An atlas of genetic influences on osteoporosis in humans and mice.

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Fältnamn	Indikatorer	Metadata
000		04980naa a2200985 4500
001		oai:gup.ub.gu.se/276254
003		SwePub
008		240528s2019 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://gup.ub.gu.se/publication/2762542 URI
024	7	a https://doi.org/10.1038/s41588-018-0302-x2 DOI
040		a (SwePub)gu
041		a eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Morris, John A4 aut
245	1 0	a An atlas of genetic influences on osteoporosis in humans and mice.
264		c 2018-12-31
264	1	b Springer Science and Business Media LLC,c 2019
520		a Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR)=58, P=1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P<0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.
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 Kemp, John P4 aut
700	1	a Youlten, Scott E4 aut
700	1	a Laurent, Laetitia4 aut
700	1	a Logan, John G4 aut
700	1	a Chai, Ryan C4 aut
700	1	a Vulpescu, Nicholas A4 aut
700	1	a Forgetta, Vincenzo4 aut
700	1	a Kleinman, Aaron4 aut
700	1	a Mohanty, Sindhu T4 aut
700	1	a Sergio, C Marcelo4 aut
700	1	a Quinn, Julian4 aut
700	1	a Nguyen-Yamamoto, Loan4 aut
700	1	a Luco, Aimee-Lee4 aut
700	1	a Vijay, Jinchu4 aut
700	1	a Simon, Marie-Michelle4 aut
700	1	a Pramatarova, Albena4 aut
700	1	a Medina-Gomez, Carolina4 aut
700	1	a Trajanoska, Katerina4 aut
700	1	a Ghirardello, Elena J4 aut
700	1	a Butterfield, Natalie C4 aut
700	1	a Curry, Katharine F4 aut
700	1	a Leitch, Victoria D4 aut
700	1	a Sparkes, Penny C4 aut
700	1	a Adoum, Anne-Tounsia4 aut
700	1	a Mannan, Naila S4 aut
700	1	a Komla-Ebri, Davide S K4 aut
700	1	a Pollard, Andrea S4 aut
700	1	a Dewhurst, Hannah F4 aut
700	1	a Hassall, Thomas A D4 aut
700	1	a Beltejar, Michael-John G4 aut
700	1	a Adams, Douglas J4 aut
700	1	a Vaillancourt, Suzanne M4 aut
700	1	a Kaptoge, Stephen4 aut
700	1	a Baldock, Paul4 aut
700	1	a Cooper, Cyrus4 aut
700	1	a Reeve, Jonathan4 aut
700	1	a Ntzani, Evangelia E4 aut
700	1	a Evangelou, Evangelos4 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 Karasik, David4 aut
700	1	a Rivadeneira, Fernando4 aut
700	1	a Kiel, Douglas P4 aut
700	1	a Tobias, Jonathan H4 aut
700	1	a Gregson, Celia L4 aut
700	1	a Harvey, Nicholas C4 aut
700	1	a Grundberg, Elin4 aut
700	1	a Goltzman, David4 aut
700	1	a Adams, David J4 aut
700	1	a Lelliott, Christopher J4 aut
700	1	a Hinds, David A4 aut
700	1	a Ackert-Bicknell, Cheryl L4 aut
700	1	a Hsu, Yi-Hsiang4 aut
700	1	a Maurano, Matthew T4 aut
700	1	a Croucher, Peter I4 aut
700	1	a Williams, Graham R4 aut
700	1	a Bassett, J H Duncan4 aut
700	1	a Evans, David M4 aut
700	1	a Richards, J Brent4 aut
710	2	a Göteborgs universitetb Centre for Bone and Arthritis Research4 org
773	0	t Nature geneticsd : Springer Science and Business Media LLCg 51, s. 258-266q 51<258-266x 1546-1718x 1061-4036
856	4	u https://europepmc.org/articles/pmc6358485?pdf=render
856	4 8	u https://gup.ub.gu.se/publication/276254
856	4 8	u https://doi.org/10.1038/s41588-018-0302-x

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Av författaren/redakt...: Morris, John A; Kemp, John P; Youlten, Scott E; Laurent, Laetiti ...; Logan, John G; Chai, Ryan C; visa fler...; Vulpescu, Nichol ...; Forgetta, Vincen ...; Kleinman, Aaron; Mohanty, Sindhu ...; Sergio, C Marcel ...; Quinn, Julian; Nguyen-Yamamoto, ...; Luco, Aimee-Lee; Vijay, Jinchu; Simon, Marie-Mic ...; Pramatarova, Alb ...; Medina-Gomez, Ca ...; Trajanoska, Kate ...; Ghirardello, Ele ...; Butterfield, Nat ...; Curry, Katharine ...; Leitch, Victoria ...; Sparkes, Penny C; Adoum, Anne-Toun ...; Mannan, Naila S; Komla-Ebri, Davi ...; Pollard, Andrea ...; Dewhurst, Hannah ...; Hassall, Thomas ...; Beltejar, Michae ...; Adams, Douglas J; Vaillancourt, Su ...; Kaptoge, Stephen; Baldock, Paul; Cooper, Cyrus; Reeve, Jonathan; Ntzani, Evangeli ...; Evangelou, Evang ...; Ohlsson, Claes, ...; Karasik, David; Rivadeneira, Fer ...; Kiel, Douglas P; Tobias, Jonathan ...; Gregson, Celia L; Harvey, Nicholas ...; Grundberg, Elin; Goltzman, David; Adams, David J; Lelliott, Christ ...; Hinds, David A; Ackert-Bicknell, ...; Hsu, Yi-Hsiang; Maurano, Matthew ...; Croucher, Peter ...; Williams, Graham ...; Bassett, J H Dun ...; Evans, David M; Richards, J Bren ...; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Endokrinologi oc ...

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Av lärosätet: Göteborgs universitet

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