Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links

PLoS Genetics

Volumn 10, Issue 2, 2014, Pages

  Rueedi, Rico ^a,b   Ledda, Mirko ^c   Nicholls, Andrew W ^d   Salek, Reza M ^e,f   Marques Vidal, Pedro ^g   Morya, Edgard ^h,i   Sameshima, Koichi ^j   Montoliu, Ivan ^c   Da Silva, Laeticia ^c   Collino, Sebastiano ^c   Martin, François Pierre ^c   Rezzi, Serge ^c   Steinbeck, Christoph ^e   Waterworth, Dawn M ^k   Waeber, Gérard ^l   Vollenweider, Peter ^l   Beckmann, Jacques S ^a,b,l   Le Coutre, Johannes ^c,m   Mooser, Vincent ^l   Bergmann, Sven ^a,b   Genick, Ulrich K ^c   Kutalik, Zoltán ^a,b,g   more..

^a UNIVERSITY OF LAUSANNE   (Switzerland)

^b SWISS INSTITUTE OF BIOINFORMATICS   (Switzerland)

^c NESTLÉ RESEARCH CENTER   (Switzerland)

^d GLAXOSMITHKLINE   (United Kingdom)

^e EUROPEAN BIOINFORMATICS INSTITUTE   (United Kingdom)

^f UNIVERSITY OF CAMBRIDGE   (United Kingdom)

^g UNIVERSITY OF LAUSANNE   (Switzerland)

^h Education and Research Center Siacute rio Libanês Hospital   (Brazil)

ⁱ Edmond and Lily Safra International Institute of Neuroscience of Natal   (Brazil)

^j UNIVERSITY OF SÃO PAULO   (Brazil)

^k GLAXOSMITHKLINE   (United States)

^l LAUSANNE UNIVERSITY HOSPITAL   (Switzerland)

^m UNIVERSITY OF TOKYO   (Japan)

more..

Author keywords

[No Author keywords available]

Indexed keywords

FUCOSYLTRANSFERASE; AMINO ACID TRANSPORTER; GALACTOSIDE 2-ALPHA-L-FUCOSYLTRANSFERASE; SLC7A9 PROTEIN, HUMAN;

ARTICLE; BRAZIL; CROHN DISEASE; ETHNICITY; FUT2 GENE; GENE LOCUS; GENE MAPPING; GENE MUTATION; GENETIC ANALYSIS; GENETIC ASSOCIATION; GENETIC CODE; GENETIC TRAIT; HUMAN; KIDNEY INJURY; MAJOR CLINICAL STUDY; METABOLIC DISORDER; METABOLOMICS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; SINGLE NUCLEOTIDE POLYMORPHISM; SLC7A9 GENE; URINALYSIS; ANIMAL; GENETICS; KIDNEY DISEASE; MALE; METABOLISM; METABOLOME; MOUSE; URINE;

AMINO ACID TRANSPORT SYSTEMS, BASIC; ANIMALS; CROHN DISEASE; FUCOSYLTRANSFERASES; GENOME-WIDE ASSOCIATION STUDY; HUMANS; KIDNEY DISEASES; MAGNETIC RESONANCE SPECTROSCOPY; MALE; METABOLOME; METABOLOMICS; MICE; POLYMORPHISM, SINGLE NUCLEOTIDE; URINE;

EID: 84901742293     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1004132     Document Type: Article

References (58)

1. LaFramboise T, (2009) Single nucleotide polymorphism arrays: a decade of biological, computational and technological advances. Nucleic Acids Res 37: 4181-4193.
2. Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, et al. (2011) Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478: 103-109.
3. Barrett JC, Clayton DG, Concannon P, Akolkar B, Cooper JD, et al. (2009) Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nat Genet 41: 703-707.
4. Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, et al. (2010) Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet 42: 937-948.
5. Patsopoulos NA, Esposito F, Reischl J, Lehr S, Bauer D, et al. (2011) Genome-wide meta-analysis identifies novel multiple sclerosis susceptibility loci. Ann Neurol 70: 897-912.
6. Ellinghaus D, Ellinghaus E, Nair RP, Stuart PE, Esko T, et al. (2012) Combined analysis of genome-wide association studies for Crohn disease and psoriasis identifies seven shared susceptibility loci. Am J Hum Genet 90: 636-647.
7. Montgomery SB, Sammeth M, Gutierrez-Arcelus M, Lach RP, Ingle C, et al. (2010) Transcriptome genetics using second generation sequencing in a Caucasian population. Nature 464: 773-777.
8. Stranger BE, Nica AC, Forrest MS, Dimas A, Bird CP, et al. (2007) Population genomics of human gene expression. Nat Genet 39: 1217-1224.
9. Gieger C, Geistlinger L, Altmaier E, Hrabe de Angelis M, Kronenberg F, et al. (2008) Genetics meets metabolomics: a genome-wide association study of metabolite profiles in human serum. PLoS Genet 4: e1000282.
10. Illig T, Gieger C, Zhai G, Romisch-Margl W, Wang-Sattler R, et al. (2010) A genome-wide perspective of genetic variation in human metabolism. Nat Genet 42: 137-141.
11. Suhre K, Shin SY, Petersen AK, Mohney RP, Meredith D, et al. (2011) Human metabolic individuality in biomedical and pharmaceutical research. Nature 477: 54-60.
12. Suhre K, Wallaschofski H, Raffler J, Friedrich N, Haring R, et al. (2011) A genome-wide association study of metabolic traits in human urine. Nat Genet 43: 565-569.
13. Montoliu I, Genick U, Ledda M, Collino S, Martin FP, et al. (2012) Current status on genome-metabolome-wide associations: an opportunity in nutrition research. Genes Nutr 8 (1) (): 19-27.
14. Homuth G, Teumer A, Volker U, Nauck M, (2012) A description of large-scale metabolomics studies: increasing value by combining metabolomics with genome-wide SNP genotyping and transcriptional profiling. J Endocrinol 215: 17-28.
15. Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, et al. (2009) Finding the missing heritability of complex diseases. Nature 461: 747-753.
16. Nica AC, Montgomery SB, Dimas AS, Stranger BE, Beazley C, et al. (2010) Candidate causal regulatory effects by integration of expression QTLs with complex trait genetic associations. PLoS Genet 6: e1000895.
17. Suhre K, Gieger C, (2012) Genetic variation in metabolic phenotypes: study designs and applications. Nat Rev Genet 13: 759-769.
18. Kettunen J, Tukiainen T, Sarin AP, Ortega-Alonso A, Tikkanen E, et al. (2012) Genome-wide association study identifies multiple loci influencing human serum metabolite levels. Nat Genet 44: 269-276.
19. Wang-Sattler R, Yu Z, Herder C, Messias AC, Floegel A, et al. (2012) Novel biomarkers for pre-diabetes identified by metabolomics. Mol Syst Biol 8: 615.
20. Dumas ME, Wilder SP, Bihoreau MT, Barton RH, Fearnside JF, et al. (2007) Direct quantitative trait locus mapping of mammalian metabolic phenotypes in diabetic and normoglycemic rat models. Nat Genet 39: 666-672.
21. Robinette SL, Holmes E, Nicholson JK, Dumas ME, (2012) Genetic determinants of metabolism in health and disease: from biochemical genetics to genome-wide associations. Genome Med 4: 30.
22. Nicholson G, Rantalainen M, Li JV, Maher AD, Malmodin D, et al. (2011) A genome-wide metabolic QTL analysis in Europeans implicates two loci shaped by recent positive selection. PLoS Genet 7: e1002270.
23. Genick UK, Kutalik Z, Ledda M, Destito MC, Souza MM, et al. (2011) Sensitivity of genome-wide-association signals to phenotyping strategy: the PROP-TAS2R38 taste association as a benchmark. PLoS One 6: e27745.
24. Ledda M, Kutalik Z, Souza Destito MC, Souza MM, Cirillo CA, et al. (2014) GWAS of human bitter taste perception identifies new loci and reveals additional complexity of bitter taste genetics. Hum Mol Genet 23: 259-267.
25. Kutalik Z, Benyamin B, Bergmann S, Mooser V, Waeber G, et al. (2011) Genome-wide association study identifies two loci strongly affecting transferrin glycosylation. Hum Mol Genet 20: 3710-3717.
26. Ehret GB, Lamparter D, Hoggart CJ, Whittaker JC, Beckmann JS, et al. (2012) A multi-SNP locus-association method reveals a substantial fraction of the missing heritability. Am J Hum Genet 91: 863-871.
27. McGovern DP, Jones MR, Taylor KD, Marciante K, Yan X, et al. (2010) Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn's disease. Hum Mol Genet 19: 3468-3476.
28. Rausch P, Rehman A, Kunzel S, Hasler R, Ott SJ, et al. (2011) Colonic mucosa-associated microbiota is influenced by an interaction of Crohn disease and FUT2 (Secretor) genotype. Proc Natl Acad Sci U S A 108: 19030-19035.
29. Ferrer-Admetlla A, Sikora M, Laayouni H, Esteve A, Roubinet F, et al. (2009) A natural history of FUT2 polymorphism in humans. Mol Biol Evol 26: 1993-2003.
30. Pacheco AR, Curtis MM, Ritchie JM, Munera D, Waldor MK, et al. (2012) Fucose sensing regulates bacterial intestinal colonization. Nature 492: 113-117.
31. Coyne MJ, Reinap B, Lee MM, Comstock LE, (2005) Human symbionts use a host-like pathway for surface fucosylation. Science 307: 1778-1781.
32. Hooper LV, Gordon JI, (2001) Commensal host-bacterial relationships in the gut. Science 292: 1115-1118.
33. Morgan XC, Tickle TL, Sokol H, Gevers D, Devaney KL, et al. (2012) Dysfunction of the intestinal microbiome in inflammatory bowel disease and treatment. Genome Biology 13: R79.
34. Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, et al. (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 42: 1118-1125.
35. Stephens NS, Siffledeen J, Su X, Murdoch TB, Fedorak RN, et al. (2012) Urinary NMR metabolomic profiles discriminate inflammatory bowel disease from healthy. J Crohns Colitis.
36. Lin HM, Barnett MP, Roy NC, Joyce NI, Zhu S, et al. (2010) Metabolomic analysis identifies inflammatory and noninflammatory metabolic effects of genetic modification in a mouse model of Crohn's disease. J Proteome Res 9: 1965-1975.
37. Lin HM, Edmunds SI, Helsby NA, Ferguson LR, Rowan DD, (2009) Nontargeted urinary metabolite profiling of a mouse model of Crohn's disease. J Proteome Res 8: 2045-2057.
38. Feliubadalo L, Font M, Purroy J, Rousaud F, Estivill X, et al. (1999) Non-type I cystinuria caused by mutations in SLC7A9, encoding a subunit (bo,+AT) of rBAT. Nat Genet 23: 52-57.
39. Kottgen A, Pattaro C, Boger CA, Fuchsberger C, Olden M, et al. (2010) New loci associated with kidney function and chronic kidney disease. Nat Genet 42: 376-384.
40. D. J. Balding MJB, Cannings C, editor (2007) Handbook of statistical genetics. Chichester: John Wiley & Sons.
41. Sheehan NA, Didelez V, Burton PR, Tobin MD, (2008) Mendelian randomisation and causal inference in observational epidemiology. PLoS Med 5: e177.
42. Glymour MM, Tchetgen EJ, Robins JM, (2012) Credible Mendelian randomization studies: approaches for evaluating the instrumental variable assumptions. Am J Epidemiol 175: 332-339.
43. Ala-Korpela M, Kangas AJ, Soininen P, (2012) Quantitative high-throughput metabolomics: a new era in epidemiology and genetics. Genome Med 4: 36.
44. Wishart DS, (2008) Quantitative metabolomics using NMR. Trends in Analytical Chemistry 27: 228-237.
45. Gall WE, Beebe K, Lawton KA, Adam KP, Mitchell MW, et al. (2010) alpha-hydroxybutyrate is an early biomarker of insulin resistance and glucose intolerance in a nondiabetic population. PLoS One 5: e10883.
46. Fiehn O, Garvey WT, Newman JW, Lok KH, Hoppel CL, et al. (2010) Plasma metabolomic profiles reflective of glucose homeostasis in non-diabetic and type 2 diabetic obese African-American women. PLoS One 5: e15234.
47. Krumsiek J, Suhre K, Evans AM, Mitchell MW, Mohney RP, et al. (2012) Mining the unknown: a systems approach to metabolite identification combining genetic and metabolic information. PLoS Genet 8: e1003005.
48. Affymetrix (2006) BRLMM: an improved genotype calling method for the GeneChip© Human Mapping 500 K array set. pp. 1-18.
49. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, et al. (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81: 559-575.
50. Marchini J, Howie B, Myers S, McVean G, Donnelly P, (2007) A new multipoint method for genome-wide association studies by imputation of genotypes. Nat Genet 39: 906-913.
51. De Meyer T, Sinnaeve D, Van Gasse B, Tsiporkova E, Rietzschel ER, et al. (2008) NMR-based characterization of metabolic alterations in hypertension using an adaptive, intelligent binning algorithm. Anal Chem 80: 3783-3790.
52. Anderson P, Mahle D, Doom T, Reo N, DelRaso N, et al. (2010) Dynamic adaptive binning: an improved quantification technique. Metabolomics.
53. Collino S, Montoliu I, Martin FP, Scherer M, Mari D, et al. (2013) Metabolic signatures of extreme longevity in northern italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PLoS One 8: e56564.
54. Claus SP, Ellero SL, Berger B, Krause L, Bruttin A, et al. (2011) Colonization-induced host-gut microbial metabolic interaction. MBio 2: e00271-00210.
55. Staab JM, O'Connell TM, Gomez SM, (2010) Enhancing metabolomic data analysis with Progressive Consensus Alignment of NMR Spectra (PCANS). BMC Bioinformatics 11: 123.
56. Kohl SM, Klein MS, Hochrein J, Oefner PJ, Spang R, et al. (2012) State-of-the art data normalization methods improve NMR-based metabolomic analysis. Metabolomics 8: 146-160.
57. Gao X, Starmer J, Martin ER, (2008) A multiple testing correction method for genetic association studies using correlated single nucleotide polymorphisms. Genet Epidemiol 32: 361-369.
58. Lawlor DA, Harbord RM, Sterne JA, Timpson N, Davey Smith G, (2008) Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat Med 27: 1133-1163.