Insight in Genome-Wide Association of Metabolite Quantitative Traits by Exome Sequence Analyses

PLoS Genetics

Volumn 11, Issue 1, 2015, Pages

  Demirkan, Ayşe ^a,b   Henneman, Peter ^a,c   Verhoeven, Aswin ^a   Dharuri, Harish ^a   Amin, Najaf ^b   van Klinken, Jan Bert ^a   Karssen, Lennart C ^b   de Vries, Boukje ^a   Meissner, Axel ^a   Göraler, Sibel ^a   van den Maagdenberg, Arn M J M ^a   Deelder, André M ^a   C ’t Hoen, Peter A ^a   van Duijn, Cornelia M ^b   van Dijk, Ko Willems ^a  

^a LEIDEN UNIVERSITY MEDICAL CENTER   (Netherlands)

^b ERASMUS MEDICAL CENTER   (Netherlands)

^c ACADEMIC MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

3 HYDROXYBUTYRIC ACID; CARBAMOYL PHOSPHATE SYNTHASE; CARNITINE; DIMETHYLGLYCINE; DIMETHYLGLYCINE DEHYDROGENASE; GLYCINE; INWARDLY RECTIFYING POTASSIUM CHANNEL; MEMBRANE PROTEIN; PROLINE; PROLINE DEHYDROGENASE; PROLINE DEHYDROGENASE (OXIDASE) 1; PROTEIN KCNJ16; PROTEIN SLC16A9; PYRUVIC ACID; TRANSITION PROTEIN 1; UNCLASSIFIED DRUG; VALINE;

ADULT; ARTICLE; CHROMOSOME 2P; COHORT ANALYSIS; CONTROLLED STUDY; CPS1 GENE; CROSS-SECTIONAL STUDY; DMGDH GENE; EXOME; GENE LOCUS; GENETIC ASSOCIATION; GENETIC HETEROGENEITY; GENETIC VARIABILITY; HAPLOTYPE MAP; HERITABILITY; HUMAN; KCNJ16 GENE; METABOLOMICS; PHENOTYPE; PRODH GENE; PROTON NUCLEAR MAGNETIC RESONANCE; QUANTITATIVE TRAIT LOCUS MAPPING; SEQUENCE ANALYSIS; SERUM; SLC16A9 GENE; TNP1 GENE; BLOOD; FEMALE; GENETIC PREDISPOSITION; GENETICS; INBORN ERROR OF METABOLISM; METABOLOME; QUANTITATIVE TRAIT LOCUS; SINGLE NUCLEOTIDE POLYMORPHISM;

EXOME; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOME-WIDE ASSOCIATION STUDY; GLYCINE; HUMANS; METABOLISM, INBORN ERRORS; METABOLOME; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; PYRUVIC ACID; QUANTITATIVE TRAIT LOCI; VALINE;

EID: 84924402386     PISSN: 15537390     EISSN: 15537404     Source Type: Journal    
DOI: 10.1371/journal.pgen.1004835     Document Type: Article

References (75)

1. Chen G, Ramos E, Adeyemo A, Shriner D, Zhou J, et al. (2012) UGT1A1 is a major locus influencing bilirubin levels in African Americans. Eur J Hum Genet 20: 463–468.
2. McCarthy MI, Abecasis GR, Cardon LR, Goldstein DB, Little J, et al. (2008) Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nat Rev Genet 9: 356–369.
3. Danik JS, Pare G, Chasman DI, Zee RY, Kwiatkowski DJ, et al. (2009) Novel loci, including those related to Crohn disease, psoriasis, and inflammation, identified in a genome-wide association study of fibrinogen in 17 686 women: the Women's Genome Health Study. Circ Cardiovasc Genet 2: 134–141.
4. Chasman DI, Pare G, Mora S, Hopewell JC, Peloso G, et al. (2009) Forty-three loci associated with plasma lipoprotein size, concentration, and cholesterol content in genome-wide analysis. PLoS Genet 5: e1000730.
5. 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.
6. 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.
7. 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.
8. Xie W, Wood AR, Lyssenko V, Weedon MN, Knowles JW, et al. (2013) Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes. Diabetes.
9. 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.
10. Kottgen A, Albrecht E, Teumer A, Vitart V, Krumsiek J, et al. (2013) Genome-wide association analyses identify 18 new loci associated with serum urate concentrations. Nat Genet 45: 145–154.
11. Kolz M, Johnson T, Sanna S, Teumer A, Vitart V, et al. (2009) Meta-analysis of 28,141 individuals identifies common variants within five new loci that influence uric acid concentrations. PLoS Genet 5: e1000504.
12. Rueedi R LM, Nicholls AW., Reza M Salek, Pedro Marques-Vidal, Edgard Morya, Koichi Sameshima, Ivan Montoliu, Laeticia Da Silva, Sebastiano Collino, François-Pierre Martin, Serge Rezzi, Christoph Steinbeck, Dawn M Waterworth, Gérard Waeber, Peter Vollenweider, Jacques S Beckmann, Johannes Le Coutre, Vincent Mooser, Sven Bergmann, Ulrich K Genick, Zoltán Kutalik (2014) Genome-Wide Association Study of Metabolic Traits Reveals Novel Gene-Metabolite-Disease Links PLoS Genet.
13. Lappalainen T, Sammeth M, Friedlander MR, t Hoen PA, Monlong J, et al. (2013) Transcriptome and genome sequencing uncovers functional variation in humans. Nature 501: 506–511.
14. Mailman MD, Feolo M, Jin Y, Kimura M, Tryka K, et al. (2007) The NCBI dbGaP database of genotypes and phenotypes. Nat Genet 39: 1181–1186.
15. Ota VK, Bellucco FT, Gadelha A, Santoro ML, Noto C, et al. (2014) PRODH Polymorphisms, Cortical Volumes and Thickness in Schizophrenia. PLoS One 9: e87686.
16. Vorstman JA, Morcus ME, Duijff SN, Klaassen PW, Heineman-de Boer JA, et al. (2006) The 22q11.2 deletion in children: high rate of autistic disorders and early onset of psychotic symptoms. J Am Acad Child Adolesc Psychiatry 45: 1104–1113.
17. Fox CS, Liu Y, White CC, Feitosa M, Smith AV, et al. (2012) Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. PLoS Genet 8: e1002695.
18. Henneman P, Aulchenko YS, Frants RR, van Dijk KW, Oostra BA, et al. (2008) Prevalence and heritability of the metabolic syndrome and its individual components in a Dutch isolate: the Erasmus Rucphen Family study. J Med Genet 45: 572–577.
19. Aulchenko YS, Ripke S, Isaacs A, van Duijn CM, (2007) GenABEL: an R library for genome-wide association analysis. Bioinformatics 23: 1294–1296.
20. Abecasis GR, Cherny SS, Cookson WO, Cardon LR, (2002) Merlin—rapid analysis of dense genetic maps using sparse gene flow trees. Nat Genet 30: 97–101.
21. Amin N, van Duijn CM, Aulchenko YS, (2007) A genomic background based method for association analysis in related individuals. PLoS One 2: e1274.
22. Hindorff LA, Sethupathy P, Junkins HA, Ramos EM, Mehta JP, et al. (2009) Potential etiologic and functional implications of genome-wide association loci for human diseases and traits. Proc Natl Acad Sci USA 106: 9362–9367.
23. Sherry ST, Ward MH, Kholodov M, Baker J, Phan L, et al. (2001) dbSNP: the NCBI database of genetic variation. Nucleic Acids Res 29: 308–311.
24. Kamburov A, Pentchev K, Galicka H, Wierling C, Lehrach H, et al. (2011) ConsensusPathDB: toward a more complete picture of cell biology. Nucleic Acids Res 39: D712–D717.
25. Magrane M, UniProt Consortium (2011) UniProt Knowledgebase: a hub of integrated protein data. Database (Oxford) 2011.
26. McKusick VA (1998) Mendelian Inheritance in Man. A Catalog of Human Genes and Genetic Disorders. Baltimore: Johns Hopkins University Press.
27. Saier J, M.H., Tran CV, Barabote RD, (2006) TCDB: the Transporter Classification Database for membrane transport protein analyses and information. Nucleic Acids Res 34: D181–D186.
28. Gasteiger E, Gattiker A, Hoogland C, Ivanyi I, Appel RD, et al. (2003) ExPASy: The proteomics server for in-depth protein knowledge and analysis. Nucleic Acids Res 31: 3784–3788.
29. Kanehisa M, Goto S, (2000) KEGG: Kyoto Encyclopedia of Genes and Genomes. Nucleic Acids Research 28: 27–30.
30. Li H, Durbin R, (2009) Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 25: 1754–1760.
31. Brouwer RW, van den Hout MC, Grosveld FG, van Ijcken WF NARWHAL, a primary analysis pipeline for NGS data. Bioinformatics 28: 284–285.
32. 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.
33. Lange LA, Croteau-Chonka DC, Marvelle AF, Qin L, Gaulton KJ, et al. (2010) Genome-wide association study of homocysteine levels in Filipinos provides evidence for CPS1 in women and a stronger MTHFR effect in young adults. Hum Mol Genet 19: 2050–2058.
34. Xie W, Wood AR, Lyssenko V, Weedon MN, Knowles JW, et al. (2013) Genetic variants associated with glycine metabolism and their role in insulin sensitivity and type 2 diabetes. Diabetes 62: 2141–2150.
35. Hong MG, Karlsson R, Magnusson PK, Lewis MR, Isaacs W, et al. (2013) A genome-wide assessment of variability in human serum metabolism. Hum Mutat 34: 515–524.
36. 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.
37. Lee Y, Yoon KA, Joo J, Lee D, Bae K, et al. (2013) Prognostic implications of genetic variants in advanced non-small cell lung cancer: a genome-wide association study. Carcinogenesis 34: 307–313.
38. Inouye M, Ripatti S, Kettunen J, Lyytikainen LP, Oksala N, et al. (2012) Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. PLoS Genet 8: e1002907.
39. Sanna S, Jackson AU, Nagaraja R, Willer CJ, Chen WM, et al. (2008) Common variants in the GDF5-UQCC region are associated with variation in human height. Nat Genet 40: 198–203.
40. Rietschel M, Mattheisen M, Frank J, Treutlein J, Degenhardt F, et al. (2010) Genome-wide association-, replication-, and neuroimaging study implicates HOMER1 in the etiology of major depression. Biol Psychiatry 68: 578–585.
41. Benyamin B, McRae AF, Zhu G, Gordon S, Henders AK, et al. (2009) Variants in TF and HFE explain approximately 40% of genetic variation in serum-transferrin levels. Am J Hum Genet 84: 60–65.
42. Potkin SG, Guffanti G, Lakatos A, Turner JA, Kruggel F, et al. (2009) Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer's disease. PLoS One 4: e6501.
43. Benjamin DJ, Cesarini D, van der Loos MJ, Dawes CT, Koellinger PD, et al. (2012) The genetic architecture of economic and political preferences. Proc Natl Acad Sci U S A 109: 8026–8031.
44. Wu JH, Lemaitre RN, Manichaikul A, Guan W, Tanaka T, et al. (2013) Genome-wide association study identifies novel loci associated with concentrations of four plasma phospholipid fatty acids in the de novo lipogenesis pathway: results from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Circ Cardiovasc Genet 6: 171–183.
45. Porcu E, Medici M, Pistis G, Volpato CB, Wilson SG, et al. (2013) A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function. PLoS Genet 9: e1003266.
46. Geller F, Feenstra B, Zhang H, Shaffer JR, Hansen T, et al. (2011) Genome-wide association study identifies four loci associated with eruption of permanent teeth. PLoS Genet 7: e1002275.
47. Michailidou K, Hall P, Gonzalez-Neira A, Ghoussaini M, Dennis J, et al. (2013) Large-scale genotyping identifies 41 new loci associated with breast cancer risk. Nat Genet 45: 353-361, 361e351–352.
48. Fletcher O, Johnson N, Orr N, Hosking FJ, Gibson LJ, et al. (2011) Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide association study. J Natl Cancer Inst 103: 425–435.
49. Li J, Humphreys K, Heikkinen T, Aittomaki K, Blomqvist C, et al. (2011) A combined analysis of genome-wide association studies in breast cancer. Breast Cancer Res Treat 126: 717–727.
50. Thomas G, Jacobs KB, Kraft P, Yeager M, Wacholder S, et al. (2009) A multistage genome-wide association study in breast cancer identifies two new risk alleles at 1p11.2 and 14q24.1 (RAD51L1). Nat Genet 41: 579–584.
51. Stacey SN, Manolescu A, Sulem P, Rafnar T, Gudmundsson J, et al. (2007) Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor-positive breast cancer. Nat Genet 39: 865–869.
52. N'Diaye A, Chen GK, Palmer CD, Ge B, Tayo B, et al. (2011) Identification, replication, and fine-mapping of Loci associated with adult height in individuals of african ancestry. PLoS Genet 7: e1002298.
53. Lango Allen H, Estrada K, Lettre G, Berndt SI, Weedon MN, et al. (2010) Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature 467: 832–838.
54. Pillas D, Hoggart CJ, Evans DM, O'Reilly PF, Sipila K, et al. (2010) Genome-wide association study reveals multiple loci associated with primary tooth development during infancy. PLoS Genet 6: e1000856.
55. Jongjaroenprasert W, Phusantisampan T, Mahasirimongkol S, Mushiroda T, Hirankarn N, et al. (2012) A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis. J Hum Genet 57: 301–304.
56. Cheung CL, Lau KS, Ho AY, Lee KK, Tiu SC, et al. (2012) Genome-wide association study identifies a susceptibility locus for thyrotoxic periodic paralysis at 17q24.3. Nat Genet 44: 1026–1029.
57. Rothenberg ME, Spergel JM, Sherrill JD, Annaiah K, Martin LJ, et al. (2010) Common variants at 5q22 associate with pediatric eosinophilic esophagitis. Nat Genet 42: 289–291.
58. Krintel SB, Palermo G, Johansen JS, Germer S, Essioux L, et al. (2012) Investigation of single nucleotide polymorphisms and biological pathways associated with response to TNFalpha inhibitors in patients with rheumatoid arthritis. Pharmacogenet Genomics 22: 577–589.
59. Pfeufer A, Sanna S, Arking DE, Muller M, Gateva V, et al. (2009) Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nat Genet 41: 407–414.
60. Marjamaa A, Oikarinen L, Porthan K, Ripatti S, Peloso G, et al. (2012) A common variant near the KCNJ2 gene is associated with T-peak to T-end interval. Heart Rhythm 9: 1099–1103.
61. Comuzzie AG, Cole SA, Laston SL, Voruganti VS, Haack K, et al. (2012) Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. PLoS One 7: e51954.
62. Meyer TE, Verwoert GC, Hwang SJ, Glazer NL, Smith AV, et al. (2010) Genome-wide association studies of serum magnesium, potassium, and sodium concentrations identify six Loci influencing serum magnesium levels. PLoS Genet 6.
63. Sabatti C, (2009) Service SK, Hartikainen AL, Pouta A, Ripatti S, et al (2009) Genome-wide association analysis of metabolic traits in a birth cohort from a founder population. Nat Genet 41: 35–46.
64. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, et al. (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466: 707–713.
65. Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, et al. (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 40: 161–169.
66. Aulchenko YS, Ripatti S, Lindqvist I, Boomsma D, Heid IM, et al. (2009) Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. Nat Genet 41: 47–55.
67. Kathiresan S, Willer CJ, Peloso GM, Demissie S, Musunuru K, et al. (2009) Common variants at 30 loci contribute to polygenic dyslipidemia. Nat Genet 41: 56–65.
68. Consortium UIG, Barrett JC, Lee JC, Lees CW, Prescott NJ, et al. (2009) Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A region. Nat Genet 41: 1330–1334.
69. Anderson CA, Boucher G, Lees CW, Franke A, D'Amato M, et al. (2011) Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43: 246–252.
70. Lingappa JR, Petrovski S, Kahle E, Fellay J, Shianna K, et al. (2011) Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure. PLoS One 6: e28632.
71. McClay JL, Adkins DE, Aberg K, Bukszar J, Khachane AN, et al. (2011) Genome-wide pharmacogenomic study of neurocognition as an indicator of antipsychotic treatment response in schizophrenia. Neuropsychopharmacology 36: 616–626.
72. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, et al. (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491: 119–124.
73. Kenny EE, Pe'er I, Karban A, Ozelius L, Mitchell AA, et al. (2012) A genome-wide scan of Ashkenazi Jewish Crohn's disease suggests novel susceptibility loci. PLoS Genet 8: e1002559.
74. Kristiansson K, Perola M, Tikkanen E, Kettunen J, Surakka I, et al. (2012) Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits. Circ Cardiovasc Genet 5: 242–249.
75. Lettre G, Palmer CD, Young T, Ejebe KG, Allayee H, et al. (2011) Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. PLoS Genet 7: e1001300.