Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture

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001		oai:DiVA.org:uu-269270
003		SwePub
008		151215s2015 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
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024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-2692702 URI
024	7	a https://doi.org/10.1038/nature148782 DOI
024	7	a https://lup.lub.lu.se/record/80421892 URI
024	7	a https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1122722 URI
024	7	a https://gup.ub.gu.se/publication/2262472 URI
040		a (SwePub)uud (SwePub)lud (SwePub)umud (SwePub)gu
041		a engb eng
042		9 SwePub
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100	1	a Zheng, Hou-Fengu McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.4 aut
245	1 0	a Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
264		c 2015-09-14
264	1	b Springer Science and Business Media LLC,c 2015
338		a print2 rdacarrier
520		a The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Hälsovetenskapx Näringslära0 (SwePub)303042 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Health Sciencesx Nutrition and Dietetics0 (SwePub)303042 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Hälsovetenskap0 (SwePub)3032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Health Sciences0 (SwePub)3032 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Ortopedi0 (SwePub)302112 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Orthopaedics0 (SwePub)302112 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Hälsovetenskapx Folkhälsovetenskap, global hälsa, socialmedicin och epidemiologi0 (SwePub)303022 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Health Sciencesx Public Health, Global Health, Social Medicine and Epidemiology0 (SwePub)303022 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Endokrinologi och diabetes0 (SwePub)302052 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Endocrinology and Diabetes0 (SwePub)302052 hsv//eng
700	1	a Forgetta, Vincenzou McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.4 aut
700	1	a Hsu, Yi-Hsiangu Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA.4 aut
700	1	a Estrada, Karolu Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA.;Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Massachusetts Gen Hosp, Analyt & Translat Genet Unit, Boston, MA 02114 USA.4 aut
700	1	a Rosello-Diez, Albertou Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.4 aut
700	1	a Leo, Paul J.u Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.4 aut
700	1	a Dahia, Chitra L.u Weill Cornell Med Coll, Dept Cell & Dev Biol, New York, NY 10065 USA.;Hosp Special Surg, Tissue Engn Regenerat & Repair Program, New York, NY 10021 USA.4 aut
700	1	a Park-Min, Kyung Hyunu Hosp Special Surg, Rheumatol Div, New York, NY 10021 USA.4 aut
700	1	a Tobias, Jonathan H.u Univ Bristol, Sch Clin Sci, Bristol BS10 5NB, Avon, England.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.4 aut
700	1	a Kooperberg, Charlesu Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.4 aut
700	1	a Kleinman, Aaronu 23andMe, Res Dept, Mountain View, CA 94041 USA.4 aut
700	1	a Styrkarsdottir, Unnuru deCODE Genet, Dept Populat Genom, IS-101 Reykjavik, Iceland.4 aut
700	1	a Liu, Ching-Tiu Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.4 aut
700	1	a Uggla, Charlottau Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research4 aut
700	1	a Evans, Daniel S.u Calif Pacific Med Ctr, Res Inst, San Francisco, CA 94158 USA.4 aut
700	1	a Nielson, Carrie M.u Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Bone Mineral Unit, Portland, OR 97239 USA.,Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.4 aut
700	1	a Walter, Klaudiau Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.4 aut
700	1	a Pettersson-Kymmer, Ulrikau Umeå universitet,Näringsforskning,Farmakologi,Umea Univ, Dept Pharmacol, S-90187 Umea, Sweden.;Umea Univ, Dept Clin Neurosci, S-90187 Umea, Sweden.;Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden.4 aut0 (Swepub:umu)ulpe0007
700	1	a McCarthy, Shaneu Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.4 aut
700	1	a Eriksson, Joelu Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research4 aut0 (Swepub:gu)xerjoe
700	1	a Kwan, Tonyu McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.4 aut
700	1	a Jhamai, Milau Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.4 aut
700	1	a Trajanoska, Katerinau Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.4 aut
700	1	a Memari, Yasinu Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.4 aut
700	1	a Min, Josineu Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.4 aut
700	1	a Huang, Jieu Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.4 aut
700	1	a Danecek, Petru Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.4 aut
700	1	a Wilmot, Bethu Oregon Hlth & Sci Univ, Oregon Clin & Translat Res Inst, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Dept Med & Clin Informat, Portland, OR 97239 USA.4 aut
700	1	a Li, Ruiu McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.4 aut
700	1	a Chou, Wen-Chiu Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.4 aut
700	1	a Mokry, Lauren E.u McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.4 aut
700	1	a Moayyeri, Alirezau UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.4 aut
700	1	a Claussnitzer, Melinau Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA.;Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA.,Wageningen Univ, Dept Human Nutr, NL-6700 EV Wageningen, Netherlands.4 aut
700	1	a Cheng, Chia-Hou Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.4 aut
700	1	a Cheung, Warrenu McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.4 aut
700	1	a Medina-Gomez, Carolinau Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands.4 aut
700	1	a Ge, Bingu McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.4 aut
700	1	a Chen, Shu-Huangu McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.4 aut
700	1	a Choi, Kwangbomu Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14642 USA.4 aut
700	1	a Oei, Lingu Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands.4 aut
700	1	a Fraser, Jamesu McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.;McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada.4 aut
700	1	a Kraaij, Robertu Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands.4 aut
700	1	a Hibbs, Matthew A.u Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14642 USA.;Trinity Univ, Dept Comp Sci, San Antonio, TX 78212 USA.4 aut
700	1	a Gregson, Celia L.u Univ Bristol, Musculoskeletal Res Unit, Bristol BS10 5NB, Avon, England.4 aut
700	1	a Paquette, Denisu McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.;McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada.4 aut
700	1	a Hofman, Albertu Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands.4 aut
700	1	a Wibom, Carlu Umeå universitet,Institutionen för strålningsvetenskaper,Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden.4 aut0 (Swepub:umu)caewim02
700	1	a Tranah, Gregory J.u Oregon Hlth & Sci Univ, Dept Publ Hlth & Prevent Med, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Bone Mineral Unit, Portland, OR 97239 USA.4 aut
700	1	a Marshall, Mhairiu Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.,Vrije Univ Amsterdam, Med Ctr, Dept Epidemiol & Biostat, NL-1007 MB Amsterdam, Netherlands.;Vrije Univ Amsterdam, Med Ctr, EMGO Inst Hlth & Care Res, NL-1007 MB Amsterdam, Netherlands.,Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.,Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands.,Univ Malta, Dept Appl Biomed Sci, Fac Hlth Sci, MSD-2080 Msida, Malta.,Univ Cantabria, Dept Med & Psychiat, Santander 39011, Spain.;Hosp UM Valdecilla IDIVAL, Dept Internal Med, Santander 39008, Spain.,Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.,McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Gerald Bronfman Ctr, Dept Oncol, Montreal, PQ H2W 1S6, Canada.4 aut
700	1	a Gardiner, Brooke B.u Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.4 aut
700	1	a Cremin, Katieu Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.4 aut
700	1	a Auer, Paulu Univ Wisconsin, Sch Publ Hlth, Milwaukee, WI 53726 USA.4 aut
700	1	a Hsu, Liu Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.4 aut
700	1	a Ring, Sueu Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England.4 aut
700	1	a Tung, Joyce Y.u 23andMe, Res Dept, Mountain View, CA 94041 USA.4 aut
700	1	a Thorleifsson, Gudmaru deCODE Genet, Dept Stat, IS-101 Reykjavik, Iceland.4 aut
700	1	a Enneman, Anke W.u Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.4 aut
700	1	a Mellström, Dan,d 1945u Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för samhällsmedicin och folkhälsa,Institute of Medicine, School of Public Health and Community Medicine4 aut0 (Swepub:gu)xmelda
700	1	a Garg, Gauravu Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands.,Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden.4 aut0 (Swepub:lu)med-ggr
700	1	a van der Velde, Nathalieu Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Acad Med Ctr, Sect Geriatr, Dept Internal Med, NL-1105 Amsterdam, Netherlands.4 aut
700	1	a Melin, Beatriceu Umeå universitet,Institutionen för strålningsvetenskaper,Umea Univ, Dept Radiat Sci, S-90187 Umea, Sweden.4 aut0 (Swepub:umu)bema0010
700	1	a Kemp, John P.u Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.4 aut
700	1	a Christiansen, Clausu Nord Biosci, DK-2730 Herlev, Denmark.4 aut
700	1	a Sayers, Adrianu Univ Bristol, Musculoskeletal Res Unit, Bristol BS10 5NB, Avon, England.4 aut
700	1	a Zhou, Yanhuau Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.4 aut
700	1	a Calderari, Sophieu INSERM, UMRS 1138, Cordeliers Res Ctr, F-75006 Paris, France.;Univ Paris 06, Inst Cardiometab & Nutr, F-75013 Paris, France.4 aut
700	1	a van Rooij, Jeroenu Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands.4 aut
700	1	a Carlson, Chrisu Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.4 aut
700	1	a Peters, Ulrikeu Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.4 aut
700	1	a Berlivet, Soiziku McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.;McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada.4 aut
700	1	a Dostie, Joseeu McGill Univ, Dept Biochem, Montreal, PQ H3G 1Y6, Canada.;McGill Univ, Goodman Canc Res Ctr, Montreal, PQ H3G 1Y6, Canada.4 aut
700	1	a Uitterlinden, Andre G.u Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands.4 aut
700	1	a Williams, Stephen R.u Univ Virginia, Ctr Publ Hlth Genom, Dept Med, Charlottesville, VA 22908 USA.;Univ Virginia, Ctr Publ Hlth Genom, Dept Cardiovasc Med, Charlottesville, VA 22908 USA.4 aut
700	1	a Farber, Charlesu Univ Virginia, Ctr Publ Hlth Genom, Dept Med, Charlottesville, VA 22908 USA.;Univ Virginia, Ctr Publ Hlth Genom, Dept Cardiovasc Med, Charlottesville, VA 22908 USA.4 aut
700	1	a Grinberg, Danielu Univ Barcelona, Dept Genet, E-08028 Barcelona, Spain.;Ctr Biomed Network Res Rare Dis CIBERER, U720, Barcelona 28029, Spain.;Univ Barcelona, Inst Biomed, Dept Human Mol Genet, E-08028 Barcelona, Spain.4 aut
700	1	a LaCroix, Andrea Z.u Univ Calif San Diego, Womens Hlth Ctr Excellence Family Med & Publ Hlth, San Diego, CA 92103 USA.4 aut
700	1	a Haessler, Jeffu Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA.4 aut
700	1	a Chasman, Daniel I.u Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.4 aut
700	1	a Giulianini, Francou Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.4 aut
700	1	a Rose, Lynda M.u Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.4 aut
700	1	a Ridker, Paul M.u Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02215 USA.4 aut
700	1	a Eisman, John A.u Garvan Inst Med Res, Osteoporosis & Bone Biol Program, Sydney, NSW 2010, Australia.;Univ Notre Dame Australia, Sch Med Sydney, Sydney, NSW 6959, Australia.;NSW Univ, St Vincents Hosp, Sydney, NSW 2010, Australia.;NSW Univ, Sch Clin, Sydney, NSW 2010, Australia.4 aut
700	1	a Nguyen, Tuan V.u Garvan Inst Med Res, Osteoporosis & Bone Biol Program, Sydney, NSW 2010, Australia.;NSW Univ, St Vincents Hosp, Sydney, NSW 2010, Australia.;NSW Univ, Sch Clin, Sydney, NSW 2010, Australia.4 aut
700	1	a Center, Jacqueline R.u Garvan Inst Med Res, Osteoporosis & Bone Biol Program, Sydney, NSW 2010, Australia.;NSW Univ, St Vincents Hosp, Sydney, NSW 2010, Australia.;NSW Univ, Sch Clin, Sydney, NSW 2010, Australia.4 aut
700	1	a Nogues, Xavieru Univ Virginia, Ctr Publ Hlth Genom, Dept Med, Charlottesville, VA 22908 USA.;Univ Virginia, Ctr Publ Hlth Genom, Dept Cardiovasc Med, Charlottesville, VA 22908 USA.;Inst Hosp Mar Invest Med, Musculoskeletal Res Grp, Barcelona 08003, Spain.;Univ Autonoma Barcelona, Hosp Mar, Dept Internal Med, E-08193 Barcelona, Spain.4 aut
700	1	a Garcia-Giralt, Nataliau Inst Hosp Mar Invest Med, Musculoskeletal Res Grp, Barcelona 08003, Spain.;Inst Hlth Carlos III, Cooperat Res Network Aging & Fragil RETICEF, Madrid 28029, Spain.4 aut
700	1	a Launer, Lenore L.u NIA, Neuroepidemiol Sect, NIH, Bethesda, MD 20892 USA.,Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.;Univ Western Australia, Dept Med, Perth, WA 6009, Australia.,Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus C, Denmark.,Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.,Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14642 USA.,Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.,Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.;Royal Brisbane & Womens Hosp, Dept Diabet & Endocrinol, Brisbane, Qld 4029, Australia.4 aut
700	1	a Gudnason, Vilmunderu Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.4 aut
700	1	a Mellstrom, Danu Univ Gothenburg, Ctr Bone & Arthrit Res, Dept Internal Med & Clin Nutr, Inst Med,Sahlgrenska Acad, S-41345 Gothenburg, Sweden.4 aut
700	1	a Vandenput, Liesbeth,d 1974u Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research4 aut0 (Swepub:gu)xvanli
700	1	a Amin, Najafu Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands.4 aut
700	1	a van Duijn, Cornelia M.u Erasmus MC, Dept Epidemiol, Genet Epidemiol Unit, NL-3000 CA Rotterdam, Netherlands.4 aut
700	1	a Karlsson, Magnusu Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skane Univ Hosp, Dept Orthopaed, S-20502 Malmo, Sweden.4 aut0 (Swepub:lu)orto-mka
700	1	a Ljunggren, Östenu Uppsala universitet,Endokrinologi och mineralmetabolism4 aut0 (Swepub:uu)osteljun
700	1	a Svensson, Olleu Umeå universitet,Institutionen för kirurgisk och perioperativ vetenskap,Umea Univ, Dept Surg & Perioperat Sci, S-90185 Umea, Sweden.4 aut0 (Swepub:umu)olsv0001
700	1	a Hallmans, Göranu Umeå universitet,Näringsforskning,Enheten för biobanksforskning,Umea Univ, Dept Publ Hlth & Clin Med, SE-90187 Umea, Sweden.4 aut0 (Swepub:umu)goha0001
700	1	a Rousseau, Francoisu Univ Laval, Dept Mol Biol Med Biochem & Pathol, Quebec City, PQ G1V 0A6, Canada.;CHU Quebec, Ctr Rech, Axe Sante Populat & Prat Optimales Sante, Quebec City, PQ G1V 4G2, Canada.4 aut
700	1	a Giroux, Sylvieu CHU Quebec, Ctr Rech, Axe Sante Populat & Prat Optimales Sante, Quebec City, PQ G1V 4G2, Canada.4 aut
700	1	a Bussiere, Johanneu CHU Quebec, Ctr Rech, Axe Sante Populat & Prat Optimales Sante, Quebec City, PQ G1V 4G2, Canada.,Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.4 aut
700	1	a Arp, Pascal P.u Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.4 aut
700	1	a Koromani, Fjordau Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.4 aut
700	1	a Prince, Richard L.u Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.;Univ Western Australia, Dept Med, Perth, WA 6009, Australia.4 aut
700	1	a Lewis, Joshua R.u Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.;Univ Western Australia, Dept Med, Perth, WA 6009, Australia.4 aut
700	1	a Langdahl, Bente L.u Aarhus Univ Hosp, Dept Endocrinol & Internal Med, DK-8000 Aarhus C, Denmark.4 aut
700	1	a Hermann, A. Pernilleu Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense C, Denmark.4 aut
700	1	a Jensen, Jens-Erik B.u Hvidovre Univ Hosp, Dept Endocrinol, DK-2650 Hvidovre, Denmark.4 aut
700	1	a Kaptoge, Stephenu UCL, Farr Inst Hlth Informat Res, London NW1 2DA, England.4 aut
700	1	a Khaw, Kay-Teeu Univ Cambridge, Clin Gerontol Unit, Cambridge CB2 2QQ, England.4 aut
700	1	a Reeve, Jonathanu Univ Cambridge, Med & Publ Hlth & Primary Care, Cambridge CB1 8RN, England.;Univ Oxford, Botnar Res Ctr, Inst Musculoskeletal Sci, Oxford OX3 7LD, England.4 aut
700	1	a Formosa, Melissa M.u Univ Malta, Dept Appl Biomed Sci, Fac Hlth Sci, MSD-2080 Msida, Malta.4 aut
700	1	a Xuereb-Anastasi, Angelau Univ Malta, Dept Appl Biomed Sci, Fac Hlth Sci, MSD-2080 Msida, Malta.4 aut
700	1	a Åkesson, Kristinau Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Skane Univ Hosp, Dept Orthopaed, S-20502 Malmo, Sweden.;Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden.4 aut0 (Swepub:lu)orto-kak
700	1	a McGuigan, Fionau Lund University,Lunds universitet,Ortopedi - klinisk och molekylär osteoporosforskning,Forskargrupper vid Lunds universitet,Orthopedics - Clinical and Molecular Osteoporosis Research,Lund University Research Groups,Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden.4 aut0 (Swepub:lu)med-fam
700	1	a Garg, Gauravu Lund Univ, Clin & Mol Osteoporosis Res Unit, Dept Clin Sci Malmo, S-20502 Lund, Sweden.4 aut
700	1	a Olmos, Jose M.u Univ Cantabria, Dept Med & Psychiat, Santander 39011, Spain.;Hosp UM Valdecilla IDIVAL, Dept Internal Med, Santander 39008, Spain.4 aut
700	1	a Zarrabeitia, Maria T.u Univ Cantabria, Dept Legal Med, Santander 39011, Spain.4 aut
700	1	a Riancho, Jose A.u Univ Cantabria, Dept Med & Psychiat, Santander 39011, Spain.;Hosp UM Valdecilla IDIVAL, Dept Internal Med, Santander 39008, Spain.4 aut
700	1	a Ralston, Stuart H.u Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland.4 aut
700	1	a Alonso, Nereau Univ Edinburgh, Inst Genet & Mol Med, Western Gen Hosp, Ctr Genom & Expt Med, Edinburgh EH4 2XU, Midlothian, Scotland.4 aut
700	1	a Jiang, Xiu Univ Connecticut, Ctr Hlth, Coll Dent Med, Dept Reconstruct Sci, Farmington, CT 06030 USA.4 aut
700	1	a Goltzman, Davidu McGill Univ, Dept Med & Physiol, Montreal, PQ H4A 3J1, Canada.4 aut
700	1	a Pastinen, Tomiu McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.4 aut
700	1	a Grundberg, Elinu McGill Univ, Montreal, PQ H3A 0G1, Canada.;Genome Quebec Innovat Ctr, Montreal, PQ H3A 0G1, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.4 aut
700	1	a Gauguier, Dominiqueu INSERM, UMRS 1138, Cordeliers Res Ctr, F-75006 Paris, France.;Univ Paris 06, Inst Cardiometab & Nutr, F-75013 Paris, France.4 aut
700	1	a Orwoll, Eric S.u Oregon Hlth & Sci Univ, Bone Mineral Unit, Portland, OR 97239 USA.;Oregon Hlth & Sci Univ, Dept Med, Portland, OR 97239 USA.4 aut
700	1	a Karasik, Davidu Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Bar Ilan Univ, Fac Med Galilee, IL-13010 Safed, Israel.4 aut
700	1	a Davey-Smith, Georgeu Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.4 aut
700	1	a Smith, Albert V.u Iceland Heart Assoc, IS-201 Kopavogur, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.4 aut
700	1	a Siggeirsdottir, Kristinu Iceland Heart Assoc, IS-201 Kopavogur, Iceland.4 aut
700	1	a Harris, Tamara B.u NIA, Lab Epidemiol, NIH, Bethesda, MD 20892 USA.4 aut
700	1	a Zillikens, M. Carolau Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.4 aut
700	1	a van Meurs, Joyce B. J.u Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.4 aut
700	1	a Thorsteinsdottir, Unnuru deCODE Genet, Dept Populat Genom, IS-101 Reykjavik, Iceland.;Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.4 aut
700	1	a Maurano, Matthew T.u Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA.4 aut
700	1	a Timpson, Nicholas J.u Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.4 aut
700	1	a Soranzo, Nicoleu Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.4 aut
700	1	a Durbin, Richardu Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England.4 aut
700	1	a Wilson, ScottG.u Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.;Sir Charles Gairdner Hosp, Dept Endocrinol & Diabet, Nedlands, WA 6009, Australia.;Univ Western Australia, Sch Med & Pharmacol, Crawley 6009, Australia.4 aut
700	1	a Ntzani, Evangelia E.u Univ Ioannina, Sch Med, Dept Hyg & Epidemiol, GR-45110 Ioannina, Greece.;Brown Univ, Sch Publ Hlth, Dept Hlth Serv Policy & Practice, Providence, RI 02903 USA.4 aut
700	1	a Brown, Matthew A.u Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.4 aut
700	1	a Stefansson, Kariu Univ Iceland, Fac Med, IS-101 Reykjavik, Iceland.;deCODE Genet, IS-101 Reykjavik, Iceland.4 aut
700	1	a Hinds, David A.u 23andMe, Res Dept, Mountain View, CA 94041 USA.4 aut
700	1	a Spector, Timu Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.4 aut
700	1	a Cupples, L. Adrienneu Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA.;Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA.4 aut
700	1	a Ohlsson, Claes,d 1965u Gothenburg University,Göteborgs universitet,Centre for Bone and Arthritis Research,Institutionen för medicin, avdelningen för invärtesmedicin och klinisk nutrition,Institute of Medicine, Department of Internal Medicine and Clinical Nutrition4 aut0 (Swepub:gu)xohlcl
700	1	a Greenwood, Celia M. T.u McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1B1, Canada.;McGill Univ, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Gerald Bronfman Ctr, Dept Oncol, Montreal, PQ H2W 1S6, Canada.4 aut
700	1	a Jackson, Rebecca D.u Ohio State Univ, Dept Med, Div Endocrinol Diabet & Metab, Columbus, OH 43210 USA.4 aut
700	1	a Rowe, David W.u Univ Connecticut, Ctr Hlth, Coll Dent Med, Dept Reconstruct Sci, Farmington, CT 06030 USA.4 aut
700	1	a Loomis, Cynthia A.u NYU, Sch Med, Ronald O Perelman Dept Dermatol, New York, NY 10016 USA.;NYU, Sch Med, Dept Cell Biol, New York, NY 10016 USA.4 aut
700	1	a Evans, David M.u Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.;Univ Bristol, MRC Integrat Epidemiol Unit, Bristol BS8 2BN, Avon, England.4 aut
700	1	a Ackert-Bicknell, Cheryl L.u Univ Rochester, Ctr Musculoskeletal Res, Rochester, NY 14642 USA.4 aut
700	1	a Joyner, Alexandra L.u Mem Sloan Kettering Canc Ctr, Dev Biol Program, New York, NY 10065 USA.4 aut
700	1	a Duncan, Emma L.u Univ Queensland, Diamantina Inst, Translat Res Inst, Princess Alexandra Hosp, Brisbane, Qld 4102, Australia.;Royal Brisbane & Womens Hosp, Dept Diabet & Endocrinol, Brisbane, Qld 4029, Australia.4 aut
700	1	a Kiel, Douglas P.u Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA.;Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02115 USA.4 aut
700	1	a Rivadeneira, Fernandou Erasmus MC, Dept Internal Med, NL-3015 GE Rotterdam, Netherlands.;Erasmus MC, Dept Epidemiol, NL-3015 GE Rotterdam, Netherlands.;NCHA, NGI, NL-2300 RC Leiden, Netherlands.4 aut
700	1	a Richards, J. Brentu McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.;Kings Coll London, Dept Twin Res & Genet Epidemiol, London SE1 7EH, England.4 aut
710	2	a McGill Univ, Dept Med, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Human Genet, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Epidemiol, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Dept Biostat, Montreal, PQ H3A 1A2, Canada.;McGill Univ, Jewish Gen Hosp, Lady Davis Inst Med Res, Dept Med, Montreal, PQ H3T 1E2, Canada.b Hebrew SeniorLife, Inst Aging Res, Boston, MA 02131 USA.;Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA.;Broad Inst MIT & Harvard, Boston, MA 02115 USA.4 org
773	0	t Natured : Springer Science and Business Media LLCg 526:7571, s. 112-+q 526:7571<112-+x 0028-0836x 1476-4687
856	4	u https://europepmc.org/articles/pmc4755714?pdf=render
856	4	u http://www.ncbi.nlm.nih.gov/pubmed/26367794?dopt=Abstracty FULLTEXT
856	4	u http://dx.doi.org/10.1038/nature14878y FULLTEXT
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-269270
856	4 8	u https://doi.org/10.1038/nature14878
856	4 8	u https://lup.lub.lu.se/record/8042189
856	4 8	u https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-112272
856	4 8	u https://gup.ub.gu.se/publication/226247

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By the author/editor: Zheng, Hou-Feng; Forgetta, Vincen ...; Hsu, Yi-Hsiang; Estrada, Karol; Rosello-Diez, Al ...; Leo, Paul J.; show more...; Dahia, Chitra L.; Park-Min, Kyung ...; Tobias, Jonathan ...; Kooperberg, Char ...; Kleinman, Aaron; Styrkarsdottir, ...; Liu, Ching-Ti; Uggla, Charlotta; Evans, Daniel S.; Nielson, Carrie ...; Walter, Klaudia; Pettersson-Kymme ...; McCarthy, Shane; Eriksson, Joel; Kwan, Tony; Jhamai, Mila; Trajanoska, Kate ...; Memari, Yasin; Min, Josine; Huang, Jie; Danecek, Petr; Wilmot, Beth; Li, Rui; Chou, Wen-Chi; Mokry, Lauren E.; Moayyeri, Alirez ...; Claussnitzer, Me ...; Cheng, Chia-Ho; Cheung, Warren; Medina-Gomez, Ca ...; Ge, Bing; Chen, Shu-Huang; Choi, Kwangbom; Oei, Ling; Fraser, James; Kraaij, Robert; Hibbs, Matthew A ...; Gregson, Celia L ...; Paquette, Denis; Hofman, Albert; Wibom, Carl; Tranah, Gregory ...; Marshall, Mhairi; Gardiner, Brooke ...; Cremin, Katie; Auer, Paul; Hsu, Li; Ring, Sue; Tung, Joyce Y.; Thorleifsson, Gu ...; Enneman, Anke W.; Mellström, Dan, ...; Garg, Gaurav; van der Velde, N ...; Melin, Beatrice; Kemp, John P.; Christiansen, Cl ...; Sayers, Adrian; Zhou, Yanhua; Calderari, Sophi ...; van Rooij, Jeroe ...; Carlson, Chris; Peters, Ulrike; Berlivet, Soizik; Dostie, Josee; Uitterlinden, An ...; Williams, Stephe ...; Farber, Charles; Grinberg, Daniel; LaCroix, Andrea ...; Haessler, Jeff; Chasman, Daniel ...; Giulianini, Fran ...; Rose, Lynda M.; Ridker, Paul M.; Eisman, John A.; Nguyen, Tuan V.; Center, Jacqueli ...; Nogues, Xavier; Garcia-Giralt, N ...; Launer, Lenore L ...; Gudnason, Vilmun ...; Mellstrom, Dan; Vandenput, Liesb ...; Amin, Najaf; van Duijn, Corne ...; Karlsson, Magnus; Ljunggren, Östen; Svensson, Olle; Hallmans, Göran; Rousseau, Franco ...; Giroux, Sylvie; Bussiere, Johann ...; Arp, Pascal P.; Koromani, Fjorda; Prince, Richard ...; Lewis, Joshua R.; Langdahl, Bente ...; Hermann, A. Pern ...; Jensen, Jens-Eri ...; Kaptoge, Stephen; Khaw, Kay-Tee; Reeve, Jonathan; Formosa, Melissa ...; Xuereb-Anastasi, ...; Åkesson, Kristin ...; McGuigan, Fiona; Olmos, Jose M.; Zarrabeitia, Mar ...; Riancho, Jose A.; Ralston, Stuart ...; Alonso, Nerea; Jiang, Xi; Goltzman, David; Pastinen, Tomi; Grundberg, Elin; Gauguier, Domini ...; Orwoll, Eric S.; Karasik, David; Davey-Smith, Geo ...; Smith, Albert V.; Siggeirsdottir, ...; Harris, Tamara B ...; Zillikens, M. Ca ...; van Meurs, Joyce ...; Thorsteinsdottir ...; Maurano, Matthew ...; Timpson, Nichola ...; Soranzo, Nicole; Durbin, Richard; Wilson, ScottG.; Ntzani, Evangeli ...; Brown, Matthew A ...; Stefansson, Kari; Hinds, David A.; Spector, Tim; Cupples, L. Adri ...; Ohlsson, Claes, ...; Greenwood, Celia ...; Jackson, Rebecca ...; Rowe, David W.; Loomis, Cynthia ...; Evans, David M.; Ackert-Bicknell, ...; Joyner, Alexandr ...; Duncan, Emma L.; Kiel, Douglas P.; Rivadeneira, Fer ...; Richards, J. Bre ...; show less...

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