Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

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Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. / Medina-Gomez, Carolina; Kemp, John P; Dimou, Niki L; Kreiner, Eskil; Chesi, Alessandra; Zemel, Babette S; Bønnelykke, Klaus; Boer, Cindy G; Ahluwalia, Tarunveer S; Bisgaard, Hans; Evangelou, Evangelos; Heppe, Denise H M; Bonewald, Lynda F; Gorski, Jeffrey P; Ghanbari, Mohsen; Demissie, Serkalem; Duque, Gustavo; Maurano, Matthew T; Kiel, Douglas P; Hsu, Yi-Hsiang; C J van der Eerden, Bram; Ackert-Bicknell, Cheryl; Reppe, Sjur; Gautvik, Kaare M; Raastad, Truls; Karasik, David; van de Peppel, Jeroen; Jaddoe, Vincent W V; Uitterlinden, André G; Tobias, Jonathan H; Grant, Struan F A; Bagos, Pantelis G; Evans, David M; Rivadeneira, Fernando.

In: Nature Communications, Vol. 8, 121, 2017.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Medina-Gomez, C, Kemp, JP, Dimou, NL, Kreiner, E, Chesi, A, Zemel, BS, Bønnelykke, K, Boer, CG, Ahluwalia, TS, Bisgaard, H, Evangelou, E, Heppe, DHM, Bonewald, LF, Gorski, JP, Ghanbari, M, Demissie, S, Duque, G, Maurano, MT, Kiel, DP, Hsu, Y-H, C J van der Eerden, B, Ackert-Bicknell, C, Reppe, S, Gautvik, KM, Raastad, T, Karasik, D, van de Peppel, J, Jaddoe, VWV, Uitterlinden, AG, Tobias, JH, Grant, SFA, Bagos, PG, Evans, DM & Rivadeneira, F 2017, 'Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus', Nature Communications, vol. 8, 121. https://doi.org/10.1038/s41467-017-00108-3

APA

Medina-Gomez, C., Kemp, J. P., Dimou, N. L., Kreiner, E., Chesi, A., Zemel, B. S., Bønnelykke, K., Boer, C. G., Ahluwalia, T. S., Bisgaard, H., Evangelou, E., Heppe, D. H. M., Bonewald, L. F., Gorski, J. P., Ghanbari, M., Demissie, S., Duque, G., Maurano, M. T., Kiel, D. P., ... Rivadeneira, F. (2017). Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. Nature Communications, 8, [121]. https://doi.org/10.1038/s41467-017-00108-3

Vancouver

Medina-Gomez C, Kemp JP, Dimou NL, Kreiner E, Chesi A, Zemel BS et al. Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. Nature Communications. 2017;8. 121. https://doi.org/10.1038/s41467-017-00108-3

Author

Medina-Gomez, Carolina ; Kemp, John P ; Dimou, Niki L ; Kreiner, Eskil ; Chesi, Alessandra ; Zemel, Babette S ; Bønnelykke, Klaus ; Boer, Cindy G ; Ahluwalia, Tarunveer S ; Bisgaard, Hans ; Evangelou, Evangelos ; Heppe, Denise H M ; Bonewald, Lynda F ; Gorski, Jeffrey P ; Ghanbari, Mohsen ; Demissie, Serkalem ; Duque, Gustavo ; Maurano, Matthew T ; Kiel, Douglas P ; Hsu, Yi-Hsiang ; C J van der Eerden, Bram ; Ackert-Bicknell, Cheryl ; Reppe, Sjur ; Gautvik, Kaare M ; Raastad, Truls ; Karasik, David ; van de Peppel, Jeroen ; Jaddoe, Vincent W V ; Uitterlinden, André G ; Tobias, Jonathan H ; Grant, Struan F A ; Bagos, Pantelis G ; Evans, David M ; Rivadeneira, Fernando. / Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus. In: Nature Communications. 2017 ; Vol. 8.

Bibtex

@article{16f6545259b94ff09833654d88b1f3d3,

title = "Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus",

abstract = "Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.",

keywords = "Body Weight, Bone Density, Carrier Proteins/genetics, Child, Female, Gene Expression, Genetic Pleiotropy, Genome-Wide Association Study/methods, Humans, Male, Meta-Analysis as Topic, Multivariate Analysis, Musculoskeletal Development/genetics, Polymorphism, Single Nucleotide, Quantitative Trait Loci/genetics, Sterol Regulatory Element Binding Protein 1/genetics",

author = "Carolina Medina-Gomez and Kemp, {John P} and Dimou, {Niki L} and Eskil Kreiner and Alessandra Chesi and Zemel, {Babette S} and Klaus B{\o}nnelykke and Boer, {Cindy G} and Ahluwalia, {Tarunveer S} and Hans Bisgaard and Evangelos Evangelou and Heppe, {Denise H M} and Bonewald, {Lynda F} and Gorski, {Jeffrey P} and Mohsen Ghanbari and Serkalem Demissie and Gustavo Duque and Maurano, {Matthew T} and Kiel, {Douglas P} and Yi-Hsiang Hsu and {C J van der Eerden}, Bram and Cheryl Ackert-Bicknell and Sjur Reppe and Gautvik, {Kaare M} and Truls Raastad and David Karasik and {van de Peppel}, Jeroen and Jaddoe, {Vincent W V} and Uitterlinden, {Andr{\'e} G} and Tobias, {Jonathan H} and Grant, {Struan F A} and Bagos, {Pantelis G} and Evans, {David M} and Fernando Rivadeneira",

year = "2017",

doi = "10.1038/s41467-017-00108-3",

language = "English",

volume = "8",

journal = "Nature Communications",

issn = "2041-1723",

publisher = "nature publishing group",

}

RIS

TY - JOUR

T1 - Bivariate genome-wide association meta-analysis of pediatric musculoskeletal traits reveals pleiotropic effects at the SREBF1/TOM1L2 locus

AU - Medina-Gomez, Carolina

AU - Kemp, John P

AU - Dimou, Niki L

AU - Kreiner, Eskil

AU - Chesi, Alessandra

AU - Zemel, Babette S

AU - Bønnelykke, Klaus

AU - Boer, Cindy G

AU - Ahluwalia, Tarunveer S

AU - Bisgaard, Hans

AU - Evangelou, Evangelos

AU - Heppe, Denise H M

AU - Bonewald, Lynda F

AU - Gorski, Jeffrey P

AU - Ghanbari, Mohsen

AU - Demissie, Serkalem

AU - Duque, Gustavo

AU - Maurano, Matthew T

AU - Kiel, Douglas P

AU - Hsu, Yi-Hsiang

AU - C J van der Eerden, Bram

AU - Ackert-Bicknell, Cheryl

AU - Reppe, Sjur

AU - Gautvik, Kaare M

AU - Raastad, Truls

AU - Karasik, David

AU - van de Peppel, Jeroen

AU - Jaddoe, Vincent W V

AU - Uitterlinden, André G

AU - Tobias, Jonathan H

AU - Grant, Struan F A

AU - Bagos, Pantelis G

AU - Evans, David M

AU - Rivadeneira, Fernando

PY - 2017

Y1 - 2017

N2 - Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.

AB - Bone mineral density is known to be a heritable, polygenic trait whereas genetic variants contributing to lean mass variation remain largely unknown. We estimated the shared SNP heritability and performed a bivariate GWAS meta-analysis of total-body lean mass (TB-LM) and total-body less head bone mineral density (TBLH-BMD) regions in 10,414 children. The estimated SNP heritability is 43% (95% CI: 34-52%) for TBLH-BMD, and 39% (95% CI: 30-48%) for TB-LM, with a shared genetic component of 43% (95% CI: 29-56%). We identify variants with pleiotropic effects in eight loci, including seven established bone mineral density loci: WNT4, GALNT3, MEPE, CPED1/WNT16, TNFSF11, RIN3, and PPP6R3/LRP5. Variants in the TOM1L2/SREBF1 locus exert opposing effects TB-LM and TBLH-BMD, and have a stronger association with the former trait. We show that SREBF1 is expressed in murine and human osteoblasts, as well as in human muscle tissue. This is the first bivariate GWAS meta-analysis to demonstrate genetic factors with pleiotropic effects on bone mineral density and lean mass.Bone mineral density and lean skeletal mass are heritable traits. Here, Medina-Gomez and colleagues perform bivariate GWAS analyses of total body lean mass and bone mass density in children, and show genetic loci with pleiotropic effects on both traits.

KW - Body Weight

KW - Bone Density

KW - Carrier Proteins/genetics

KW - Child

KW - Female

KW - Gene Expression

KW - Genetic Pleiotropy

KW - Genome-Wide Association Study/methods

KW - Humans

KW - Male

KW - Meta-Analysis as Topic

KW - Multivariate Analysis

KW - Musculoskeletal Development/genetics

KW - Polymorphism, Single Nucleotide

KW - Quantitative Trait Loci/genetics

KW - Sterol Regulatory Element Binding Protein 1/genetics

U2 - 10.1038/s41467-017-00108-3

DO - 10.1038/s41467-017-00108-3

M3 - Journal article

C2 - 28743860

VL - 8

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

M1 - 121

ER -

ID: 194769723