2026-04-29T12:24:23Zhttps://repisalud.isciii.es/rest/oai/request
oai:repisalud.isciii.es:20.500.12105/156262025-05-08T14:59:34Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605
Repisalud author Hindy, George author Dornbos, Peter author Chaffin, Mark D author Liu, Dajiang J author Wang, Minxian author Selvaraj, Margaret Sunitha author Zhang, David author Park, Joseph author Aguilar-Salinas, Carlos A author Antonacci-Fulton, Lucinda author Ardissino, Diego author Arnett, Donna K author Aslibekyan, Stella author Atzmon, Gil author Ballantyne, Christie M author Barajas-Olmos, Francisco author Barzilai, Nir author Becker, Lewis C author Bielak, Lawrence F author Bis, Joshua C author Blangero, John author Boerwinkle, Eric author Bonnycastle, Lori L author Bottinger, Erwin author Bowden, Donald W author Bown, Matthew J author Brody, Jennifer A author Broome, Jai G author Burtt, Noël P author Cade, Brian E author Centeno-Cruz, Federico author Chan, Edmund author Chang, Yi-Cheng author Chen, Yii-Der I author Cheng, Ching-Yu author Choi, Won Jung author Chowdhury, Rajiv author Contreras-Cubas, Cecilia author Córdova, Emilio J author Correa, Adolfo author Cupples, L Adrienne author Curran, Joanne E author Danesh, John author de Vries, Paul S author DeFronzo, Ralph A author Doddapaneni, Harsha author Duggirala, Ravindranath author Dutcher, Susan K author Ellinor, Patrick T author Emery, Leslie S author Florez, Jose C author Fornage, Myriam author Freedman, Barry I author Fuster, Valentin author Garay-Sevilla, Ma Eugenia author García-Ortiz, Humberto author Germer, Soren author Gibbs, Richard A author Gieger, Christian author Glaser, Benjamin author Gonzalez, Clicerio author Gonzalez-Villalpando, Maria Elena author Graff, Mariaelisa author Graham, Sarah E author Grarup, Niels author Groop, Leif C author Guo, Xiuqing author Gupta, Namrata author Han, Sohee author Hanis, Craig L author Hansen, Torben author He, Jiang author Heard-Costa, Nancy L author Hung, Yi-Jen author Hwang, Mi Yeong author Irvin, Marguerite R author Islas-Andrade, Sergio author Jarvik, Gail P author Kang, Hyun Min author Kardia, Sharon L R author Kelly, Tanika author Kenny, Eimear E author Khan, Alyna T author Kim, Bong-Jo author Kim, Ryan W author Kim, Young Jin author Koistinen, Heikki A author Kooperberg, Charles author Kuusisto, Johanna author Kwak, Soo Heon author Laakso, Markku author Lange, Leslie A author Lee, Jiwon author Lee, Juyoung author Lee, Seonwook author Lehman, Donna M author Lemaitre, Rozenn N author Linneberg, Allan author Liu, Jianjun author Loos, Ruth J F author Lubitz, Steven A author Lyssenko, Valeriya author Ma, Ronald C W author Martin, Lisa Warsinger author Martínez-Hernández, Angélica author Mathias, Rasika A author McGarvey, Stephen T author McPherson, Ruth author Meigs, James B author Meitinger, Thomas author Melander, Olle author Mendoza-Caamal, Elvia author Metcalf, Ginger A author Mi, Xuenan author Mohlke, Karen L author Montasser, May E author Moon, Jee-Young author Moreno-Macías, Hortensia author Morrison, Alanna C author Muzny, Donna M author Nelson, Sarah C author Nilsson, Peter M author O'Connell, Jeffrey R author Orho-Melander, Marju author Orozco, Lorena author Palmer, Colin N A author Palmer, Nicholette D author Park, Cheol Joo author Park, Kyong Soo author Pedersen, Oluf author Peralta, Juan M author Peyser, Patricia A author Post, Wendy S author Preuss, Michael author Psaty, Bruce M author Qi, Qibin author Rao, D C author Redline, Susan author Reiner, Alexander P author Revilla-Monsalve, Cristina author Rich, Stephen S author Samani, Nilesh author Schunkert, Heribert author Schurmann, Claudia author Seo, Daekwan author Seo, Jeong-Sun author Sim, Xueling author Sladek, Rob author Small, Kerrin S author So, Wing Yee author Stilp, Adrienne M author Tai, E-Shyong author Tam, Claudia H T author Taylor, Kent D author Teo, Yik Ying author Thameem, Farook author Tomlinson, Brian author Tsai, Michael Y author Tuomi, Tiinamaija author Tuomilehto, Jaakko author Tusié-Luna, Teresa author Udler, Miriam S author van Dam, Rob M author Vasan, Ramachandran S author Viaud Martinez, Karine A author Wang, Fei Fei author Wang, Xuzhi author Watkins, Hugh author Weeks, Daniel E author Wilson, James G author Witte, Daniel R author Wong, Tien-Yin author Yanek, Lisa R author Kathiresan, Sekar author Rader, Daniel J author Rotter, Jerome I author Boehnke, Michael author McCarthy, Mark I author Willer, Cristen J author Natarajan, Pradeep author Flannick, Jason A author Khera, Amit V author Peloso, Gina M funder NIH - National Heart, Lung, and Blood Institute (NHLBI) (Estados Unidos) 2023-03-14T15:53:07Z 2023-03-14T15:53:07Z 2022-01-06 Am J Hum Genet. 2022 Jan 6;109(1):81-96 10.1016/j.ajhg.2021.11.021 1537-6605 American journal of human genetics 34932938 http://hdl.handle.net/20.500.12105/15626 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. eng Rare coding variants in 35 genes associate with circulating lipid levels-A multi-ancestry analysis of 170,000 exomes. journal article 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 URL https://repisalud.isciii.es/bitstreams/7c65adc8-6f34-4970-b7d5-1c3f184361e8/download File MD5 59ce334019a2c2c79e5f2b6368081d7b 1326075 application/pdf Rare coding variants in Am J Hum Genet 2022.pdf URL https://repisalud.isciii.es/bitstreams/956af468-18f6-4142-b700-662c84c9ced1/download File MD5 e375671eb377bd85064d8292c84e125d 94789 text/plain Rare coding variants in Am J Hum Genet 2022.pdf.txt