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Please use this identifier to cite or link to this item:
http://ir.nhri.org.tw/handle/3990099045/14601
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| Title: | Whole genome sequence analysis of blood lipid levels in >66,000 individuals |
| Authors: | Selvaraj, MS;Li, X;Li, Z;Pampana, A;Zhang, DY;Park, J;Aslibekyan, S;Bis, JC;Brody, JA;Cade, BE;Chuang, LM;Chung, RH;Curran, JE;de Las Fuentes, L;de Vries, PS;Duggirala, R;Freedman, BI;Graff, M;Guo, X;Heard-Costa, N;Hidalgo, B;Hwu, CM;Irvin, MR;Kelly, TN;Kral, BG;Lange, L;Li, X;Lisa, M;Lubitz, SA;Manichaikul, AW;Michael, P;Montasser, ME;Morrison, AC;Naseri, T;O'Connell, JR;Palmer, ND;Peyser, PA;Reupena, MS;Smith, JA;Sun, X;Taylor, KD;Tracy, RP;Tsai, MY;Wang, Z;Wang, Y;Bao, W;Wilkins, JT;Yanek, LR;Zhao, W;Arnett, DK;Blangero, J;Boerwinkle, E;Bowden, DW;Chen, YI;Correa, A;Cupples, LA;Dutcher, SK;Ellinor, PT;Fornage, M;Gabriel, S;Germer, S;Gibbs, R;He, J;Kaplan, RC;Kardia, SLR;Kim, R;Kooperberg, C;Loos, RJF;Viaud-Martinez, KA;Mathias, RA;McGarvey, ST;Mitchell, BD;Nickerson, D;North, KE;Psaty, BM;Redline, S;Reiner, AP;Vasan, RS;Rich, SS;Willer, C;Rotter, JI;Rader, DJ;Lin, X;Peloso, GM;Natarajan, P |
| Contributors: | Institute of Population Health Sciences |
| Abstract: | Blood lipids are heritable modifiable causal factors for coronary artery disease. Despite well-described monogenic and polygenic bases of dyslipidemia, limitations remain in discovery of lipid-associated alleles using whole genome sequencing (WGS), partly due to limited sample sizes, ancestral diversity, and interpretation of clinical significance. Among 66,329 ancestrally diverse (56% non-European) participants, we associate 428M variants from deep-coverage WGS with lipid levels; ~400M variants were not assessed in prior lipids genetic analyses. We find multiple lipid-related genes strongly associated with blood lipids through analysis of common and rare coding variants. We discover several associated rare non-coding variants, largely at Mendelian lipid genes. Notably, we observe rare LDLR intronic variants associated with markedly increased LDL-C, similar to rare LDLR exonic variants. In conclusion, we conducted a systematic whole genome scan for blood lipids expanding the alleles linked to lipids for multiple ancestries and characterize a clinically-relevant rare non-coding variant model for lipids. |
| Date: | 2022-10-11 |
| Relation: | Nature Communications. 2022 Oct 11;13:Article number 5995. |
| Link to: | http://dx.doi.org/10.1038/s41467-022-33510-7 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2041-1723&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000866124200006 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85139608936 |
| Appears in Collections: | [鍾仁華] 期刊論文
[熊昭] 期刊論文
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| PUB36220816.pdf | | 2967Kb | Adobe PDF | 189 | View/Open |
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