.2023 Oct 5;110(10):1704-1717.

doi: 10.1016/j.ajhg.2023.09.003.

Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

Yuxuan Wang¹, Margaret Sunitha Selvaraj², Xihao Li³, Zilin Li⁴, Jacob A Holdcraft¹, Donna K Arnett⁵, Joshua C Bis⁶, John Blangero⁷, Eric Boerwinkle⁸, Donald W Bowden⁹, Brian E Cade¹⁰, Jenna C Carlson¹¹, April P Carson¹², Yii-Der Ida Chen¹³, Joanne E Curran⁷, Paul S de Vries⁸, Susan K Dutcher¹⁴, Patrick T Ellinor¹⁵, James S Floyd¹⁶, Myriam Fornage¹⁷, Barry I Freedman¹⁸, Stacey Gabriel¹⁹, Soren Germer²⁰, Richard A Gibbs²¹, Xiuqing Guo¹³, Jiang He²², Nancy Heard-Costa²³, Bertha Hildalgo²⁴, Lifang Hou²⁵, Marguerite R Irvin²⁴, Roby Joehanes²⁶, Robert C Kaplan²⁷, Sharon Lr Kardia²⁸, Tanika N Kelly²⁹, Ryan Kim³⁰, Charles Kooperberg³¹, Brian G Kral³², Daniel Levy³³, Changwei Li³⁴, Chunyu Liu³⁵, Don Lloyd-Jone²⁵, Ruth Jf Loos³⁶, Michael C Mahaney⁷, Lisa W Martin³⁷, Rasika A Mathias³², Ryan L Minster³⁸, Braxton D Mitchell³⁹, May E Montasser³⁹, Alanna C Morrison⁸, Joanne M Murabito⁴⁰, Take Naseri⁴¹, Jeffrey R O'Connell³⁹, Nicholette D Palmer⁹, Michael H Preuss⁴², Bruce M Psaty⁴³, Laura M Raffield⁴⁴, Dabeeru C Rao⁴⁵, Susan Redline⁴⁶, Alexander P Reiner⁴⁷, Stephen S Rich⁴⁸, Muagututi'a Sefuiva Ruepena⁴⁹, Wayne H-H Sheu⁵⁰, Jennifer A Smith²⁸, Albert Smith⁵¹, Hemant K Tiwari⁵², Michael Y Tsai⁵³, Karine A Viaud-Martinez⁵⁴, Zhe Wang⁴², Lisa R Yanek³², Wei Zhao²⁸; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Jerome I Rotter¹³, Xihong Lin⁵⁵, Pradeep Natarajan², Gina M Peloso⁵⁶

Affiliations

¹ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
² Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
³ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ School of Mathematics and Statistics, Northeast Normal University, Changchun, Jilin, China; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵ Provost Office, University of South Carolina, Columbia, SC, USA; Department of Epidemiology and Biostatistics, University of South Carolina Arnold School of Public Health, Columbia, SC, USA.
⁶ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
⁷ Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
⁸ Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁹ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹⁰ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biostatistics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
¹² Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
¹³ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹⁴ The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
¹⁵ Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁶ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁷ Center for Human Genetics, University of Texas Health at Houston, Houston, TX, USA.
¹⁸ Department of Internal Medicine, Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹⁹ Broad Institute of Harvard and MIT, Cambridge, MA, USA.
²⁰ New York Genome Center, New York, NY, USA.
²¹ Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA.
²² Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Tulane University Translational Science Institute, New Orleans, LA, USA.
²³ Framingham Heart Study, Framingham, MA, USA; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
²⁴ Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA.
²⁵ Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
²⁶ Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
²⁷ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
²⁸ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
²⁹ Department of Medicine, Division of Nephrology, University of Illinois Chicago, Chicago, IL, USA.
³⁰ Psomagen, Inc. (formerly Macrogen USA), Rockville, MD, USA.
³¹ Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³² GeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³³ Framingham Heart Study, Framingham, MA, USA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
³⁴ Tulane University Translational Science Institute, New Orleans, LA, USA; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
³⁵ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; Framingham Heart Study, Framingham, MA, USA.
³⁶ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; NNF Center for Basic Metabolic Research, University of Copenhagen, Cophenhagen, Denmark.
³⁷ George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
³⁸ Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
³⁹ Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴⁰ Framingham Heart Study, Framingham, MA, USA; Department of Medicine, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
⁴¹ Naseri & Associates Public Health Consultancy Firm and Family Health Clinic, Apia, Samoa; International Health Institute, School of Public Health, Brown University, Providence, RI, USA.
⁴² The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴³ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.
⁴⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁵ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
⁴⁶ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁴⁸ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁴⁹ Lutia i Puava ae Mapu i Fagalele, Apia, Samoa.
⁵⁰ Institute of Molecular and Genomic Medicine, National Health Research Institute (NHRI), Miaoli County, Taiwan.
⁵¹ Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
⁵² Department of Biostatistics, University of Alabama, Birmingham, AL, USA.
⁵³ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
⁵⁴ Illumina Laboratory Services, Illumina Inc., San Diego, CA, USA.
⁵⁵ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Statistics, Harvard University, Cambridge, MA, USA.
⁵⁶ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. Electronic address: gpeloso@bu.edu.

PMID:37802043
PMCID: PMC10577076
DOI: 10.1016/j.ajhg.2023.09.003

Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

Yuxuan Wang et al. Am J Hum Genet.2023.

.2023 Oct 5;110(10):1704-1717.

doi: 10.1016/j.ajhg.2023.09.003.

Authors

Affiliations

¹ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
² Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, USA; Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Medicine, Harvard Medical School, Boston, MA, USA.
³ Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴ School of Mathematics and Statistics, Northeast Normal University, Changchun, Jilin, China; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
⁵ Provost Office, University of South Carolina, Columbia, SC, USA; Department of Epidemiology and Biostatistics, University of South Carolina Arnold School of Public Health, Columbia, SC, USA.
⁶ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
⁷ Department of Human Genetics and South Texas Diabetes and Obesity Institute, University of Texas Rio Grande Valley School of Medicine, Brownsville, TX, USA.
⁸ Human Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, USA.
⁹ Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹⁰ Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Division of Sleep Medicine, Harvard Medical School, Boston, MA, USA.
¹¹ Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biostatistics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
¹² Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
¹³ The Institute for Translational Genomics and Population Sciences, Department of Pediatrics, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
¹⁴ The McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA.
¹⁵ Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA; Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁶ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA.
¹⁷ Center for Human Genetics, University of Texas Health at Houston, Houston, TX, USA.
¹⁸ Department of Internal Medicine, Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
¹⁹ Broad Institute of Harvard and MIT, Cambridge, MA, USA.
²⁰ New York Genome Center, New York, NY, USA.
²¹ Baylor College of Medicine Human Genome Sequencing Center, Houston, TX, USA.
²² Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA; Tulane University Translational Science Institute, New Orleans, LA, USA.
²³ Framingham Heart Study, Framingham, MA, USA; Department of Neurology, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.
²⁴ Department of Epidemiology, University of Alabama at Birmingham School of Public Health, Birmingham, AL, USA.
²⁵ Department of Preventive Medicine, Northwestern University, Chicago, IL, USA.
²⁶ Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
²⁷ Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA; Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
²⁸ Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
²⁹ Department of Medicine, Division of Nephrology, University of Illinois Chicago, Chicago, IL, USA.
³⁰ Psomagen, Inc. (formerly Macrogen USA), Rockville, MD, USA.
³¹ Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.
³² GeneSTAR Research Program, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
³³ Framingham Heart Study, Framingham, MA, USA; Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA.
³⁴ Tulane University Translational Science Institute, New Orleans, LA, USA; Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
³⁵ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA; Framingham Heart Study, Framingham, MA, USA.
³⁶ The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; NNF Center for Basic Metabolic Research, University of Copenhagen, Cophenhagen, Denmark.
³⁷ George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
³⁸ Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
³⁹ Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
⁴⁰ Framingham Heart Study, Framingham, MA, USA; Department of Medicine, Boston Medical Center, Boston University Chobanian and Avedisian School of Medicine, Boston, MA, USA.
⁴¹ Naseri & Associates Public Health Consultancy Firm and Family Health Clinic, Apia, Samoa; International Health Institute, School of Public Health, Brown University, Providence, RI, USA.
⁴² The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
⁴³ Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, Seattle, WA, USA; Department of Health Systems and Population Health, University of Washington, Seattle, WA, USA.
⁴⁴ Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
⁴⁵ Division of Biostatistics, Washington University School of Medicine, St. Louis, MO, USA.
⁴⁶ Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴⁷ Department of Epidemiology, University of Washington, Seattle, WA, USA.
⁴⁸ Center for Public Health Genomics, University of Virginia, Charlottesville, VA, USA.
⁴⁹ Lutia i Puava ae Mapu i Fagalele, Apia, Samoa.
⁵⁰ Institute of Molecular and Genomic Medicine, National Health Research Institute (NHRI), Miaoli County, Taiwan.
⁵¹ Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
⁵² Department of Biostatistics, University of Alabama, Birmingham, AL, USA.
⁵³ Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
⁵⁴ Illumina Laboratory Services, Illumina Inc., San Diego, CA, USA.
⁵⁵ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, USA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Statistics, Harvard University, Cambridge, MA, USA.
⁵⁶ Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA. Electronic address: gpeloso@bu.edu.

PMID:37802043
PMCID: PMC10577076
DOI: 10.1016/j.ajhg.2023.09.003

Abstract

Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions in lipid metabolism. Large-scale whole-genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess more associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with measurement of blood lipids and lipoproteins (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare-variant aggregate association tests using the STAAR (variant-set test for association using annotation information) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare-coding variants in nearby protein-coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500-kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variation and rare protein-coding variation at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNAs.

Keywords: association; blood lipid; cholesterol; lncRNA; rare variants; whole-genome sequencing.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests P.N. reports research grants from Allelica, Apple, Amgen, Boston Scientific, Genentech/Roche, and Novartis; personal fees from Allelica, Apple, AstraZeneca, Blackstone Life Sciences, Eli Lilly & Co, Foresite Labs, Genentech/Roche, GV, HeartFlow, Magnet Biomedicine, and Novartis; scientific advisory board membership of Esperion Therapeutics, Preciseli, and TenSixteen Bio; scientific co-founder of TenSixteen Bio; equity in MyOme, Preciseli, and TenSixteen Bio; and spousal employment at Vertex Pharmaceuticals, all unrelated to the present work. B.M.P. serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. L.M.R., S.S.R., and R.M. are consultants for the TOPMed Administrative Coordinating Center (through Westat). M.E.M. receives funding from Regeneron Pharmaceutical Inc. unrelated to this work. X. Lin is a consultant of AbbVie Pharmaceuticals and Verily Life Sciences. P.T.E. receives sponsored research support from Bayer AG, IBM Research, Bristol Myers Squibb, Pfizer, and Novo Nordisk; he has also served on advisory boards or consulted for Bayer AG, MyoKardia, and Novartis. A.P.C. previously received investigator-initiated grant support from Amgen, Inc. unrelated to the present work.

Figures

**Figure 1**
A schematic illustration of the study We performed the rare-variant association tests of 165,000 curated lncRNA genes with lipid phenotypes (i.e., LDL-C, HDL-C, TC, and TG) using the TOPMed freeze 8 data. A total of 66,329 participants from 21 studies with WGS and measured blood lipid levels were analyzed using STAAR framework. We further conducted a series of conditional analyses adjusting for known lipid GWAS variants and the nearby protein-coding genes (rare nonsynonymous, rare synonymous, and rare pLoF variants, separately). We replicated the results using an independent UKB WGS cohort. Finally, gene expression levels of the significantly lipid-associated lncRNAs were investigated in FHS RNA-seq data. TOPMed, Trans-Omics for Precision Medicine; UKB, UK Biobank; FHS, Framingham Heart Study; GLGC, Global Lipids Genetics Consortium; HDL-C, high-density lipoprotein cholesterol; LDL-C, low-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; lncRNA, long non-coding RNA; GWAS, genome wide association study; STAAR, variant-set test for association using annotation information; pLoF, predicted loss-of-function; MAF, minor allele frequency; SNVs, single-nucleotide variants.

**Figure 2**
Significantly associated lncRNAs with four blood lipid traits The significantly associated lncRNA genes (STAAR-O p value< 4.5 × 10⁻⁰⁷) are ordered by chromosome, followed by genomic positions. Dots in red and blue represent the −log₁₀(STAAR-O p value) of the STAAR unconditional and conditional analysis adjusting for known lipid-associated GWAS variants, respectively. The black dashed line is the Bonferroni correction level of 0.05/83 = 6.0 × 10⁻⁰⁴. Arrows indicate at least 10⁴-fold change of STAAR-O p values comparing the unconditional analysis and conditional analysis adjusting for known lipid-associated GWAS variants.

**Figure 3**
lncRNAs in theAPOE region associated with LDL-C Upper shows the −log₁₀(STAAR-O p value) of the STAAR unconditional analysis, STAAR conditional analysis adjusting on known lipid GWAS variants, and STAAR conditional analysis adjusting for rare non-synonymous variants within the closest protein-coding gene and nearby genes associated with monogenic lipid disorders. The bottom is the nearby protein-coding genes with the genomic coordinates. The vertical dashed line is the position of the known GWAS variants that were conditioned on. The black horizontal dashed line is the Bonferroni correction level of 0.05/111,550 = 4.5 × 10⁻⁰⁷, and the gray horizontal dashed line is the Bonferroni correction level of 0.05/83 = 6.0 × 10⁻⁰⁴.

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Update of

Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed Whole Genome Sequencing Study.
Wang Y, Selvaraj MS, Li X, Li Z, Holdcraft JA, Arnett DK, Bis JC, Blangero J, Boerwinkle E, Bowden DW, Cade BE, Carlson JC, Carson AP, Chen YI, Curran JE, de Vries PS, Dutcher SK, Ellinor PT, Floyd JS, Fornage M, Freedman BI, Gabriel S, Germer S, Gibbs RA, Guo X, He J, Heard-Costa N, Hildalgo B, Hou L, Irvin MR, Joehanes R, Kaplan RC, Kardia SL, Kelly TN, Kim R, Kooperberg C, Kral BG, Levy D, Li C, Liu C, Lloyd-Jone D, Loos RJ, Mahaney MC, Martin LW, Mathias RA, Minster RL, Mitchell BD, Montasser ME, Morrison AC, Murabito JM, Naseri T, O'Connell JR, Palmer ND, Preuss MH, Psaty BM, Raffield LM, Rao DC, Redline S, Reiner AP, Rich SS, Ruepena MS, Sheu WH, Smith JA, Smith A, Tiwari HK, Tsai MY, Viaud-Martinez KA, Wang Z, Yanek LR, Zhao W; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Rotter JI, Lin X, Natarajan P, Peloso GM.Wang Y, et al.medRxiv [Preprint]. 2023 Jun 29:2023.06.28.23291966. doi: 10.1101/2023.06.28.23291966.medRxiv. 2023.Update in:Am J Hum Genet. 2023 Oct 5;110(10):1704-1717. doi: 10.1016/j.ajhg.2023.09.003.PMID:37425772Free PMC article.Updated.Preprint.

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Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

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Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed whole-genome sequencing study

Authors

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Abstract

Conflict of interest statement

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Update of

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