Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.

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Estrada, Karol (author)

Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.

Article/chapterEnglish2012

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2012-04-15
Springer Science and Business Media LLC,2012

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LIBRIS-ID:oai:gup.ub.gu.se/161420
https://gup.ub.gu.se/publication/161420URI
https://doi.org/10.1038/ng.2249DOI
https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-54103URI
https://lup.lub.lu.se/record/2809520URI
https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-176250URI

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Language:English

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Subject category:ref swepub-contenttype
Subject category:art swepub-publicationtype

Notes

Published online 15 April 2012
Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.

Subject headings and genre

MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Endokrinologi och diabetes hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Endocrinology and Diabetes hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin Ortopedi hsv//swe
MEDICAL AND HEALTH SCIENCES Clinical Medicine Orthopaedics hsv//eng
Bone Density
genetics
Computational Biology
European Continental Ancestry Group
Extracellular Matrix Proteins
genetics
Female
Femur Neck
physiopathology
Fractures
Bone
genetics
Gene Expression Profiling
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Glycoproteins
genetics
Humans
Intercellular Signaling Peptides and Proteins
genetics
Low Density Lipoprotein Receptor-Related Protein-5
genetics
Lumbar Vertebrae
physiopathology
Male
Mitochondrial Membrane Transport Proteins
genetics
Osteoporosis
genetics
Phosphoproteins
genetics
Polymorphism
Single Nucleotide
genetics
Quantitative Trait Loci
Risk Factors
Spectrin
genetics
genetik
Orthopaedics

Added entries (persons, corporate bodies, meetings, titles ...)

Styrkarsdottir, Unnur (author)
Evangelou, Evangelos (author)
Hsu, Yi-Hsiang (author)
Duncan, Emma L (author)
Ntzani, Evangelia E (author)
Oei, Ling (author)
Albagha, Omar M E (author)
Amin, Najaf (author)
Kemp, John P (author)
Koller, Daniel L (author)
Li, Guo (author)
Liu, Ching-Ti (author)
Minster, Ryan L (author)
Moayyeri, Alireza (author)
Vandenput, Liesbeth,1974Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xvanli (author)
Willner, Dana (author)
Xiao, Su-Mei (author)
Yerges-Armstrong, Laura M (author)
Zheng, Hou-Feng (author)
Alonso, Nerea (author)
Eriksson, JoelGothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xerjoe (author)
Kammerer, Candace M (author)
Kaptoge, Stephen K (author)
Leo, Paul J (author)
Thorleifsson, Gudmar (author)
Wilson, Scott G (author)
Wilson, James F (author)
Aalto, Ville (author)
Alen, Markku (author)
Aragaki, Aaron K (author)
Aspelund, Thor (author)
Center, Jacqueline R (author)
Dailiana, Zoe (author)
Duggan, David J (author)
Garcia, Melissa (author)
Garcia-Giralt, Natalia (author)
Giroux, Sylvie (author)
Hallmans, GöranUmeå universitet,Näringsforskning(Swepub:umu)goha0001 (author)
Hocking, Lynne J (author)
Husted, Lise Bjerre (author)
Jameson, Karen A (author)
Khusainova, Rita (author)
Kim, Ghi Su (author)
Kooperberg, Charles (author)
Koromila, Theodora (author)
Kruk, Marcin (author)
Laaksonen, Marika (author)
Lacroix, Andrea Z (author)
Lee, Seung Hun (author)
Leung, Ping C (author)
Lewis, Joshua R (author)
Masi, Laura (author)
Mencej-Bedrac, Simona (author)
Nguyen, Tuan V (author)
Nogues, Xavier (author)
Patel, Millan S (author)
Prezelj, Janez (author)
Rose, Lynda M (author)
Scollen, Serena (author)
Siggeirsdottir, Kristin (author)
Smith, Albert V (author)
Svensson, OlleUmeå universitet,Institutionen för kirurgisk och perioperativ vetenskap(Swepub:umu)olsv0001 (author)
Trompet, Stella (author)
Trummer, Olivia (author)
Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xmelda (author)
Woo, Jean (author)
Zhu, Kun (author)
Balcells, Susana (author)
Brandi, Maria Luisa (author)
Buckley, Brendan M (author)
Cheng, Sulin (author)
Christiansen, Claus (author)
Cooper, Cyrus (author)
Dedoussis, George (author)
Ford, Ian (author)
Frost, Morten (author)
Goltzman, David (author)
Gonzalez-Macias, Jesus (author)
Kähönen, Mika (author)
Karlsson, MagnusLund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups(Swepub:lu)orto-mka (author)
Khusnutdinova, Elza (author)
Koh, Jung-Min (author)
Kollia, Panagoula (author)
Langdahl, Bente Lomholt (author)
Leslie, William D (author)
Lips, Paul (author)
Ljunggren, ÖstenUppsala universitet,Institutionen för medicinska vetenskaper,Metabola bensjukdomar(Swepub:uu)osteljun (author)
Lorenc, Roman S (author)
Marc, Janja (author)
Mellström, Dan,1945Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xmelda (author)
Obermayer-Pietsch, Barbara (author)
Olmos, José M (author)
Pettersson-Kymmer, UlrikaUmeå universitet,Klinisk farmakologi(Swepub:umu)ulpe0007 (author)
Reid, David M (author)
Riancho, José A (author)
Ridker, Paul M (author)
Rousseau, François (author)
Slagboom, P Eline (author)
Tang, Nelson L S (author)
Urreizti, Roser (author)
Van Hul, Wim (author)
Viikari, Jorma (author)
Zarrabeitia, María T (author)
Aulchenko, Yurii S (author)
Castano-Betancourt, Martha (author)
Grundberg, Elin (author)
Herrera, Lizbeth (author)
Ingvarsson, Thorvaldur (author)
Johannsdottir, Hrefna (author)
Kwan, Tony (author)
Li, Rui (author)
Luben, Robert (author)
Medina-Gomez, Carolina (author)
Palsson, Stefan Th (author)
Reppe, Sjur (author)
Rotter, Jerome I (author)
Sigurdsson, Gunnar (author)
van Meurs, Joyce B J (author)
Verlaan, Dominique (author)
Williams, Frances M K (author)
Wood, Andrew R (author)
Zhou, Yanhua (author)
Gautvik, Kaare M (author)
Pastinen, Tomi (author)
Raychaudhuri, Soumya (author)
Cauley, Jane A (author)
Chasman, Daniel I (author)
Clark, Graeme R (author)
Cummings, Steven R (author)
Danoy, Patrick (author)
Dennison, Elaine M (author)
Eastell, Richard (author)
Eisman, John A (author)
Gudnason, Vilmundur (author)
Hofman, Albert (author)
Jackson, Rebecca D (author)
Jones, Graeme (author)
Jukema, J Wouter (author)
Khaw, Kay-Tee (author)
Lehtimäki, Terho (author)
Liu, Yongmei (author)
Lorentzon, Mattias,1970Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xlomat (author)
McCloskey, Eugene (author)
Mitchell, Braxton D (author)
Nandakumar, Kannabiran (author)
Nicholson, Geoffrey C (author)
Oostra, Ben A (author)
Peacock, Munro (author)
Pols, Huibert A P (author)
Prince, Richard L (author)
Raitakari, Olli (author)
Reid, Ian R (author)
Robbins, John (author)
Sambrook, Philip N (author)
Sham, Pak Chung (author)
Shuldiner, Alan R (author)
Tylavsky, Frances A (author)
van Duijn, Cornelia M (author)
Wareham, Nick J (author)
Cupples, L Adrienne (author)
Econs, Michael J (author)
Evans, David M (author)
Harris, Tamara B (author)
Kung, Annie Wai Chee (author)
Psaty, Bruce M (author)
Reeve, Jonathan (author)
Spector, Timothy D (author)
Streeten, Elizabeth A (author)
Zillikens, M Carola (author)
Thorsteinsdottir, Unnur (author)
Ohlsson, Claes,1965Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research(Swepub:gu)xohlcl (author)
Karasik, David (author)
Richards, J Brent (author)
Brown, Matthew A (author)
Stefansson, Kari (author)
Uitterlinden, Andre G (author)
Ralston, Stuart H (author)
Ioannidis, John P A (author)
Kiel, Douglas P (author)
Rivadeneira, Fernando (author)
Göteborgs universitetCentre for Bone and Arthritis Research (creator_code:org_t)

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In:Nature genetics: Springer Science and Business Media LLC44:5, s. 491-5011546-17181061-4036

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By the author/editor: Estrada, Karol; Styrkarsdottir, ...; Evangelou, Evang ...; Hsu, Yi-Hsiang; Duncan, Emma L; Ntzani, Evangeli ...; show more...; Oei, Ling; Albagha, Omar M ...; Amin, Najaf; Kemp, John P; Koller, Daniel L; Li, Guo; Liu, Ching-Ti; Minster, Ryan L; Moayyeri, Alirez ...; Vandenput, Liesb ...; Willner, Dana; Xiao, Su-Mei; Yerges-Armstrong ...; Zheng, Hou-Feng; Alonso, Nerea; Eriksson, Joel; Kammerer, Candac ...; Kaptoge, Stephen ...; Leo, Paul J; Thorleifsson, Gu ...; Wilson, Scott G; Wilson, James F; Aalto, Ville; Alen, Markku; Aragaki, Aaron K; Aspelund, Thor; Center, Jacqueli ...; Dailiana, Zoe; Duggan, David J; Garcia, Melissa; Garcia-Giralt, N ...; Giroux, Sylvie; Hallmans, Göran; Hocking, Lynne J; Husted, Lise Bje ...; Jameson, Karen A; Khusainova, Rita; Kim, Ghi Su; Kooperberg, Char ...; Koromila, Theodo ...; Kruk, Marcin; Laaksonen, Marik ...; Lacroix, Andrea ...; Lee, Seung Hun; Leung, Ping C; Lewis, Joshua R; Masi, Laura; Mencej-Bedrac, S ...; Nguyen, Tuan V; Nogues, Xavier; Patel, Millan S; Prezelj, Janez; Rose, Lynda M; Scollen, Serena; Siggeirsdottir, ...; Smith, Albert V; Svensson, Olle; Trompet, Stella; Trummer, Olivia; Mellström, Dan, ...; Woo, Jean; Zhu, Kun; Balcells, Susana; Brandi, Maria Lu ...; Buckley, Brendan ...; Cheng, Sulin; Christiansen, Cl ...; Cooper, Cyrus; Dedoussis, Georg ...; Ford, Ian; Frost, Morten; Goltzman, David; Gonzalez-Macias, ...; Kähönen, Mika; Karlsson, Magnus; Khusnutdinova, E ...; Koh, Jung-Min; Kollia, Panagoul ...; Langdahl, Bente ...; Leslie, William ...; Lips, Paul; Ljunggren, Östen; Lorenc, Roman S; Marc, Janja; Obermayer-Pietsc ...; Olmos, José M; Pettersson-Kymme ...; Reid, David M; Riancho, José A; Ridker, Paul M; Rousseau, Franço ...; Slagboom, P Elin ...; Tang, Nelson L S; Urreizti, Roser; Van Hul, Wim; Viikari, Jorma; Zarrabeitia, Mar ...; Aulchenko, Yurii ...; Castano-Betancou ...; Grundberg, Elin; Herrera, Lizbeth; Ingvarsson, Thor ...; Johannsdottir, H ...; Kwan, Tony; Li, Rui; Luben, Robert; Medina-Gomez, Ca ...; Palsson, Stefan ...; Reppe, Sjur; Rotter, Jerome I; Sigurdsson, Gunn ...; van Meurs, Joyce ...; Verlaan, Dominiq ...; Williams, France ...; Wood, Andrew R; Zhou, Yanhua; Gautvik, Kaare M; Pastinen, Tomi; Raychaudhuri, So ...; Cauley, Jane A; Chasman, Daniel ...; Clark, Graeme R; Cummings, Steven ...; Danoy, Patrick; Dennison, Elaine ...; Eastell, Richard; Eisman, John A; Gudnason, Vilmun ...; Hofman, Albert; Jackson, Rebecca ...; Jones, Graeme; Jukema, J Wouter; Khaw, Kay-Tee; Lehtimäki, Terho; Liu, Yongmei; Lorentzon, Matti ...; McCloskey, Eugen ...; Mitchell, Braxto ...; Nandakumar, Kann ...; Nicholson, Geoff ...; Oostra, Ben A; Peacock, Munro; Pols, Huibert A ...; Prince, Richard ...; Raitakari, Olli; Reid, Ian R; Robbins, John; Sambrook, Philip ...; Sham, Pak Chung; Shuldiner, Alan ...; Tylavsky, France ...; van Duijn, Corne ...; Wareham, Nick J; Cupples, L Adrie ...; Econs, Michael J; Evans, David M; Harris, Tamara B; Kung, Annie Wai ...; Psaty, Bruce M; Reeve, Jonathan; Spector, Timothy ...; Streeten, Elizab ...; Zillikens, M Car ...; Thorsteinsdottir ...; Ohlsson, Claes, ...; Karasik, David; Richards, J Bren ...; Brown, Matthew A; Stefansson, Kari; Uitterlinden, An ...; Ralston, Stuart ...; Ioannidis, John ...; Kiel, Douglas P; Rivadeneira, Fer ...; show less...

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