dc.contributor.author | Surakka, Ida | |
dc.contributor.author | Fritsche, Lars | |
dc.contributor.author | Zhou, Wei | |
dc.contributor.author | Backman, Joshua | |
dc.contributor.author | Kosmicki, Jack A. | |
dc.contributor.author | Lu, Haocheng | |
dc.contributor.author | Brumpton, Ben Michael | |
dc.contributor.author | Nielsen, Jonas B. | |
dc.contributor.author | Gabrielsen, Maiken Elvestad | |
dc.contributor.author | Skogholt, Anne Heidi | |
dc.contributor.author | Wolford, Brooke N. | |
dc.contributor.author | Graham, Sarah E. | |
dc.contributor.author | Chen, Y. Eugene | |
dc.contributor.author | Lee, Seunggeun | |
dc.contributor.author | Kang, Hyun Min | |
dc.contributor.author | Langhammer, Arnulf | |
dc.contributor.author | Forsmo, Siri | |
dc.contributor.author | Åsvold, Bjørn Olav | |
dc.contributor.author | Styrkarsdottir, Unnur | |
dc.contributor.author | Holm, Hilma | |
dc.contributor.author | Gudbjartsson, Daniel F. | |
dc.contributor.author | Stefansson, Kari | |
dc.contributor.author | Baras, Aris | |
dc.contributor.author | Bai, Xiaodong | |
dc.contributor.author | Balasubramanian, Suganthi | |
dc.contributor.author | Barnard, Leland | |
dc.contributor.author | Blumenfeld, Andrew | |
dc.contributor.author | Cantor, Michael | |
dc.contributor.author | Coppola, Giovanni | |
dc.contributor.author | Economides, Aris | |
dc.contributor.author | Eom, Gisu | |
dc.contributor.author | Habegger, Lukas | |
dc.contributor.author | Hahn, Young | |
dc.contributor.author | Hawes, Alicia | |
dc.contributor.author | Jones, Marcus B. | |
dc.contributor.author | Khalid, Shareef | |
dc.contributor.author | Lotta, Luca A. | |
dc.contributor.author | Maxwell, Evan K. | |
dc.contributor.author | Mitnaul, Lyndon J. | |
dc.contributor.author | Overton, John D. | |
dc.contributor.author | Reid, Jeffrey G. | |
dc.contributor.author | Ferreira, Manuel Allen Revez | |
dc.contributor.author | Salerno, William | |
dc.contributor.author | Sharma, Deepika | |
dc.contributor.author | Shuldiner, Alan R. | |
dc.contributor.author | Staples, Jeffrey C. | |
dc.contributor.author | Yadav, Ashish | |
dc.contributor.author | Abecasis, Goncalo R. | |
dc.contributor.author | Hveem, Kristian | |
dc.contributor.author | Willer, Cristen J. | |
dc.date.accessioned | 2021-04-28T07:06:21Z | |
dc.date.available | 2021-04-28T07:06:21Z | |
dc.date.created | 2020-11-13T13:38:36Z | |
dc.date.issued | 2020 | |
dc.identifier.citation | Nature Communications. 2020, 11:4093 1-8. | en_US |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://hdl.handle.net/11250/2740019 | |
dc.description.abstract | A major challenge in genetic association studies is that most associated variants fall in the non-coding part of the human genome. We searched for variants associated with bone mineral density (BMD) after enriching the discovery cohort for loss-of-function (LoF) mutations by sequencing a subset of the Nord-Trøndelag Health Study, followed by imputation in the remaining sample (N = 19,705), and identified ten known BMD loci. However, one previously unreported variant, LoF mutation in MEPE, p.(Lys70IlefsTer26, minor allele frequency [MAF] = 0.8%), was associated with decreased ultradistal forearm BMD (P-value = 2.1 × 10−18), and increased osteoporosis (P-value = 4.2 × 10−5) and fracture risk (P-value = 1.6 × 10−5). The MEPE LoF association with BMD and fractures was further evaluated in 279,435 UK (MAF = 0.05%, heel bone estimated BMD P-value = 1.2 × 10−16, any fracture P-value = 0.05) and 375,984 Icelandic samples (MAF = 0.03%, arm BMD P-value = 0.12, forearm fracture P-value = 0.005). Screening for the MEPE LoF mutations before adulthood could potentially prevent osteoporosis and fractures due to the lifelong effect on BMD observed in the study. A key implication for precision medicine is that high-impact functional variants missing from the publicly available cosmopolitan panels could be clinically more relevant than polygenic risk scores. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Nature Research | en_US |
dc.rights | Navngivelse 4.0 Internasjonal | * |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/deed.no | * |
dc.title | MEPE loss-of-function variant associates with decreased bone mineral density and increased fracture risk | en_US |
dc.type | Peer reviewed | en_US |
dc.type | Journal article | en_US |
dc.description.version | publishedVersion | en_US |
dc.source.pagenumber | 1-8 | en_US |
dc.source.volume | 11:4093 | en_US |
dc.source.journal | Nature Communications | en_US |
dc.identifier.doi | 10.1038/s41467-020-17315-0 | |
dc.identifier.cristin | 1847753 | |
dc.relation.project | Stiftelsen Kristian Gerhard Jebsen: SKGJ-MED015 | en_US |
cristin.ispublished | true | |
cristin.fulltext | original | |
cristin.qualitycode | 2 | |