Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of european descent confirm known loci and reveal several novel associations

Sachiko Yoneyama; Yiran Guo; Matthew B. Lanktree; Michael R. Barnes; Clara C. Elbers; Konrad J. Karczewski; Sandosh Padmanabhan; Florianne Bauer; Jens Baumert; Amber Beitelshees; Gerald S. Berenson; Jolanda M.A. Boer; Gregory Burke; Brian Cade; Wei Chen; Rhonda M. Cooper-Dehoff; Tom R. Gaunt; Christian Gieger; Yan Gong; Mathias Gorski; Nancy Heard-Costa; Toby Johnson; Michael J. Lamonte; Caitrin Mcdonough; Keri L. Monda; N. Charlotte Onland-Moret; Christopher P. Nelson; Jeffrey R. O'Connell; Jose Ordovas; Inga Peter; Annette Peters; Jonathan Shaffer; Haiqinq Shen; Erin Smith; Liz Speilotes; Fridtjof Thomas; Barbara Thorand; W. M.Monique Verschuren; Sonia S. Anand; Anna Dominiczak; Karina W. Davidson; Robert A. Hegele; Iris Heid; Marten H. Hofker; Gordon S. Huggins; Thomas Illig; Julie A. Johnson; Susan Kirkland; Wolfgang König; Taimour Y. Langaee; Jeanne Mccaffery; Olle Melander; Braxton D. Mitchell; Patricia Munroe; Sarah S. Murray; George Papanicolaou; Susan Redline; Muredach Reilly; Nilesh J. Samani; Nicholas J. Schork; Yvonne T. Van Der Schouw; Daichi Shimbo; Alan R. Shuldiner; Martin D. Tobin; Cisca Wijmenga; Salim Yusuf; Hakon Hakonarson; Leslie A. Lange; Ellen W. Demerath; Caroline S. Fox; Kari E. North; Alex P. Reiner; Brendan Keating; Kira C. Taylor

doi:10.1093/hmg/ddt626

Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of european descent confirm known loci and reveal several novel associations

Sachiko Yoneyama, Yiran Guo, Matthew B. Lanktree, Michael R. Barnes, Clara C. Elbers, Konrad J. Karczewski, Sandosh Padmanabhan, Florianne Bauer, Jens Baumert, Amber Beitelshees, Gerald S. Berenson, Jolanda M.A. Boer, Gregory Burke, Brian Cade, Wei Chen, Rhonda M. Cooper-Dehoff, Tom R. Gaunt, Christian Gieger, Yan Gong, Mathias GorskiNancy Heard-Costa, Toby Johnson, Michael J. Lamonte, Caitrin Mcdonough, Keri L. Monda, N. Charlotte Onland-Moret, Christopher P. Nelson, Jeffrey R. O'Connell, Jose Ordovas, Inga Peter, Annette Peters, Jonathan Shaffer, Haiqinq Shen, Erin Smith, Liz Speilotes, Fridtjof Thomas, Barbara Thorand, W. M.Monique Verschuren, Sonia S. Anand, Anna Dominiczak, Karina W. Davidson, Robert A. Hegele, Iris Heid, Marten H. Hofker, Gordon S. Huggins, Thomas Illig, Julie A. Johnson, Susan Kirkland, Wolfgang König, Taimour Y. Langaee, Jeanne Mccaffery, Olle Melander, Braxton D. Mitchell, Patricia Munroe, Sarah S. Murray, George Papanicolaou, Susan Redline, Muredach Reilly, Nilesh J. Samani, Nicholas J. Schork, Yvonne T. Van Der Schouw, Daichi Shimbo, Alan R. Shuldiner, Martin D. Tobin, Cisca Wijmenga, Salim Yusuf, Hakon Hakonarson, Leslie A. Lange, Ellen W. Demerath, Caroline S. Fox, Kari E. North, Alex P. Reiner, Brendan Keating, Kira C. Taylor

Medicine

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

24 Citas (Scopus)

Resumen

Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ̃50 000 cosmopolitan tagged SNPs across̃2100cardiovascular-related genes. Eachtraitwasmodeled asa function of age, study siteandprincipal components to control for population stratification, andweconducted a fixed-effectsmeta-analysis. Nonewloci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 ×10^-6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β±SE, 0.048±0.008, P=7.7×10^-9) as was rs7302703-G in HOXC10 (β=0.044±0.008, P=2.9×10^-7) and rs936108-C in PEMT (β-0.035±0.007, P=1.9×10^-6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β=0.10±0.02, P=1.9×10^-6) and rs1037575-A in ATBDB4 (β=0.046±0.01, P=2.2×10^-6), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

Idioma original	English
Número de artículo	ddt626
Páginas (desde-hasta)	2498-2510
Número de páginas	13
Publicación	Human Molecular Genetics
Volumen	23
N.º	9
DOI	https://doi.org/10.1093/hmg/ddt626
Estado	Published - may. 2014

ASJC Scopus Subject Areas

Molecular Biology
Genetics
Genetics(clinical)

ODS de las Naciones Unidas

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10.1093/hmg/ddt626

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Yoneyama, S., Guo, Y., Lanktree, M. B., Barnes, M. R., Elbers, C. C., Karczewski, K. J., Padmanabhan, S., Bauer, F., Baumert, J., Beitelshees, A., Berenson, G. S., Boer, J. M. A., Burke, G., Cade, B., Chen, W., Cooper-Dehoff, R. M., Gaunt, T. R., Gieger, C., Gong, Y., ... Taylor, K. C. (2014). Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of european descent confirm known loci and reveal several novel associations. Human Molecular Genetics, 23(9), 2498-2510. Artículo ddt626. https://doi.org/10.1093/hmg/ddt626

Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of european descent confirm known loci and reveal several novel associations. / Yoneyama, Sachiko; Guo, Yiran; Lanktree, Matthew B. et al.
En: Human Molecular Genetics, Vol. 23, N.º 9, ddt626, 05.2014, p. 2498-2510.

Producción científica: Contribución a una revista › Artículo › revisión exhaustiva

Yoneyama, S, Guo, Y, Lanktree, MB, Barnes, MR, Elbers, CC, Karczewski, KJ, Padmanabhan, S, Bauer, F, Baumert, J, Beitelshees, A, Berenson, GS, Boer, JMA, Burke, G, Cade, B, Chen, W, Cooper-Dehoff, RM, Gaunt, TR, Gieger, C, Gong, Y, Gorski, M, Heard-Costa, N, Johnson, T, Lamonte, MJ, Mcdonough, C, Monda, KL, Onland-Moret, NC, Nelson, CP, O'Connell, JR, Ordovas, J, Peter, I, Peters, A, Shaffer, J, Shen, H, Smith, E, Speilotes, L, Thomas, F, Thorand, B, Verschuren, WMM, Anand, SS, Dominiczak, A, Davidson, KW, Hegele, RA, Heid, I, Hofker, MH, Huggins, GS, Illig, T, Johnson, JA, Kirkland, S, König, W, Langaee, TY, Mccaffery, J, Melander, O, Mitchell, BD, Munroe, P, Murray, SS, Papanicolaou, G, Redline, S, Reilly, M, Samani, NJ, Schork, NJ, Van Der Schouw, YT, Shimbo, D, Shuldiner, AR, Tobin, MD, Wijmenga, C, Yusuf, S, Hakonarson, H, Lange, LA, Demerath, EW, Fox, CS, North, KE, Reiner, AP, Keating, B & Taylor, KC 2014, 'Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of european descent confirm known loci and reveal several novel associations', Human Molecular Genetics, vol. 23, n.º 9, ddt626, pp. 2498-2510. https://doi.org/10.1093/hmg/ddt626

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title = "Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of european descent confirm known loci and reveal several novel associations",

abstract = "Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes{\~ }50 000 cosmopolitan tagged SNPs acros{\~s}2100cardiovascular-related genes. Eachtraitwasmodeled asa function of age, study siteandprincipal components to control for population stratification, andweconducted a fixed-effectsmeta-analysis. Nonewloci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 ×10-6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β±SE, 0.048±0.008, P=7.7×10-9) as was rs7302703-G in HOXC10 (β=0.044±0.008, P=2.9×10-7) and rs936108-C in PEMT (β-0.035±0.007, P=1.9×10-6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β=0.10±0.02, P=1.9×10-6) and rs1037575-A in ATBDB4 (β=0.046±0.01, P=2.2×10-6), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.",

author = "Sachiko Yoneyama and Yiran Guo and Lanktree, {Matthew B.} and Barnes, {Michael R.} and Elbers, {Clara C.} and Karczewski, {Konrad J.} and Sandosh Padmanabhan and Florianne Bauer and Jens Baumert and Amber Beitelshees and Berenson, {Gerald S.} and Boer, {Jolanda M.A.} and Gregory Burke and Brian Cade and Wei Chen and Cooper-Dehoff, {Rhonda M.} and Gaunt, {Tom R.} and Christian Gieger and Yan Gong and Mathias Gorski and Nancy Heard-Costa and Toby Johnson and Lamonte, {Michael J.} and Caitrin Mcdonough and Monda, {Keri L.} and Onland-Moret, {N. Charlotte} and Nelson, {Christopher P.} and O'Connell, {Jeffrey R.} and Jose Ordovas and Inga Peter and Annette Peters and Jonathan Shaffer and Haiqinq Shen and Erin Smith and Liz Speilotes and Fridtjof Thomas and Barbara Thorand and Verschuren, {W. M.Monique} and Anand, {Sonia S.} and Anna Dominiczak and Davidson, {Karina W.} and Hegele, {Robert A.} and Iris Heid and Hofker, {Marten H.} and Huggins, {Gordon S.} and Thomas Illig and Johnson, {Julie A.} and Susan Kirkland and Wolfgang K{\"o}nig and Langaee, {Taimour Y.} and Jeanne Mccaffery and Olle Melander and Mitchell, {Braxton D.} and Patricia Munroe and Murray, {Sarah S.} and George Papanicolaou and Susan Redline and Muredach Reilly and Samani, {Nilesh J.} and Schork, {Nicholas J.} and {Van Der Schouw}, {Yvonne T.} and Daichi Shimbo and Shuldiner, {Alan R.} and Tobin, {Martin D.} and Cisca Wijmenga and Salim Yusuf and Hakon Hakonarson and Lange, {Leslie A.} and Demerath, {Ellen W.} and Fox, {Caroline S.} and North, {Kari E.} and Reiner, {Alex P.} and Brendan Keating and Taylor, {Kira C.}",

year = "2014",

month = may,

doi = "10.1093/hmg/ddt626",

language = "English",

volume = "23",

pages = "2498--2510",

journal = "Human Molecular Genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "9",

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T1 - Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of european descent confirm known loci and reveal several novel associations

AU - Yoneyama, Sachiko

AU - Guo, Yiran

AU - Lanktree, Matthew B.

AU - Barnes, Michael R.

AU - Elbers, Clara C.

AU - Karczewski, Konrad J.

AU - Padmanabhan, Sandosh

AU - Bauer, Florianne

AU - Baumert, Jens

AU - Beitelshees, Amber

AU - Berenson, Gerald S.

AU - Boer, Jolanda M.A.

AU - Burke, Gregory

AU - Cade, Brian

AU - Chen, Wei

AU - Cooper-Dehoff, Rhonda M.

AU - Gaunt, Tom R.

AU - Gieger, Christian

AU - Gong, Yan

AU - Gorski, Mathias

AU - Heard-Costa, Nancy

AU - Johnson, Toby

AU - Lamonte, Michael J.

AU - Mcdonough, Caitrin

AU - Monda, Keri L.

AU - Onland-Moret, N. Charlotte

AU - Nelson, Christopher P.

AU - O'Connell, Jeffrey R.

AU - Ordovas, Jose

AU - Peter, Inga

AU - Peters, Annette

AU - Shaffer, Jonathan

AU - Shen, Haiqinq

AU - Smith, Erin

AU - Speilotes, Liz

AU - Thomas, Fridtjof

AU - Thorand, Barbara

AU - Verschuren, W. M.Monique

AU - Anand, Sonia S.

AU - Dominiczak, Anna

AU - Davidson, Karina W.

AU - Hegele, Robert A.

AU - Heid, Iris

AU - Hofker, Marten H.

AU - Huggins, Gordon S.

AU - Illig, Thomas

AU - Johnson, Julie A.

AU - Kirkland, Susan

AU - König, Wolfgang

AU - Langaee, Taimour Y.

AU - Mccaffery, Jeanne

AU - Melander, Olle

AU - Mitchell, Braxton D.

AU - Munroe, Patricia

AU - Murray, Sarah S.

AU - Papanicolaou, George

AU - Redline, Susan

AU - Reilly, Muredach

AU - Samani, Nilesh J.

AU - Schork, Nicholas J.

AU - Van Der Schouw, Yvonne T.

AU - Shimbo, Daichi

AU - Shuldiner, Alan R.

AU - Tobin, Martin D.

AU - Wijmenga, Cisca

AU - Yusuf, Salim

AU - Hakonarson, Hakon

AU - Lange, Leslie A.

AU - Demerath, Ellen W.

AU - Fox, Caroline S.

AU - North, Kari E.

AU - Reiner, Alex P.

AU - Keating, Brendan

AU - Taylor, Kira C.

PY - 2014/5

Y1 - 2014/5

N2 - Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ̃50 000 cosmopolitan tagged SNPs across̃2100cardiovascular-related genes. Eachtraitwasmodeled asa function of age, study siteandprincipal components to control for population stratification, andweconducted a fixed-effectsmeta-analysis. Nonewloci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 ×10-6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β±SE, 0.048±0.008, P=7.7×10-9) as was rs7302703-G in HOXC10 (β=0.044±0.008, P=2.9×10-7) and rs936108-C in PEMT (β-0.035±0.007, P=1.9×10-6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β=0.10±0.02, P=1.9×10-6) and rs1037575-A in ATBDB4 (β=0.046±0.01, P=2.2×10-6), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

AB - Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes ̃50 000 cosmopolitan tagged SNPs across̃2100cardiovascular-related genes. Eachtraitwasmodeled asa function of age, study siteandprincipal components to control for population stratification, andweconducted a fixed-effectsmeta-analysis. Nonewloci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 ×10-6). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (β±SE, 0.048±0.008, P=7.7×10-9) as was rs7302703-G in HOXC10 (β=0.044±0.008, P=2.9×10-7) and rs936108-C in PEMT (β-0.035±0.007, P=1.9×10-6). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (β=0.10±0.02, P=1.9×10-6) and rs1037575-A in ATBDB4 (β=0.046±0.01, P=2.2×10-6), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.

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Gene-centric meta-analyses for central adiposity traits in up to 57 412 individuals of european descent confirm known loci and reveal several novel associations

Resumen

ASJC Scopus Subject Areas

ODS de las Naciones Unidas

Acceder al documento

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Huella

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