Loss-of-function variants influence the human serum metabolome

Science Advances

Volumn 2, Issue 8, 2016, Pages

  Yu, Bing ^a   Li, Alexander H ^a   Metcalf, Ginger A ^b   Muzny, Donna M ^b   Morrison, Alanna C ^a   White, Simon ^b   Mosley, Thomas H ^c   Gibbs, Richard A ^b   Boerwinkle, Eric ^a,b  

^a UNIVERSITY OF TEXAS   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c UNIVERSITY OF MISSISSIPPI SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIOMARKERS; BIOMOLECULES; BLOOD PRESSURE; BODY FLUIDS; CARDIOLOGY; FATTY ACIDS; GAS CHROMATOGRAPHY; GENES; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLITES;

AFRICAN AMERICAN; BIOLOGICAL PROCESS; DIAGNOSTIC BIOMARKERS; DISEASE ETIOLOGY; GENETIC DIVERSITY; INDEPENDENT SAMPLES; METABOLITE LEVEL; POPULATION STUDIES;

DIAGNOSIS;

BIOLOGICAL MARKER; SLCO1B1 PROTEIN, HUMAN; SOLUTE CARRIER ORGANIC ANION TRANSPORTER 1B1;

AFRICAN AMERICAN; AGED; BLOOD; CAUCASIAN; EXOME; FEMALE; GENETIC VARIATION; GENETICS; HEART FAILURE; HIGH THROUGHPUT SEQUENCING; HUMAN; HYPERTENSION; MALE; METABOLISM; METABOLOME; MIDDLE AGED; MUTATION; PATHOLOGY; RISK FACTOR;

AFRICAN AMERICANS; AGED; BIOMARKERS; EUROPEAN CONTINENTAL ANCESTRY GROUP; EXOME; FEMALE; GENETIC VARIATION; HEART FAILURE; HIGH-THROUGHPUT NUCLEOTIDE SEQUENCING; HUMANS; HYPERTENSION; MALE; METABOLOME; MIDDLE AGED; MUTATION; RISK FACTORS; SOLUTE CARRIER ORGANIC ANION TRANSPORTER FAMILY MEMBER 1B1;

EID: 85017420204     PISSN: None     EISSN: 23752548     Source Type: Journal    
DOI: 10.1126/sciadv.1600800     Document Type: Article

References (31)

1. K. Suhre, C. Gieger, Genetic variation in metabolic phenotypes: Study designs and applications. Nat. Rev. Genet. 13, 759–769 (2012).
2. Y.-F. Chang, J. S. Imam, M. F. Wilkinson, The nonsense-mediated decay RNA surveillance pathway. Annu. Rev. Biochem. 76, 51–74 (2007).
3. D. G. MacArthur, S. Balasubramanian, A. Frankish, N. Huang, J. Morris, K. Walter, L. Jostins, L. Habegger, J. K. Pickrell, S. B. Montgomery, C. A. Albers, Z. D. Zhang, D. F. Conrad, G. Lunter, H. Zheng, Q. Ayub, M. A. DePristo, E. Banks, M. Hu, R. E. Handsaker, J. A. Rosenfeld, M. Fromer, M. Jin, X. J. Mu, E. Khurana, K. Ye, M. Kay, G. I. Saunders, M.-M. Suner, T. Hunt, I. H. A. Barnes, C. Amid, D. R. Carvalho-Silva, A. H. Bignell, C. Snow, B. Yngvadottir, S. Bumpstead, D. N. Cooper, Y. Xue, I. G. Romero; 1000 Genomes Project Consortium, J. Wang, Y. Li, R. A. Gibbs, S. A. McCarroll, E. T. Dermitzakis, J. K. Pritchard, J. C. Barrett, J. Harrow, M. E. Hurles, M. B. Gerstein, C. Tyler-Smith, A systematic survey of loss-of-function variants in human protein-coding genes. Science 335, 823–828 (2012).
4. Myocardial Infarction Genetics Consortium Investigators, Inactivating mutations in NPC1L1 and protection from coronary heart disease. N. Engl. J. Med. 371, 2072–2082 (2014).
5. J. C. Cohen, E. Boerwinkle, T. H. Mosley Jr., H. H. Hobbs, Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N. Engl. J. Med. 354, 1264–1272 (2006).
6. A. Bonen, S. E. Campbell, C. R. Benton, A. Chabowski, S. L. M. Coort, X.-X. Han, D. P. Y. Koonen, J. F. C. Glatz, J. J. F. P. Luiken, Regulation of fatty acid transport by fatty acid translocase/CD36. Proc. Nutr. Soc. 63, 245–249 (2004).
7. D. H. Chace, S. L. Hillman, J. L. K. Van Hove, E. W. Naylor, Rapid diagnosis of MCAD deficiency: Quantitative analysis of octanoylcarnitine and other acylcarnitines in newborn blood spots by tandem mass spectrometry. Clin. Chem. 43, 2106–2113 (1997).
8. S.-Y. Shin, E. B. Fauman, A.-K. Petersen, J. Krumsiek, R. Santos, J. Huang, M. Arnold, I. Erte, V. Forgetta, T.-P. Yang, K. Walter, C. Menni, L. Chen, L. Vasquez, A. M. Valdes, C. L. Hyde, V. Wang, D. Ziemek, P. Roberts, L. Xi, E. Grundberg; Multiple Tissue Human Expression Resource (MuTher) Consortium, M. Waldenberger, J. B. Richards, R. P. Mohney, M. V. Milburn, S. L. John, J. Trimmer, F. J. Theis, J. P. Overington, K. Suhre, M. J. Brosnan, C. Gieger, G. Kastenmüller, T. D. Spector, N. Soranzo, An atlas of genetic influences on human blood metabolites. Nat. Genet. 46, 543–550 (2014).
9. SEARCH Collaborative Group, E. Link, S. Parish, J. Armitage, L. Bowman, S. Heath, F. Matsuda, I. Gut, M. Lathrop, R. Collins, SLCO1B1 variants and statin-induced myopathy—A genomewide study. N. Engl. J. Med. 359, 789–799 (2008).
10. J. E. Udelson, Heart failure with preserved ejection fraction. Circulation 124, e540–e543 (2011).
11. C. Menni, D. Graham, G. Kastenmüller, N. H. J. Alharbi, S. M. Alsanosi, M. McBride, M. Mangino, P. Titcombe, S.-Y. Shin, M. Psatha, T. Geisendorfer, A. Huber, A. Peters, R. Wang-Sattler, T. Xu, M. J. Brosnan, J. Trimmer, C. Reichel, R. P. Mohney, N. Soranzo, M. H. Edwards, C. Cooper, A. C. Church, K. Suhre, C. Gieger, A. F. Dominiczak, T. D. Spector, S. Padmanabhan, A. M. Valdes, Metabolomic identification of a novel pathway of blood pressure regulation involving hexadecanedioate. Hypertension 66, 422–499 (2015).
12. TG and HL Working Group of the Exome Sequencing Project, J. Crosby, G. M. Peloso, P. L. Auer, D. R. Crosslin, N. O. Stitziel, L. A. Lange, Y. Lu, Z. Z. Tang, H. Zhang, G. Hindy, N. Masca, K. Stirrups, S. Kanoni, R. Do, G. Jun, Y. Hu, H. M. Kang, C. Xue, A. Goel, M. Farrall, S. Duga, P. A. Merlini, R. Asselta, D. Girelli, O. Olivieri, N. Martinelli, W. Yin, D. Reilly, E. Speliotes, C. S. Fox, K. Hveem, O. L. Holmen, M. Nikpay, D. N. Farlow, T. L. Assimes, N. Franceschini, J. Robinson, K. E. North, L. W. Martin, M. DePristo, N. Gupta, S. A. Escher, J. H. Jansson, N. Van Zuydam, C. N. Palmer, N. Wareham, W. Koch, T. Meitinger, A. Peters, W. Lieb, R. Erbel, I. R. Konig, J. Kruppa, F. Degenhardt, O. Gottesman, E. P. Bottinger, C. J. O’Donnell, B. M. Psaty, C. M. Ballantyne, G. Abecasis, J. M. Ordovas, O. Melander, H. Watkins, M. Orho-Melander, D. Ardissino, R. J. Loos, R. McPherson, C. J. Willer, J. Erdmann, A. S. Hall, N. J. Samani, P. Deloukas, H. Schunkert, J. G. Wilson, C. Kooperberg, S. S. Rich, R. P. Tracy, D. Y. Lin, D. Altshuler, S. Gabriel, D. A. Nickerson, G. P. Jarvik, L. A. Cupples, A. P. Reiner, E. Boerwinkle, S. Kathiresan, Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N. Engl. J. Med. 371, 22–31 (2014).
13. M. C. Campbell, S. A. Tishkoff, African genetic diversity: Implications for human demographic history, modern human origins, and complex disease mapping. Annu. Rev. Genomics Hum. Genet. 9, 403–433 (2008).
14. The ARIC Investigators, The Atherosclerosis Risk in Communities (ARIC) Study: Design and objectives.. Am. J. Epidemiol. 129, 687–702 (1989).
15. T. Ohta, N. Masutomi, N. Tsutsui, T. Sakairi, M. Mitchell, M. V. Milburn, J. A. Ryals, K. D. Beebe, L. Guo, Untargeted metabolomic profiling as an evaluative tool of fenofibrate-induced toxicology in Fischer 344 male rats. Toxicol. Pathol. 37, 521–535 (2009).
16. A. M. Evans, C. D. DeHaven, T. Barrett, M. Mitchell, E. Milgram, Integrated, nontargeted ultrahigh performance liquid chromatography/electrospray ionization tandem mass spectrometry platform for the identification and relative quantification of the small-molecule complement of biological systems. Anal. Chem. 81, 6656–6667 (2009).
17. H. Li, R. Durbin, Fast and accurate long-read alignment with Burrows-Wheeler transform. Bioinformatics 26, 589–595 (2010).
18. D. Challis, J. Yu, U. S. Evani, A. R. Jackson, S. Paithankar, C. Coarfa, A. Milosavljevic, R. A. Gibbs, F. Yu, An integrative variant analysis suite for whole exome next-generation sequencing data. BMC Bioinformatics 13, 8 (2012).
19. K. Wang, M. Li, H. Hakonarson, ANNOVAR: Functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164 (2010).
20. X. Liu, X. Jian, E. Boerwinkle, dbNSFP v2.0: A database of human non-synonymous SNVs and their functional predictions and annotations. Hum. Mutat. 34, E2393–E2402 (2013).
21. B. Li, S. M. Leal, Methods for detecting associations with rare variants for common diseases: Application to analysis of sequence data. Am. J. Hum. Genet. 83, 311–321 (2008).
22. A. S. Levey, L. A. Stevens, C. H. Schmid, Y. L. Zhang, A. F. Castro III, H. I. Feldman, J. W. Kusek, P. Eggers, F. Van Lente, T. Greene, J. Coresh; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), A new equation to estimate glomerular filtration rate. Ann. Intern. Med. 150, 604–612 (2009).
23. D. A. Gerber, Low free serum histidine concentration in rheumatoid arthritis. A measure of disease activity. J. Clin. Invest. 55, 1164–1173 (1975).
24. B. Yu, A. H. Li, D. Muzny, N. Veeraraghavan, P. S. de Vries, J. C. Bis, S. K. Musani, D. Alexander, A. C. Morrison, O. H. Franco, A. Uitterlinden, A. Hofman, A. Dehghan, J. G. Wilson, B. M. Psaty, R. Gibbs, P. Wei, E. Boerwinkle, Association of rare loss-of-function alleles in HAL, serum histidine levels and incident coronary heart disease. Circ. Cardiovasc. Genet. 8, 351–355 (2015).
25. E. R. Stadtman, H. Van Remmen, A. Richardson, N. B. Wehr, R. L. Levine, Methionine oxidation and aging. Biochim. Biophys. Acta 1703, 135–140 (2005).
26. J. Plutzky, Peroxisome proliferator-activated receptors in vascular biology and atherosclerosis: Emerging insights for evolving paradigms. Curr. Atheroscler. Rep. 2, 327–335 (2000).
27. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106, 3143–3421 (2002).
28. H. K. Choi, D. B. Mount, A. M. Reginato, Pathogenesis of gout. Ann. Intern. Med. 143, 499–516 (2005).
29. A. Dehghan, M. van Hoek, E. J. G. Sijbrands, A. Hofman, J. C. M. Witteman, High serum uric acid as a novel risk factor for type 2 diabetes. Diabetes Care 31, 361–362 (2008).
30. M. R. Hayden, S. C. Tyagi, Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle. Nutr. Metab. 1, 10 (2004).
31. L. K. Niskanen, D. E. Laaksonen, K. Nyyssӧnen, G. Alfthan, H. M. Lakka, T. A. Lakka, J. T. Salonen, Uric acid level as a risk factor for cardiovascular and all-cause mortality in middle-aged men: A prospective cohort study. Arch. Intern. Med. 164, 1546–1551 (2004).