasek, O.; Prokopenko, I.; Rayner, N.W.; Ripatti, S.; Rivadeneira, F.; Robertson, N.R.; Sanna, S.; Sovio, U.; Surakka, I.; Teumer, A.; van Wingerden, S.; Vitart, V.; Zhao, J.H.; Cavalcanti-Proença, C.; Chines, P.S.; Fisher, E.; Kulzer, J.R.; Lecoeur, C.; Narisu, N.; Sandholt, C.; Scott, L.J.; Silander, K.; Stark, K.; Tammesoo, M.L.; Teslovich, T.M.; Timpson, N.J.; Watanabe, R.M.; Welch, R.; Chasman, D.I.; Cooper, M.N.; Jansson, J.O.; Kettunen, J.; Lawrence, R.W.; Pellikka, N.; Perola, M.; Vandenput, L.; Alavere, H.; Almgren, P.; Atwood, L.D.; Bennett, A.J.; Biffar, R.; Bonnycastle, L.L.; Bornstein, S.R.; Buchanan, T.A.; Campbell, H.; Day, I.N.; Dei, M.; Dörr, M.; Elliott, P.; Erdos, M.R.; Eriksson, J.G.; Freimer, N.B.; Fu, M.; Gaget, S.; Geus, E.J.; Gjesing, A.P.; Grallert, H.; Grässler, J.; Groves, C.J.; Guiducci, C.; Hartikainen, A.L.; Hassanali, N.; Havulinna, A.S.; Herzig, K.H.; Hicks, A.A.; Hui, J.; Igl, W.; Jousilahti, P.; Jula, A.; Kajantie, E.; Kinnunen, L.; Kolcic, I.; Koskinen, S.; Kovacs, P.; Kroemer, H.K.; Krzelj, V.; Kuusisto, J.; Kvaloy, K.; Laitinen, J.; Lantieri, O.; Lathrop, G.M.; Lokki, M.L.; Luben, R.N.; Ludwig, B.; McArdle, W.L.; McCarthy, A.; Morken, M.A.; Nelis, M.; Neville, M.J.; Paré, G.; Parker, A.N.; Peden, J.F.; Pichler, I.; Pietiläinen, K.H.; Platou, C.G.; Pouta, A.; Ridderstråle, M.; Samani, N.J.; Saramies, J.; Sinisalo, J.; Smit, J.H.; Strawbridge, R.J.; Stringham, H.M.; Swift, A.J.; Teder-Laving, M.; Thomson, B.; Usala, G.; van Meurs, J.B.; van Ommen, G.J.; Vatin, V.; Volpato, C.B.; Wallaschofski, H.; Walters, G.B.; Widen, E.; Wild, S.H.; Willemsen, G.; Witte, D.R.; Zgaga, L.; Zitting, P.; Beilby, J.P.; James, A.L.; Kähönen, M.; Lehtimäki, T.; Nieminen, M.S.; Ohlsson, C.; Palmer, L.J.; Raitakari, O.; Ridker, P.M.; Stumvoll, M.; Tönjes, A.; Viikari, J.; Balkau, B.; Ben-Shlomo, Y.; Bergman, R.N.; Boeing, H.; Smith, G.D.; Ebrahim, S.; Froguel, P.; Hansen, T.; Hengstenberg, C.; Hveem, K.; Isomaa, B.; Jørgensen, T.; Karpe, F.; Khaw, K.T.; Laakso, M.; Lawlor, D.A.; Marre, M.; Meitinger, T.; Metspalu, A.; Midthjell, K.; Pedersen, O.; Salomaa, V.; Schwarz, P.E.; Tuomi, T.; Tuomilehto, J.; Valle, T.T.; Wareham, N.J.; Arnold, A.M.; Beckmann, J.S.; Bergmann, S.; Boerwinkle, E.; Boomsma, D.I.; Caulfield, M.J.; Collins, F.S.; Eiriksdottir, G.; Gudnason, V.; Gyllensten, U.; Hamsten, A.; Hattersley, A.T.; Hofman, A.; Hu, F.B.; Illig, T.; Iribarren, C.; Jarvelin, M.R.; Kao, W.H.; Kaprio, J.; Launer, L.J.; Munroe, P.B.; Oostra, B.; Penninx, B.W.; Pramstaller, P.P.; Psaty, B.M.; Quertermous, T.; Rissanen, A.; Rudan, I.; Shuldiner, A.R.; Soranzo, N.; Spector, T.D.; Syvanen, A.C.; Uda, M.; Uitterlinden, A.; Völzke, H.; Vollenweider, P.; Wilson, J.F.; Witteman, J.C.; Wright, A.F.; Abecasis, G.R.; Boehnke, M.; Borecki, I.B.; Deloukas, P.; Frayling, T.M.; Groop, L.C.; Haritunians, T.; Hunter, D.J.; Kaplan, R.C.; North, K.E.; O'Connell, J.R.; Peltonen, L.; Schlessinger, D.; Strachan, D.P.; Hirschhorn, J.N.; Assimes, T.L.; Wichmann, H.E.; Thorsteinsdottir, U.; van Duijn, C.M.; Stefansson, K.; Cupples, L.A.; Loos, R.J.; Barroso, I.; McCarthy, M.I.; Fox, C.S.; Mohlke, K.L.; Lindgren, C.M.

doi:10.1038/ng.685

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.

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Serval ID

serval:BIB_0DA88425D5DD

Type

Article: article from journal or magazin.

Collection

Publications

Institution

UNIL/CHUV

Title

Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution.

Journal

Nature Genetics

Author(s)

Heid I.M., Jackson A.U., Randall J.C., Winkler T.W., Qi L., Steinthorsdottir V., Thorleifsson G., Zillikens M.C., Speliotes E.K., Mägi R., Workalemahu T., White C.C., Bouatia-Naji N., Harris T.B., Berndt S.I., Ingelsson E., Willer C.J., Weedon M.N., Luan J., Vedantam S., Esko T., Kilpeläinen T.O., Kutalik Z., Li S., Monda K.L., Dixon A.L., Holmes C.C., Kaplan L.M., Liang L., Min J.L., Moffatt M.F., Molony C., Nicholson G., Schadt E.E., Zondervan K.T., Feitosa M.F., Ferreira T., Allen H.L., Weyant R.J., Wheeler E., Wood A.R., MAGIC , Estrada K., Estrada K., Goddard M.E., Lettre G., Mangino M., Nyholt D.R., Purcell S., Smith A.V., Visscher P.M., Yang J., McCarroll S.A., Nemesh J., Voight B.F., Absher D., Amin N., Aspelund T., Coin L., Glazer N.L., Hayward C., Heard-Costa N.L., Hottenga J.J., Johansson A., Johnson T., Kaakinen M., Kapur K., Ketkar S., Knowles J.W., Kraft P., Kraja A.T., Lamina C., Leitzmann M.F., McKnight B., Morris A.P., Ong K.K., Perry J.R., Peters M.J., Polasek O., Prokopenko I., Rayner N.W., Ripatti S., Rivadeneira F., Robertson N.R., Sanna S., Sovio U., Surakka I., Teumer A., van Wingerden S., Vitart V., Zhao J.H., Cavalcanti-Proença C., Chines P.S., Fisher E., Kulzer J.R., Lecoeur C., Narisu N., Sandholt C., Scott L.J., Silander K., Stark K., Tammesoo M.L., Teslovich T.M., Timpson N.J., Watanabe R.M., Welch R., Chasman D.I., Cooper M.N., Jansson J.O., Kettunen J., Lawrence R.W., Pellikka N., Perola M., Vandenput L., Alavere H., Almgren P., Atwood L.D., Bennett A.J., Biffar R., Bonnycastle L.L., Bornstein S.R., Buchanan T.A., Campbell H., Day I.N., Dei M., Dörr M., Elliott P., Erdos M.R., Eriksson J.G., Freimer N.B., Fu M., Gaget S., Geus E.J., Gjesing A.P., Grallert H., Grässler J., Groves C.J., Guiducci C., Hartikainen A.L., Hassanali N., Havulinna A.S., Herzig K.H., Hicks A.A., Hui J., Igl W., Jousilahti P., Jula A., Kajantie E., Kinnunen L., Kolcic I., Koskinen S., Kovacs P., Kroemer H.K., Krzelj V., Kuusisto J., Kvaloy K., Laitinen J., Lantieri O., Lathrop G.M., Lokki M.L., Luben R.N., Ludwig B., McArdle W.L., McCarthy A., Morken M.A., Nelis M., Neville M.J., Paré G., Parker A.N., Peden J.F., Pichler I., Pietiläinen K.H., Platou C.G., Pouta A., Ridderstråle M., Samani N.J., Saramies J., Sinisalo J., Smit J.H., Strawbridge R.J., Stringham H.M., Swift A.J., Teder-Laving M., Thomson B., Usala G., van Meurs J.B., van Ommen G.J., Vatin V., Volpato C.B., Wallaschofski H., Walters G.B., Widen E., Wild S.H., Willemsen G., Witte D.R., Zgaga L., Zitting P., Beilby J.P., James A.L., Kähönen M., Lehtimäki T., Nieminen M.S., Ohlsson C., Palmer L.J., Raitakari O., Ridker P.M., Stumvoll M., Tönjes A., Viikari J., Balkau B., Ben-Shlomo Y., Bergman R.N., Boeing H., Smith G.D., Ebrahim S., Froguel P., Hansen T., Hengstenberg C., Hveem K., Isomaa B., Jørgensen T., Karpe F., Khaw K.T., Laakso M., Lawlor D.A., Marre M., Meitinger T., Metspalu A., Midthjell K., Pedersen O., Salomaa V., Schwarz P.E., Tuomi T., Tuomilehto J., Valle T.T., Wareham N.J., Arnold A.M., Beckmann J.S., Bergmann S., Boerwinkle E., Boomsma D.I., Caulfield M.J., Collins F.S., Eiriksdottir G., Gudnason V., Gyllensten U., Hamsten A., Hattersley A.T., Hofman A., Hu F.B., Illig T., Iribarren C., Jarvelin M.R., Kao W.H., Kaprio J., Launer L.J., Munroe P.B., Oostra B., Penninx B.W., Pramstaller P.P., Psaty B.M., Quertermous T., Rissanen A., Rudan I., Shuldiner A.R., Soranzo N., Spector T.D., Syvanen A.C., Uda M., Uitterlinden A., Völzke H., Vollenweider P., Wilson J.F., Witteman J.C., Wright A.F., Abecasis G.R., Boehnke M., Borecki I.B., Deloukas P., Frayling T.M., Groop L.C., Haritunians T., Hunter D.J., Kaplan R.C., North K.E., O'Connell J.R., Peltonen L., Schlessinger D., Strachan D.P., Hirschhorn J.N., Assimes T.L., Wichmann H.E., Thorsteinsdottir U., van Duijn C.M., Stefansson K., Cupples L.A., Loos R.J., Barroso I., McCarthy M.I., Fox C.S., Mohlke K.L., Lindgren C.M.

ISSN

1546-1718[electronic], 1061-4036[linking]

Publication state

Published

Issued date

2010

Peer-reviewed

Oui

Volume

Number

Pages

949-960

Language

english

Notes

Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't Publication Status: ppublish

Abstract

Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects). We identified 13 new loci in or near RSPO3, VEGFA, TBX15-WARS2, NFE2L3, GRB14, DNM3-PIGC, ITPR2-SSPN, LY86, HOXC13, ADAMTS9, ZNRF3-KREMEN1, NISCH-STAB1 and CPEB4 (P = 1.9 × 10⁻⁹ to P = 1.8 × 10⁻⁴⁰) and the known signal at LYPLAL1. Seven of these loci exhibited marked sexual dimorphism, all with a stronger effect on WHR in women than men (P for sex difference = 1.9 × 10⁻³ to P = 1.2 × 10⁻³). These findings provide evidence for multiple loci that modulate body fat distribution independent of overall adiposity and reveal strong gene-by-sex interactions.

Keywords

Adipose Tissue/anatomy & histology, Age Factors, Chromosome Mapping, Female, Genome, Human, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Sex Characteristics, Waist-Hip Ratio , Colaus Study

URN

urn:nbn:ch:serval-BIB_0DA88425D5DD1

OAI-PMH

oai:serval.unil.ch:BIB_0DA88425D5DD

DOI

10.1038/ng.685

Pubmed

20935629

Web of science

000283540500011

Create date

24/11/2010 11:22