CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Aurélien Macé; Marcus A Tuke; Patrick Deelen; Kati Kristiansson; Hannele Mattsson; Margit Nõukas; Yadav Sapkota; Ursula Schick; Eleonora Porcu; Sina Rüeger; Aaron F McDaid; David Porteous; Thomas W Winkler; Erika Salvi; Nick Shrine; Xueping Liu; Wei Q Ang; Weihua Zhang; Mary F Feitosa; Cristina Venturini; Peter J van der Most; Anders Rosengren; Andrew R Wood; Robin N Beaumont; Samuel E Jones; Katherine S Ruth; Hanieh Yaghootkar; Jessica Tyrrell; Aki S Havulinna; Harmen Boers; Reedik Mägi; Jennifer Kriebel; Martina Müller-Nurasyid; Markus Perola; Markku Nieminen; Marja-Liisa Lokki; Mika Kähönen; Jorma S Viikari; Frank Geller; Jari Lahti; Aarno Palotie; Päivikki Koponen; Annamari Lundqvist; Harri Rissanen; Erwin P Bottinger; Saima Afaq; Mary K Wojczynski; Petra Lenzini; Ilja M Nolte; Thomas Sparsø; Nicole Schupf; Kaare Christensen; Thomas T Perls; Anne B Newman; Thomas Werge; Harold Snieder; Timothy D Spector; John C Chambers; Seppo Koskinen; Mads Melbye; Olli T Raitakari; Terho Lehtimäki; Martin D Tobin; Louise V Wain; Juha Sinisalo; Annette Peters; Thomas Meitinger; Nicholas G Martin; Naomi R Wray; Grant W Montgomery; Sarah E Medland; Morris A Swertz; Erkki Vartiainen; Katja Borodulin; Satu Männistö; Anna Murray; Murielle Bochud; Sébastien Jacquemont; Fernando Rivadeneira; Thomas F Hansen; Albertine J Oldehinkel; Massimo Mangino; Michael A Province; Panos Deloukas; Jaspal S Kooner; Rachel M Freathy; Craig Pennell; Bjarke Feenstra; David P Strachan; Guillaume Lettre; Joel Hirschhorn; Daniele Cusi; Iris M Heid; Caroline Hayward; Katrin Männik; Jacques S Beckmann; Ruth J F Loos; Dale R Nyholt; Andres Metspalu; Johan G Eriksson; Michael N Weedon; Veikko Salomaa; Lude Franke; Alexandre Reymond; Timothy M Frayling; Zoltán Kutalik

doi:10.1038/s41467-017-00556-x

CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Aurélien Macé, Marcus A Tuke, Patrick Deelen, Kati Kristiansson, Hannele Mattsson, Margit Nõukas, Yadav Sapkota, Ursula Schick, Eleonora Porcu, Sina Rüeger, Aaron F McDaid, David Porteous, Thomas W Winkler, Erika Salvi, Nick Shrine, Xueping Liu, Wei Q Ang, Weihua Zhang, Mary F Feitosa, Cristina VenturiniPeter J van der Most, Anders Rosengren, Andrew R Wood, Robin N Beaumont, Samuel E Jones, Katherine S Ruth, Hanieh Yaghootkar, Jessica Tyrrell, Aki S Havulinna, Harmen Boers, Reedik Mägi, Jennifer Kriebel, Martina Müller-Nurasyid, Markus Perola, Markku Nieminen, Marja-Liisa Lokki, Mika Kähönen, Jorma S Viikari, Frank Geller, Jari Lahti, Aarno Palotie, Päivikki Koponen, Annamari Lundqvist, Harri Rissanen, Erwin P Bottinger, Saima Afaq, Mary K Wojczynski, Petra Lenzini, Ilja M Nolte, Thomas Sparsø, Nicole Schupf, Kaare Christensen, Thomas T Perls, Anne B Newman, Thomas Werge, Harold Snieder, Timothy D Spector, John C Chambers, Seppo Koskinen, Mads Melbye, Olli T Raitakari, Terho Lehtimäki, Martin D Tobin, Louise V Wain, Juha Sinisalo, Annette Peters, Thomas Meitinger, Nicholas G Martin, Naomi R Wray, Grant W Montgomery, Sarah E Medland, Morris A Swertz, Erkki Vartiainen, Katja Borodulin, Satu Männistö, Anna Murray, Murielle Bochud, Sébastien Jacquemont, Fernando Rivadeneira, Thomas F Hansen, Albertine J Oldehinkel, Massimo Mangino, Michael A Province, Panos Deloukas, Jaspal S Kooner, Rachel M Freathy, Craig Pennell, Bjarke Feenstra, David P Strachan, Guillaume Lettre, Joel Hirschhorn, Daniele Cusi, Iris M Heid, Caroline Hayward, Katrin Männik, Jacques S Beckmann, Ruth J F Loos, Dale R Nyholt, Andres Metspalu, Johan G Eriksson, Michael N Weedon, Veikko Salomaa, Lude Franke, Alexandre Reymond, Timothy M Frayling, Zoltán Kutalik

Institut for Klinisk Medicin

28 Citationer (Scopus)

24 Downloads (Pure)

Abstract

There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m²). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m² for each Mb of total deletion burden (P = 2.5 × 10^-10, 6.0 × 10^-5, and 2.9 × 10^-3). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.

Originalsprog	Engelsk
Artikelnummer	744
Tidsskrift	Nature Communications
Vol/bind	8
Antal sider	11
ISSN	2041-1723
DOI	https://doi.org/10.1038/s41467-017-00556-x
Status	Udgivet - 1 dec. 2017

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10.1038/s41467-017-00556-xLicens: CC BY

CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traitsForlagets udgivne version, 1,16 MBLicens: CC BY

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Macé, A., Tuke, M. A., Deelen, P., Kristiansson, K., Mattsson, H., Nõukas, M., Sapkota, Y., Schick, U., Porcu, E., Rüeger, S., McDaid, A. F., Porteous, D., Winkler, T. W., Salvi, E., Shrine, N., Liu, X., Ang, W. Q., Zhang, W., Feitosa, M. F., ... Kutalik, Z. (2017). CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits. Nature Communications, 8, [744]. https://doi.org/10.1038/s41467-017-00556-x

Macé, A, Tuke, MA, Deelen, P, Kristiansson, K, Mattsson, H, Nõukas, M, Sapkota, Y, Schick, U, Porcu, E, Rüeger, S, McDaid, AF, Porteous, D, Winkler, TW, Salvi, E, Shrine, N, Liu, X, Ang, WQ, Zhang, W, Feitosa, MF, Venturini, C, van der Most, PJ, Rosengren, A, Wood, AR, Beaumont, RN, Jones, SE, Ruth, KS, Yaghootkar, H, Tyrrell, J, Havulinna, AS, Boers, H, Mägi, R, Kriebel, J, Müller-Nurasyid, M, Perola, M, Nieminen, M, Lokki, M-L, Kähönen, M, Viikari, JS, Geller, F, Lahti, J, Palotie, A, Koponen, P, Lundqvist, A, Rissanen, H, Bottinger, EP, Afaq, S, Wojczynski, MK, Lenzini, P, Nolte, IM, Sparsø, T, Schupf, N, Christensen, K, Perls, TT, Newman, AB, Werge, T, Snieder, H, Spector, TD, Chambers, JC, Koskinen, S, Melbye, M, Raitakari, OT, Lehtimäki, T, Tobin, MD, Wain, LV, Sinisalo, J, Peters, A, Meitinger, T, Martin, NG, Wray, NR, Montgomery, GW, Medland, SE, Swertz, MA, Vartiainen, E, Borodulin, K, Männistö, S, Murray, A, Bochud, M, Jacquemont, S, Rivadeneira, F, Hansen, TF, Oldehinkel, AJ, Mangino, M, Province, MA, Deloukas, P, Kooner, JS, Freathy, RM, Pennell, C, Feenstra, B, Strachan, DP, Lettre, G, Hirschhorn, J, Cusi, D, Heid, IM, Hayward, C, Männik, K, Beckmann, JS, Loos, RJF, Nyholt, DR, Metspalu, A, Eriksson, JG, Weedon, MN, Salomaa, V, Franke, L, Reymond, A, Frayling, TM & Kutalik, Z 2017, 'CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits', Nature Communications, bind 8, 744. https://doi.org/10.1038/s41467-017-00556-x

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abstract = "There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 × 10-10, 6.0 × 10-5, and 2.9 × 10-3). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.",

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TY - JOUR

T1 - CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

AU - Macé, Aurélien

AU - Tuke, Marcus A

AU - Deelen, Patrick

AU - Kristiansson, Kati

AU - Mattsson, Hannele

AU - Nõukas, Margit

AU - Sapkota, Yadav

AU - Schick, Ursula

AU - Porcu, Eleonora

AU - Rüeger, Sina

AU - McDaid, Aaron F

AU - Porteous, David

AU - Winkler, Thomas W

AU - Salvi, Erika

AU - Shrine, Nick

AU - Liu, Xueping

AU - Ang, Wei Q

AU - Zhang, Weihua

AU - Feitosa, Mary F

AU - Venturini, Cristina

AU - van der Most, Peter J

AU - Rosengren, Anders

AU - Wood, Andrew R

AU - Beaumont, Robin N

AU - Jones, Samuel E

AU - Ruth, Katherine S

AU - Yaghootkar, Hanieh

AU - Tyrrell, Jessica

AU - Havulinna, Aki S

AU - Boers, Harmen

AU - Mägi, Reedik

AU - Kriebel, Jennifer

AU - Müller-Nurasyid, Martina

AU - Perola, Markus

AU - Nieminen, Markku

AU - Lokki, Marja-Liisa

AU - Kähönen, Mika

AU - Viikari, Jorma S

AU - Geller, Frank

AU - Lahti, Jari

AU - Palotie, Aarno

AU - Koponen, Päivikki

AU - Lundqvist, Annamari

AU - Rissanen, Harri

AU - Bottinger, Erwin P

AU - Afaq, Saima

AU - Wojczynski, Mary K

AU - Lenzini, Petra

AU - Nolte, Ilja M

AU - Sparsø, Thomas

AU - Schupf, Nicole

AU - Christensen, Kaare

AU - Perls, Thomas T

AU - Newman, Anne B

AU - Werge, Thomas

AU - Snieder, Harold

AU - Spector, Timothy D

AU - Chambers, John C

AU - Koskinen, Seppo

AU - Melbye, Mads

AU - Raitakari, Olli T

AU - Lehtimäki, Terho

AU - Tobin, Martin D

AU - Wain, Louise V

AU - Sinisalo, Juha

AU - Peters, Annette

AU - Meitinger, Thomas

AU - Martin, Nicholas G

AU - Wray, Naomi R

AU - Montgomery, Grant W

AU - Medland, Sarah E

AU - Swertz, Morris A

AU - Vartiainen, Erkki

AU - Borodulin, Katja

AU - Männistö, Satu

AU - Murray, Anna

AU - Bochud, Murielle

AU - Jacquemont, Sébastien

AU - Rivadeneira, Fernando

AU - Hansen, Thomas F

AU - Oldehinkel, Albertine J

AU - Mangino, Massimo

AU - Province, Michael A

AU - Deloukas, Panos

AU - Kooner, Jaspal S

AU - Freathy, Rachel M

AU - Pennell, Craig

AU - Feenstra, Bjarke

AU - Strachan, David P

AU - Lettre, Guillaume

AU - Hirschhorn, Joel

AU - Cusi, Daniele

AU - Heid, Iris M

AU - Hayward, Caroline

AU - Männik, Katrin

AU - Beckmann, Jacques S

AU - Loos, Ruth J F

AU - Nyholt, Dale R

AU - Metspalu, Andres

AU - Eriksson, Johan G

AU - Weedon, Michael N

AU - Salomaa, Veikko

AU - Franke, Lude

AU - Reymond, Alexandre

AU - Frayling, Timothy M

AU - Kutalik, Zoltán

PY - 2017/12/1

Y1 - 2017/12/1

N2 - There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 × 10-10, 6.0 × 10-5, and 2.9 × 10-3). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.

AB - There are few examples of robust associations between rare copy number variants (CNVs) and complex continuous human traits. Here we present a large-scale CNV association meta-analysis on anthropometric traits in up to 191,161 adult samples from 26 cohorts. The study reveals five CNV associations at 1q21.1, 3q29, 7q11.23, 11p14.2, and 18q21.32 and confirms two known loci at 16p11.2 and 22q11.21, implicating at least one anthropometric trait. The discovered CNVs are recurrent and rare (0.01-0.2%), with large effects on height (>2.4 cm), weight (>5 kg), and body mass index (BMI) (>3.5 kg/m2). Burden analysis shows a 0.41 cm decrease in height, a 0.003 increase in waist-to-hip ratio and increase in BMI by 0.14 kg/m2 for each Mb of total deletion burden (P = 2.5 × 10-10, 6.0 × 10-5, and 2.9 × 10-3). Our study provides evidence that the same genes (e.g., MC4R, FIBIN, and FMO5) harbor both common and rare variants affecting body size and that anthropometric traits share genetic loci with developmental and psychiatric disorders.

KW - Journal Article

U2 - 10.1038/s41467-017-00556-x

DO - 10.1038/s41467-017-00556-x

M3 - Journal article

C2 - 28963451

SN - 2041-1723

VL - 8

JO - Nature Communications

JF - Nature Communications

M1 - 744

ER -

CNV-association meta-analysis in 191,161 European adults reveals new loci associated with anthropometric traits

Abstract

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