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dc.contributor.author | Dornbos, Peter | |
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dc.contributor.author | Zhang, David | |
dc.contributor.author | Park, Joseph | |
dc.contributor.author | Aguilar-Salinas, Carlos A | |
dc.contributor.author | Antonacci-Fulton, Lucinda | |
dc.contributor.author | Ardissino, Diego | |
dc.contributor.author | Arnett, Donna K | |
dc.contributor.author | Aslibekyan, Stella | |
dc.contributor.author | Atzmon, Gil | |
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dc.contributor.author | Barajas-Olmos, Francisco | |
dc.contributor.author | Barzilai, Nir | |
dc.contributor.author | Becker, Lewis C | |
dc.contributor.author | Bielak, Lawrence F | |
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dc.contributor.author | Blangero, John | |
dc.contributor.author | Boerwinkle, Eric | |
dc.contributor.author | Bonnycastle, Lori L | |
dc.contributor.author | Bottinger, Erwin | |
dc.contributor.author | Bowden, Donald W | |
dc.contributor.author | Bown, Matthew J | |
dc.contributor.author | Brody, Jennifer A | |
dc.contributor.author | Broome, Jai G | |
dc.contributor.author | Burtt, Noël P | |
dc.contributor.author | Cade, Brian E | |
dc.contributor.author | Centeno-Cruz, Federico | |
dc.contributor.author | Chan, Edmund | |
dc.contributor.author | Chang, Yi-Cheng | |
dc.contributor.author | Chen, Yii-Der I | |
dc.contributor.author | Cheng, Ching-Yu | |
dc.contributor.author | Choi, Won Jung | |
dc.contributor.author | Chowdhury, Rajiv | |
dc.contributor.author | Contreras-Cubas, Cecilia | |
dc.contributor.author | Córdova, Emilio J | |
dc.contributor.author | Correa, Adolfo | |
dc.contributor.author | Cupples, L Adrienne | |
dc.contributor.author | Curran, Joanne E | |
dc.contributor.author | Danesh, John | |
dc.contributor.author | de Vries, Paul S | |
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dc.contributor.author | Doddapaneni, Harsha | |
dc.contributor.author | Duggirala, Ravindranath | |
dc.contributor.author | Dutcher, Susan K | |
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dc.contributor.author | García-Ortiz, Humberto | |
dc.contributor.author | Germer, Soren | |
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dc.contributor.author | Gieger, Christian | |
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dc.contributor.author | Gonzalez-Villalpando, Maria Elena | |
dc.contributor.author | Graff, Mariaelisa | |
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dc.contributor.author | Han, Sohee | |
dc.contributor.author | Hanis, Craig L | |
dc.contributor.author | Hansen, Torben | |
dc.contributor.author | He, Jiang | |
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dc.contributor.author | Islas-Andrade, Sergio | |
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dc.contributor.author | Kelly, Tanika | |
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dc.contributor.author | Kim, Bong-Jo | |
dc.contributor.author | Kim, Ryan W | |
dc.contributor.author | Kim, Young Jin | |
dc.contributor.author | Koistinen, Heikki A | |
dc.contributor.author | Kooperberg, Charles | |
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dc.contributor.author | Schunkert, Heribert | |
dc.contributor.author | Schurmann, Claudia | |
dc.contributor.author | Seo, Daekwan | |
dc.contributor.author | Seo, Jeong-Sun | |
dc.contributor.author | Sim, Xueling | |
dc.contributor.author | Sladek, Rob | |
dc.contributor.author | Small, Kerrin S | |
dc.contributor.author | So, Wing Yee | |
dc.contributor.author | Stilp, Adrienne M | |
dc.contributor.author | Tai, E Shyong | |
dc.contributor.author | Tam, Claudia H T | |
dc.contributor.author | Taylor, Kent D | |
dc.contributor.author | Teo, Yik Ying | |
dc.contributor.author | Thameem, Farook | |
dc.contributor.author | Tomlinson, Brian | |
dc.contributor.author | Tsai, Michael Y | |
dc.contributor.author | Tuomi, Tiinamaija | |
dc.contributor.author | Tuomilehto, Jaakko | |
dc.contributor.author | Tusié-Luna, Teresa | |
dc.contributor.author | Udler, Miriam S | |
dc.contributor.author | van Dam, Rob M | |
dc.contributor.author | Vasan, Ramachandran S | |
dc.contributor.author | Viaud Martinez, Karine A | |
dc.contributor.author | Wang, Fei Fei | |
dc.contributor.author | Wang, Xuzhi | |
dc.contributor.author | Watkins, Hugh | |
dc.contributor.author | Weeks, Daniel E | |
dc.contributor.author | Wilson, James G | |
dc.contributor.author | Witte, Daniel R | |
dc.contributor.author | Wong, Tien-Yin | |
dc.contributor.author | Yanek, Lisa R | |
dc.contributor.author | Kathiresan, Sekar | |
dc.contributor.author | Rader, Daniel J | |
dc.contributor.author | Rotter, Jerome I | |
dc.contributor.author | Boehnke, Michael | |
dc.contributor.author | McCarthy, Mark I | |
dc.contributor.author | Willer, Cristen J | |
dc.contributor.author | Natarajan, Pradeep | |
dc.contributor.author | Flannick, Jason A | |
dc.contributor.author | Khera, Amit V | |
dc.contributor.author | Peloso, Gina M | |
dc.date.accessioned | 2023-03-14T15:53:07Z | |
dc.date.available | 2023-03-14T15:53:07Z | |
dc.date.issued | 2022-01-06 | |
dc.identifier.citation | Am J Hum Genet. 2022 Jan 6;109(1):81-96 | es_ES |
dc.identifier.uri | http://hdl.handle.net/20.500.12105/15626 | |
dc.description.abstract | Large-scale gene sequencing studies for complex traits have the potential to identify causal genes with therapeutic implications. We performed gene-based association testing of blood lipid levels with rare (minor allele frequency < 1%) predicted damaging coding variation by using sequence data from >170,000 individuals from multiple ancestries: 97,493 European, 30,025 South Asian, 16,507 African, 16,440 Hispanic/Latino, 10,420 East Asian, and 1,182 Samoan. We identified 35 genes associated with circulating lipid levels; some of these genes have not been previously associated with lipid levels when using rare coding variation from population-based samples. We prioritize 32 genes in array-based genome-wide association study (GWAS) loci based on aggregations of rare coding variants; three (EVI5, SH2B3, and PLIN1) had no prior association of rare coding variants with lipid levels. Most of our associated genes showed evidence of association among multiple ancestries. Finally, we observed an enrichment of gene-based associations for low-density lipoprotein cholesterol drug target genes and for genes closest to GWAS index single-nucleotide polymorphisms (SNPs). Our results demonstrate that gene-based associations can be beneficial for drug target development and provide evidence that the gene closest to the array-based GWAS index SNP is often the functional gene for blood lipid levels. | es_ES |
dc.description.sponsorship | This work was supported by a grant from the Swedish Research
Council (2016-06830) and grants from the National Heart, Lung,
and Blood Institute (NHLBI): R01HL142711 and R01HL127564.
Please refer to the supplemental information for the full
acknowledgements. | es_ES |
dc.language.iso | eng | es_ES |
dc.publisher | American Society of Human Genetics | es_ES |
dc.type.hasVersion | VoR | es_ES |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | * |
dc.subject.mesh | Exome | es_ES |
dc.subject.mesh | Genetic Variation | es_ES |
dc.subject.mesh | Genome-Wide Association Study | es_ES |
dc.subject.mesh | Open Reading Frames | es_ES |
dc.subject.mesh | Alleles | es_ES |
dc.subject.mesh | Blood Glucose | es_ES |
dc.subject.mesh | Case-Control Studies | es_ES |
dc.subject.mesh | Computational Biology | es_ES |
dc.subject.mesh | Databases, Genetic | es_ES |
dc.subject.mesh | Diabetes Mellitus, Type 2 | es_ES |
dc.subject.mesh | Genetic Predisposition to Disease | es_ES |
dc.subject.mesh | Genetics, Population | es_ES |
dc.subject.mesh | Humans | es_ES |
dc.subject.mesh | Lipid Metabolism | es_ES |
dc.subject.mesh | Lipids | es_ES |
dc.subject.mesh | Liver | es_ES |
dc.subject.mesh | Molecular Sequence Annotation | es_ES |
dc.subject.mesh | Multifactorial Inheritance | es_ES |
dc.subject.mesh | Phenotype | es_ES |
dc.subject.mesh | Polymorphism, Single Nucleotide | es_ES |
dc.title | Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes. | es_ES |
dc.type | journal article | es_ES |
dc.rights.license | Atribución 4.0 Internacional | * |
dc.identifier.pubmedID | 34932938 | es_ES |
dc.format.volume | 109 | es_ES |
dc.format.number | 1 | es_ES |
dc.format.page | 81 | es_ES |
dc.identifier.doi | 10.1016/j.ajhg.2021.11.021 | es_ES |
dc.contributor.funder | NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos) | es_ES |
dc.description.peerreviewed | Sí | es_ES |
dc.identifier.e-issn | 1537-6605 | es_ES |
dc.relation.publisherversion | https://doi.org/10.1016/j.ajhg.2021.11.021 | es_ES |
dc.identifier.journal | American journal of human genetics | es_ES |
dc.repisalud.orgCNIC | CNIC::Grupos de investigación::Imagen Cardiovascular y Estudios Poblacionales | es_ES |
dc.repisalud.institucion | CNIC | es_ES |
dc.rights.accessRights | open access | es_ES |