Plasma metabolomic profiles enhance precision medicine for volunteers of normal health

Proceedings of the National Academy of Sciences of the United States of America

Volumn 112, Issue 35, 2015, Pages E4901-E4910

  Guoa, Lining ^a   Milburna, Michael V ^a   Ryalsa, John A ^a   Lonergana, Shaun C ^a   Mitchella, Matthew W ^a   Wulffa, Jacob E ^a   Alexandera, Danny C ^a   Evansa, Anne M ^a   Bridgewatera, Brandi ^a   Millera, Luke ^a   Gonzalez Garay, Manuel L ^b   Caskey, C Thomas ^c  

^a METABOLON INC   (United States)

^b UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^c BAYLOR COLLEGE OF MEDICINE   (United States)

Author keywords

Disease assessment; Functional phenotyping; Gene penetrance; Metabolomics; Whole exome sequencing

Indexed keywords

3 HYDROXYBUTYRIC ACID; 3 METHYLHISTIDINE; GLUCOSE; GLYCINE; ISOLEUCINE; LEUCINE; PALMITOYLCARNITINE; STEAROYLCARNITINE; VALINE; XENOBIOTIC AGENT;

ACCURACY; ADULT; ARTICLE; BIOSYNTHESIS; BLOOD ANALYSIS; CARNITINE DEFICIENCY; CATABOLISM; DIABETES MELLITUS; DRUG EFFECT; DRUG EFFICACY; DRUG RESPONSE; ENERGY METABOLISM; FEMALE; GENE MUTATION; GENE SEQUENCE; GENETIC RISK; HEREDITARY FRUCTOSE INTOLERANCE; HEREDITY; HUMAN; INTESTINE FLORA; LIVER DYSFUNCTION; MAJOR CLINICAL STUDY; MALE; MASS FRAGMENTOGRAPHY; METABOLITE; METABOLOMICS; PEDIGREE; PERSONALIZED MEDICINE; PHENOTYPE; PRECISION MEDICINE; PRIORITY JOURNAL; RISK ASSESSMENT; TANDEM MASS SPECTROMETRY; THERAPY EFFECT; XANTHINURIA; COHORT ANALYSIS; LIQUID CHROMATOGRAPHY; METABOLOME; NORMAL HUMAN; PLASMA;

CHROMATOGRAPHY, LIQUID; COHORT STUDIES; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; HEALTHY VOLUNTEERS; HUMANS; METABOLOME; PLASMA; PRECISION MEDICINE;

EID: 84940974070     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1508425112     Document Type: Article

References (63)

1. Yang Y, et al. (2013) Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 369(16):1502-1511.
2. Berg JS, et al. (2011) Next generation massively parallel sequencing of targeted exomes to identify genetic mutations in primary ciliary dyskinesia: Implications for application to clinical testing. Genet Med 13(3):218-229.
3. Maxmen A (2011) Exome sequencing deciphers rare diseases. Cell 144(5):635-637.
4. Ng SB, et al. (2010) Exome sequencing identifies the cause of a mendelian disorder. Nat Genet 42(1):30-35.
5. Roach JC, et al. (2010) Analysis of genetic inheritance in a family quartet by whole-genome sequencing. Science 328(5978):636-639.
6. Dasouki MJ, et al. (2013) Exome sequencing reveals a thrombopoietin ligand mutation in a Micronesian family with autosomal recessive aplastic anemia. Blood 122(20):3440-3449.
7. Schaaf CP, et al. (2013) Truncating mutations of MAGEL2 cause Prader-Willi phenotypes and autism. Nat Genet 45(11):1405-1408.
8. Takeuchi F, et al. (2009) A genome-wide association study confirms VKORC1, CYP2C9, and CYP4F2 as principal genetic determinants of warfarin dose. PLoS Genet 5(3):e1000433.
9. Katsanis SH, Katsanis N (2013) Molecular genetic testing and the future of clinical genomics. Nat Rev Genet 14(6):415-426.
10. Ginsburg GS (2013) Realizing the opportunities of genomics in health care. JAMA 309(14):1463-1464.
11. Feero WG, Guttmacher AE, Collins FS (2010) Genomic medicine-An updated primer. N Engl J Med 362(21):2001-2011.
12. Bamshad MJ, et al. (2011) Exome sequencing as a tool for Mendelian disease gene discovery. Nat Rev Genet 12(11):745-755.
13. Suhre K, et al.; CARDIoGRAM (2011) Human metabolic individuality in biomedical and pharmaceutical research. Nature 477(7362):54-60.
14. Shin SY, et al.; Multiple Tissue Human Expression Resource (MuTHER) Consortium (2014) An atlas of genetic influences on human blood metabolites. Nat Genet 46(6):543-550.
15. Milburn MV, Lawton KA (2013) Application of metabolomics to diagnosis of insulin resistance. Annu Rev Med 64:291-305.
16. Langley RJ, et al. (2013) An integrated clinico-metabolomic model improves prediction of death in sepsis. Sci Transl Med 5(195):195ra95.
17. Menni C, et al. (2013) Metabolomic markers reveal novel pathways of ageing and early development in human populations. Int J Epidemiol 42(4):1111-1119.
18. Zhang Y, et al. (2011) Detrimental effects of adenosine signaling in sickle cell disease. Nat Med 17(1):79-86.
19. Yu B, et al. (2013) Genome-wide association study of a heart failure related metabolomic profile among African Americans in the Atherosclerosis Risk in Communities (ARIC) study. Genet Epidemiol 37(8):840-845.
20. Zheng Y, et al. (2013) Metabolomics and incident hypertension among blacks: The atherosclerosis risk in communities study. Hypertension 62(2):398-403.
21. Gieger C, et al. (2008) Genetics meets metabolomics: A genome-wide association study of metabolite profiles in human serum. PLoS Genet 4(11):e1000282.
22. Shah SH, Kraus WE, Newgard CB (2012) Metabolomic profiling for the identification of novel biomarkers and mechanisms related to common cardiovascular diseases: form and function. Circulation 126(9):1110-1120.
23. Evans AM, DeHaven CD, Barrett T, Mitchell M, Milgram E (2009) 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(16):6656-6667.
24. Gonzalez-Garay ML, McGuire AL, Pereira S, Caskey CT (2013) Personalized genomic disease risk of volunteers. Proc Natl Acad Sci USA 110(42):16957-16962.
25. Nicholson JK, et al. (2012) Host-gut microbiota metabolic interactions. Science 336(6086):1262-1267.
26. Stenson PD, et al. (2009) The Human Gene Mutation Database: 2008 update. Genome Med 1(1):13.
27. Boulieu R, Bory C, Baltassat P, Divry P (1984) Hypoxanthine and xanthine concentrations determined by high performance liquid chromatography in biological fluids from patients with xanthinuria. Clin Chim Acta 142(1):83-89.
28. Bennett MJ, Carpenter KH, Hill PG (1985) Asymptomatic xanthinuria detected as a result of routine analysis of serum for urate. Clin Chem 31(3):492.
29. Steinmann B, Baerlocher K, Gitzelmann R (1975) [Hereditary disorders of fructose metabolism. Loading tests with fructose, sorbitol and dihydroxyacetone]. Nutr Metab 18(Suppl 1):115-132. German.
30. Alexander D, Lombardi R, Rodriguez G, Mitchell MM, Marian AJ (2011) Metabolomic distinction and insights into the pathogenesis of human primary dilated cardiomyopathy. Eur J Clin Invest 41(5):527-538.
31. Long CL, Dillard DR, Bodzin JH, Geiger JW, Blakemore WS (1988) Validity of 3-methylhistidine excretion as an indicator of skeletal muscle protein breakdown in humans. Metabolism 37(9):844-849.
32. Russell DW (2003) The enzymes, regulation, and genetics of bile acid synthesis. Annu Rev Biochem 72:137-174.
33. Hofmann AF (2009) The enterohepatic circulation of bile acids in mammals: Form and functions. Front Biosci (Landmark Ed) 14:2584-2598.
34. Barnes S, Gallo GA, Trash DB, Morris JS (1975) Diagnostic value of serum bile acid estimations in liver disease. J Clin Pathol 28(6):506-509.
35. Bouchier IA, Pennington CR (1978) Serum bile acids in hepatobiliary disease. Gut 19(6):492-496.
36. Kalhan SC, et al. (2011) Plasma metabolomic profile in nonalcoholic fatty liver disease. Metabolism 60(3):404-413.
37. Hartley JL, et al. (2010) Mutations in TTC37 cause trichohepatoenteric syndrome (phenotypic diarrhea of infancy). Gastroenterology 138(7):2388-2398, 2398.e1-2398.e2.
38. Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307(5708):384-387.
39. Ferrannini E, et al. (2013) Early metabolic markers of the development of dysglycemia and type 2 diabetes and their physiological significance. Diabetes 62(5):1730-1737.
40. Yamanouchi T, et al. (1996) Clinical usefulness of serum 1,5-anhydroglucitol in monitoring glycaemic control. Lancet 347(9014):1514-1518.
41. Newgard CB, et al. (2009) A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 9(4):311-326.
42. Perseghin G, Ghosh S, Gerow K, Shulman GI (1997) Metabolic defects in lean nondiabetic offspring of NIDDM parents: A cross-sectional study. Diabetes 46(6):1001-1009.
43. Weyrich P, et al. (2009) Genetic variability of procolipase associates with altered insulin secretion in non-diabetic Caucasians. Exp Clin Endocrinol Diabetes 117(2):83-87.
44. Simonis-Bik AM, et al. (2010) Gene variants in the novel type 2 diabetes loci CDC123/ CAMK1D, THADA, ADAMTS9, BCL11A, and MTNR1B affect different aspects of pancreatic beta-cell function. Diabetes 59(1):293-301.
45. Waeber G, et al. (2000) The gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes. Nat Genet 24(3):291-295.
46. Vaisse C, et al. (2000) Melanocortin-4 receptor mutations are a frequent and heterogeneous cause of morbid obesity. J Clin Invest 106(2):253-262.
47. Zanger UM, Schwab M (2013) Cytochrome P450 enzymes in drug metabolism: Regulation of gene expression, enzyme activities, and impact of genetic variation. Pharmacol Ther 138(1):103-141.
48. Larson AM, et al.; Acute Liver Failure Study Group (2005) Acetaminophen-induced acute liver failure: Results of a United States multicenter, prospective study. Hepatology 42(6):1364-1372.
49. James LP, Mayeux PR, Hinson JA (2003) Acetaminophen-induced hepatotoxicity. Drug Metab Dispos 31(12):1499-1506.
50. Yamazaki M, et al. (2013) Perturbation of bile acid homeostasis is an early pathogenesis event of drug induced liver injury in rats. Toxicol Appl Pharmacol 268(1):79-89.
51. Thompson PD, Clarkson P, Karas RH (2003) Statin-associated myopathy. JAMA 289(13): 1681-1690.
52. Niemi M (2010) Transporter pharmacogenetics and statin toxicity. Clin Pharmacol Ther 87(1):130-133.
53. von Moltke LL, et al. (2004) Inhibition of human cytochromes P450 by components of Ginkgo biloba. J Pharm Pharmacol 56(8):1039-1044.
54. Jacob HJ (2013) Next-generation sequencing for clinical diagnostics. N Engl J Med 369(16):1557-1558.
55. Yang Y, et al. (2014) Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312(18):1870-1879.
56. Cooper DN, Krawczak M, Polychronakos C, Tyler-Smith C, Kehrer-Sawatzki H (2013) Where genotype is not predictive of phenotype: Towards an understanding of the molecular basis of reduced penetrance in human inherited disease. Hum Genet 132(10):1077-1130.
57. Adamski J, Suhre K (2013) Metabolomics platforms for genome wide association studies-Linking the genome to the metabolome. Curr Opin Biotechnol 24(1):39-47.
58. de Magistris L, et al. (2010) Alterations of the intestinal barrier in patients with autism spectrum disorders and in their first-degree relatives. J Pediatr Gastroenterol Nutr 51(4):418-424.
59. Coury DL, et al. (2012) Gastrointestinal conditions in children with autism spectrum disorder: developing a research agenda. Pediatrics 130(Suppl 2):S160-S168.
60. Kohane IS, et al. (2012) The co-morbidity burden of children and young adults with autism spectrum disorders. PLoS One 7(4):e33224.
61. Bitsko RH, et al. (2014) A national profile of Tourette syndrome, 2011-2012. J Dev Behav Pediatr 35(5):317-322.
62. Hsiao EY, et al. (2013) Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders. Cell 155(7):1451-1463.
63. Storey JD, Tibshirani R (2003) Statistical significance for genomewide studies. Proc Natl Acad Sci USA 100(16):9440-9445.