Trial reportCirculation. Cardiovascular genetics2015
Association of Rare Loss-Of-Function Alleles in HAL, Serum Histidine: Levels and Incident Coronary Heart Disease.
Open access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph
Trial report in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 5% of its field
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.
- Use of Mendelian Randomization to Unveil Metabolic Markers inJournal of Korean medical science · 2026Pooled it
- Threonine in Coronary Artery Disease: Insights From Metabolic Syndrome Amino Acid Profiling.Medical science monitor : international medical journal of experimental and clinical research · 2026Article
- Circulating imidazole propionate and coronary heart disease risk: interplay between histidine intake, fiber, and gut microbiome.BMC medicine · 2026Article
- MELODY: Mediation Analysis in Logistic Regression for High-Dimensional Mediators and a Binary Outcome.Genetic epidemiology · 2026Article
- Application of Mendelian randomization to explore metabolic pathways in colorectal cancer.Annals of medicine and surgery (2012) · 2025Article
- Histidine ammonia lyase expression characteristics in primary liver cancer: hepatocellular carcinoma and cholangiocarcinoma.Discover oncology · 2025Article
- MELODY: Mediation Analysis in Logistic Regression for High-Dimensional Mediators and a Binary Outcome.bioRxiv : the preprint server for biology · 2025Article
- Metabolic Signatures of Blood Pressure and Risk of Cardiovascular Diseases.Journal of the American Heart Association · 2024Article
- The inverse associations of glycine and histidine in diet with hyperlipidemia and hypertension.Nutrition journal · 2024Article
- Magnetic Titanium Dioxide Nanocomposites as a Recyclable SERRS Substrate for the Ultrasensitive Detection of Histidine.Molecules (Basel, Switzerland) · 2024Article
- Modulation Effects ofFoods (Basel, Switzerland) · 2023Article
- Associations of Histamine Metabolites with Disease Severity and Mortality in Pulmonary Arterial Hypertension.Annals of the American Thoracic Society · 2023Article
- The self-assembly of L-histidine might be the cause of histidinemia.Scientific reports · 2023Article
- Identification of prognostic and diagnostic signatures for cancer and acute myocardial infarction: multi-omics approaches for deciphering heterogeneity to enhance patient management.Frontiers in pharmacology · 2023Article
- Metabolomics study of blood pressure salt-sensitivity and hypertension.Nutrition, metabolism, and cardiovascular diseases : NMCD · 2022Article
- A Newly Developed Indicator of Overeating Saturated Fat Based on Serum Fatty Acids and Amino Acids and Its Association With Incidence of Type 2 Diabetes: Evidence From Two Randomized Controlled Feeding Trials and a Prospective Study.Frontiers in nutrition · 2022Article
- The Association of 9 Amino Acids With Cardiovascular Events in Finnish Men in a 12-Year Follow-up Study.The Journal of clinical endocrinology and metabolism · 2021Article
- Metabolomics as a Tool to Investigate HIV/TB Co-Infection.Frontiers in molecular biosciences · 2021Review
- Pi-Dan-Jian-Qing Decoction Ameliorates Type 2 Diabetes Mellitus Through Regulating the Gut Microbiota and Serum Metabolism.Frontiers in cellular and infection microbiology · 2021Article
- Influence of Histidine Administration on Ammonia and Amino Acid Metabolism: A Review.Physiological research · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 7 institutions in 2 countries.
Bing YuFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Alexander H LiFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Donna MuznyFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Narayanan VeeraraghavanFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Paul S de VriesFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Joshua C BisFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Solomon K MusaniFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Danny AlexanderFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Alanna C MorrisonFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Oscar H FrancoFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
André UitterlindenFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Albert HofmanFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Abbas DehghanFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
James G WilsonFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Bruce M PsatyFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Richard GibbsFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Peng WeiFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).
Eric BoerwinkleFrom the Human Genetics Center (B.Y., A.H.L., A.C.M., P.W., E.B.) and Division of Biostatistics (P.W.), School of Public Health, University of Texas Health Science Center at Houston; Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX (D.M., N.V., R.G., E.B.); Department of Epidemiology (P.S.d.V., O.H.F., A.U., A.H., A.D.) and Department of Internal Medicine (A.U.), Erasmus MC, Rotterdam, the Netherlands; Cardiovascular Health Research Unit (J.C.B., B.M.P.), Department of Epidemiology (B.M.P.), and Department of Health Services (B.M.P.), University of Washington, Seattle; Jackson Heart Study (S.K.M.) and Department of Physiology and Biophysics (J.G.W.), University of Mississippi Medical Center Jackson, Metabolon, Inc., Durham, NC (D.A.); and Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.). Eric.Boerwinkle@uth.tmc.edu.
Jackson Memorial Hospital · USMetabolon (United States) · USErasmus MC · NLKaiser Permanente Washington Health Research Institute · USUniversity of Mississippi Medical Center · USErasmus University Rotterdam · NLGroup Health Cooperative · US
Funding
The Human Genome Sequencing CenterU54HG003273 · NHGRI · BAYLOR COLLEGE OF MEDICINE · PI GIBBS, RICHARD A · 2004 to 2015
$341.3MUCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI ALAN R. SALTIEL · 2003 to 2026
$40.4MBuilding on GWAS for NHLBI-disease: the CHARGE consortiumRC2HL102419 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI BOERWINKLE, ERIC A. · 2009 to 2010
$27.6MGenome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2MMULTIDISCIPLINARY RESEARCH TRAINING IN CARDIOLOGYT32HL007208 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Patrick Thomas Ellinor, David E Sosnovik · 1985 to 2026
$16.1MBaylor-Johns Hopkins Center for Mendelian GeneticsU54HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2012 to 2015
$15.6MBaylor-Johns Hopkins Center for Mendelian GeneticsUM1HG006542 · NHGRI · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 2016 to 2020
$14.5MCenter for Clinical and Translational Sciences (CCTS)UL1TR000371 · NCATS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MCPHERSON, DAVID D · 2012 to 2016
$13.4MEpidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MNCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCATS NIH HHS UL1 TR000371NHGRI NIH HHS HG003273NHGRI NIH HHS HG004402NHGRI NIH HHS HG006542NHGRI NIH HHS U01 HG004402NHGRI NIH HHS U01HG004402NHGRI NIH HHS U54 HG003273NHGRI NIH HHS U54 HG006542NHGRI NIH HHS UM1 HG006542NHLBI NIH HHS HHSN268200800007CNHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201200036CNHLBI NIH HHS HHSN268201300046CNHLBI NIH HHS HHSN268201300047CNHLBI NIH HHS HHSN268201300048CNHLBI NIH HHS HHSN268201300049CNHLBI NIH HHS HHSN268201300050CNHLBI NIH HHS HL068986NHLBI NIH HHS HL080295NHLBI NIH HHS HL087652NHLBI NIH HHS HL102419NHLBI NIH HHS HL103612NHLBI NIH HHS HL105756NHLBI NIH HHS HL120393NHLBI NIH HHS N01 HC025195NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS N01-HC-25195NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL068986NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL116720NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01HL59367NHLBI NIH HHS RC2 HL102419NHLBI NIH HHS T32 HL007208NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL120393NIA NIH HHS AG023629NIA NIH HHS R01 AG023629NIA NIH HHS R56 AG023629NIDDK NIH HHS DK063491NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK081572NIDDK NIH HHS R01DK081572
Abstract
backgroundHistidine is a semiessential amino acid with antioxidant and anti-inflammatory properties. Few data are available on the associations between genetic variants, histidine levels, and incident coronary heart disease (CHD) in a population-based sample. METHODS AND
resultsBy conducting whole exome sequencing on 1152 African Americans in the Atherosclerosis Risk in Communities (ARIC) study and focusing on loss-of-function (LoF) variants, we identified 3 novel rare LoF variants in HAL, a gene that encodes histidine ammonia-lyase in the first step of histidine catabolism. These LoF variants had large effects on blood histidine levels (β=0.26; P=1.2×10(-13)). The positive association with histidine levels was replicated by genotyping an independent sample of 718 ARIC African Americans (minor allele frequency=1%; P=1.2×10(-4)). In addition, high blood histidine levels were associated with reduced risk of developing incident CHD with an average of 21.5 years of follow-up among African Americans (hazard ratio=0.18; P=1.9×10(-4)). This finding was validated in an independent sample of European Americans from the Framingham Heart Study (FHS) Offspring Cohort. However, LoF variants in HAL were not directly significantly associated with incident CHD after meta-analyzing results from the CHARGE Consortium.
conclusionsThree LoF mutations in HAL were associated with increased histidine levels, which in turn were shown to be inversely related to the risk of CHD among both African Americans and European Americans. Future investigations on the association between HAL gene variation and CHD are warranted.
Indexed as
AllelesCoronary DiseaseMutationAdultBlack or African AmericanFemaleHistidineHistidine Ammonia-LyaseHumansMaleWhite PeopleHistidineHistidine Ammonia-Lyasecoronary diseasehistidinehistidine ammonia-lyase
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