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

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

In: Human Molecular Genetics, Vol. 23, No. 9, 2014, p. 2498-2510.

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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, Koenig, 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, no. 9, pp. 2498-2510. https://doi.org/10.1093/hmg/ddt626

APA

CBE

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, Koenig 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. 23(9):2498-2510. https://doi.org/10.1093/hmg/ddt626

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Author

Yoneyama, Sachiko ; Guo, Yiran ; Lanktree, Matthew B. ; Barnes, Michael R. ; Elbers, Clara C. ; Karczewski, Konrad J. ; Padmanabhan, Sandosh ; Bauer, Florianne ; Baumert, Jens ; Beitelshees, Amber ; Berenson, Gerald S. ; Boer, Jolanda M. A. ; Burke, Gregory ; Cade, Brian ; Chen, Wei ; Cooper-Dehoff, Rhonda M. ; Gaunt, Tom R. ; Gieger, Christian ; Gong, Yan ; Gorski, Mathias ; Heard-Costa, Nancy ; Johnson, Toby ; Lamonte, Michael J. ; Mcdonough, Caitrin ; Monda, Keri L. ; Onland-Moret, N. Charlotte ; Nelson, Christopher P. ; O'Connell, Jeffrey R. ; Ordovas, Jose ; Peter, Inga ; Peters, Annette ; Shaffer, Jonathan ; Shen, Haiqinq ; Smith, Erin ; Speilotes, Liz ; Thomas, Fridtjof ; Thorand, Barbara ; Verschuren, W. M. Monique ; Anand, Sonia S. ; Dominiczak, Anna ; Davidson, Karina W. ; Hegele, Robert A. ; Heid, Iris ; Hofker, Marten H. ; Huggins, Gordon S. ; Illig, Thomas ; Johnson, Julie A. ; Kirkland, Susan ; Koenig, Wolfgang ; Langaee, Taimour Y. ; Mccaffery, Jeanne ; Melander, Olle ; Mitchell, Braxton D. ; Munroe, Patricia ; Murray, Sarah S. ; Papanicolaou, George ; Redline, Susan ; Reilly, Muredach ; Samani, Nilesh J. ; Schork, Nicholas J. ; Van der Schouw, Yvonne T. ; Shimbo, Daichi ; Shuldiner, Alan R. ; Tobin, Martin D. ; Wijmenga, Cisca ; Yusuf, Salim ; Hakonarson, Hakon ; Lange, Leslie A. ; Demerath, Ellen W. ; Fox, Caroline S. ; North, Kari E. ; Reiner, Alex P. ; Keating, Brendan ; Taylor, Kira C. / 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. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 9. pp. 2498-2510.

RIS

TY - JOUR

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 - Koenig, 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

Y1 - 2014

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 NHLBIs Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 2080 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes 50 000 cosmopolitan tagged SNPs across 2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci 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 ( SE, 0.048 0.008, P 7.7 10(9)) as was rs7302703-G in HOXC10 ( 0.044 0.008, P 2.9 10(7)) and rs936108-C in PEMT ( 0.035 0.007, P 1.9 10(6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 ( 0.10 0.02, P 1.9 10(6)) and rs1037575-A in ATBDB4 ( 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 NHLBIs Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 2080 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes 50 000 cosmopolitan tagged SNPs across 2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci 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 ( SE, 0.048 0.008, P 7.7 10(9)) as was rs7302703-G in HOXC10 ( 0.044 0.008, P 2.9 10(7)) and rs936108-C in PEMT ( 0.035 0.007, P 1.9 10(6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 ( 0.10 0.02, P 1.9 10(6)) and rs1037575-A in ATBDB4 ( 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.

U2 - 10.1093/hmg/ddt626

DO - 10.1093/hmg/ddt626

M3 - Article

VL - 23

SP - 2498

EP - 2510

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 9

ER -