Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

American Journal of Human Genetics

Volumn 99, Issue 1, 2016, Pages 56-75

  Liu, Ching Ti ^a   Raghavan, Sridharan ^b,c,d   Maruthur, Nisa ^e,f,g   Kabagambe, Edmond Kato ^h   Hong, Jaeyoung ^a   Ng, Maggie C Y ⁱ   Hivert, Marie France ^b,j,k   Lu, Yingchang ^l   An, Ping ^m   Bentley, Amy R ⁿ   Drolet, Anne M ^o   Gaulton, Kyle J ^p   Guo, Xiuqing ^q   Armstrong, Loren L ^r   Irvin, Marguerite R ^s   Li, Man ^g   Lipovich, Leonard ^o   Rybin, Denis V ^a   Taylor, Kent D ^q   Agyemang, Charles ^t   Palmer, Nicholette D ⁱ   Cade, Brian E ^u   Chen, Wei Min ^v   Dauriz, Marco ^w   Delaney, Joseph A C ^x   Edwards, Todd L ^h   Evans, Daniel S ^y   Evans, Michele K ^z   Lange, Leslie A ^aa   Leong, Aaron ^b   Liu, Jingmin ^ab   Liu, Yongmei ⁱ   Nayak, Uma ^v   Patel, Sanjay R ^ac   Porneala, Bianca C ^b   Rasmussen Torvik, Laura J ^r   Snijder, Marieke B ^t   Stallings, Sarah C ^h   Tanaka, Toshiko ^z   Yanek, Lisa R ^e   Zhao, Wei ^ad   Becker, Diane M ^e,g   Bielak, Lawrence F ^ad   Biggs, Mary L ^x,ae   Bottinger, Erwin P ^l   Bowden, Donald W ⁱ   Chen, Guanjie ⁿ   Correa, Adolfo ^af   Couper, David J ^ag   Crawford, Dana C ^ah   Cushman, Mary ^ai   Eicher, John D ^aj,ak   Fornage, Myriam ^al   Franceschini, Nora ^ag   Fu, Yi Ping ^ak   Goodarzi, Mark O ^am   Gottesman, Omri ^l   Hara, Kazuo ^l,an,ao   Harris, Tamara B ^ap   Jensen, Richard A ^ae   Johnson, Andrew D ^ak   Jhun, Min A ^ad   Karter, Andrew J ^aq   Keller, Margaux F ^ar   Kho, Abel N ^r   Kizer, Jorge R ^as   Krauss, Ronald M ^at   Langefeld, Carl D ⁱ   Li, Xiaohui ^q   Liang, Jingling ^ah   Liu, Simin ^au,av   Lowe, William L ^r   Mosley, Thomas H ^af   North, Kari E ^ag   Pacheco, Jennifer A ^r   Peyser, Patricia A ^ad   Patrick, Alan L ^aw   Rice, Kenneth M ^x   Selvin, Elizabeth ^f,g   Sims, Mario ^af   Smith, Jennifer A ^ad   Tajuddin, Salman M ^z   Vaidya, Dhananjay ^e,g   Wren, Mary P ⁱ   Yao, Jie ^q   Zhu, Xiaofeng ^ah   Ziegler, Julie T ⁱ   Zmuda, Joseph M ^ax   Zonderman, Alan B ^z   Zwinderman, Aeilko H ^t   Adeyemo, Adebowale ⁿ   Boerwinkle, Eric ^al   Ferrucci, Luigi ^z   Hayes, M Geoffrey ^r   Kardia, Sharon L R ^ad   Miljkovic, Iva ^ax   Pankow, James S ^ay   Rotimi, Charles N ⁿ   Sale, Michele M ^v   Wagenknecht, Lynne E ⁱ   Arnett, Donna K ^az   Chen, Yii Der Ida ^q   Nalls, Michael A ^z   Province, Michael A ^m   Kao, W H Linda ^g   Siscovick, David S ^x,ae,ba   Psaty, Bruce M ^x,ae,bb   Wilson, James G ^af   Loos, Ruth J F ^l   Dupuis, Josée ^a,aj   Rich, Stephen S ^v   Florez, Jose C ^b,j,bc   Rotter, Jerome I ^q   Morris, Andrew P ^p,bd   Meigs, James B ^b   more..

^a BOSTON UNIVERSITY   (United States)

^b MASSACHUSETTS GENERAL HOSPITAL   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

^d UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^e JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^f JOHNS HOPKINS UNIVERSITY   (United States)

^g JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

^h VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

ⁱ WAKE FOREST SCHOOL OF MEDICINE   (United States)

^j HARVARD MEDICAL SCHOOL   (United States)

^k UNIVERSITÉ DE SHERBROOKE   (Canada)

^l MOUNT SINAI SCHOOL OF MEDICINE   (United States)

^m WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

ⁿ NATIONAL HUMAN GENOME RESEARCH INSTITUTE   (United States)

^o WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^p UNIVERSITY OF OXFORD   (United Kingdom)

^q HARBOR UCLA MEDICAL CENTER   (United States)

^r NORTHWESTERN UNIVERSITY   (United States)

^s UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

^t ACADEMIC MEDICAL CENTER   (Netherlands)

^u BRIGHAM AND WOMEN S HOSPITAL   (United States)

^v UNIVERSITY OF VIRGINIA   (United States)

^w UNIVERSITY OF VERONA   (Italy)

^x UNIVERSITY OF WASHINGTON   (United States)

^y CALIFORNIA PACIFIC MEDICAL CENTER   (United States)

^z NATIONAL INSTITUTE ON AGING   (United States)

^aa UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

^ab Fred Hutchinson Cancer Research Center   (United States)

^ac UNIVERSITY OF PITTSBURGH SCHOOL OF MEDICINE   (United States)

^ad UNIVERSITY OF MICHIGAN   (United States)

^ae UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE   (United States)

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

^ag IL   (United States)

^ah CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^ai UNIVERSITY OF VERMONT COLLEGE OF MEDICINE   (United States)

^aj FRAMINGHAM HEART STUDY   (United States)

^ak NATIONAL HEART LUNG AND BLOOD INSTITUTE   (United States)

^al UNIVERSITY OF TEXAS MEDICAL SCHOOL   (United States)

^am CEDARS SINAI MEDICAL CENTER   (United States)

^an UNIVERSITY OF TOKYO   (Japan)

^ao TOKYO MEDICAL UNIVERSITY   (Japan)

^ap NATIONAL INSTITUTES OF HEALTH   (United States)

^aq DIVISION OF RESEARCH   (United States)

^ar MERCK RESEARCH LABORATORIES   (United States)

^as ALBERT EINSTEIN COLLEGE OF MEDICINE   (United States)

^at CHILDREN S HOSPITAL OAKLAND RESEARCH INSTITUTE   (United States)

^au BROWN UNIVERSITY   (United States)

^av BROWN UNIVERSITY   (United States)

^aw Tobago Health Studies Office   (Trinidad and Tobago)

^ax UNIVERSITY OF PITTSBURGH GRADUATE SCHOOL OF PUBLIC HEALTH   (United States)

^ay UNIVERSITY OF MINNESOTA   (United States)

^az UNIVERSITY OF KENTUCKY COLLEGE OF PUBLIC HEALTH   (United States)

^ba NEW YORK ACADEMY OF MEDICINE   (United States)

^bb CENTER FOR HEALTH STUDIES   (United States)

^bc BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^bd UNIVERSITY OF LIVERPOOL   (United Kingdom)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ACYL COENZYME A DESATURASE 1; ALPHA 2A ADRENERGIC RECEPTOR; CRYPTOCHROME 2; CYCLIN DEPENDENT KINASE INHIBITOR 2B; GLUCOSE; HEPATOCYTE NUCLEAR FACTOR 3BETA; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INSULIN; LOW DENSITY LIPOPROTEIN CHOLESTEROL; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; PROTEIN; PROTEIN ADCY5; PROTEIN ANKRD55; PROTEIN ARL15; PROTEIN DGKB; PROTEIN DPYSL5; PROTEIN FAM13A; PROTEIN GCK; PROTEIN GCKR; PROTEIN IGF2BP2; PROTEIN IRS1; PROTEIN KL; PROTEIN PPP1R3B; PROTEIN PROX1; PROTEIN UHRF1BP1; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR 7 LIKE 2; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; GLUCOSE BLOOD LEVEL;

ARTICLE; BINDING SITE; DIET RESTRICTION; ENHANCER REGION; EUROPEAN; GENE CONTROL; GENE FREQUENCY; GENE LOCUS; GENE MAPPING; GENETIC ASSOCIATION; GENETIC VARIABILITY; HUMAN; INSULIN RESISTANCE; META ANALYSIS; NON INSULIN DEPENDENT DIABETES MELLITUS; PRIORITY JOURNAL; QUANTITATIVE TRAIT LOCUS; SINGLE NUCLEOTIDE POLYMORPHISM; ANCESTRY GROUP; ASIAN CONTINENTAL ANCESTRY GROUP; BLACK PERSON; CAUCASIAN; ETHNIC GROUP; FEMALE; GENETICS; GENOME-WIDE ASSOCIATION STUDY; GLUCOSE BLOOD LEVEL; INTRON; MALE; METABOLISM; MOLECULAR GENETICS; PANCREAS ISLET;

AFRICAN CONTINENTAL ANCESTRY GROUP; ASIAN CONTINENTAL ANCESTRY GROUP; BLOOD GLUCOSE; CONTINENTAL POPULATION GROUPS; DIABETES MELLITUS, TYPE 2; ENHANCER ELEMENTS, GENETIC; ETHNIC GROUPS; EUROPEAN CONTINENTAL ANCESTRY GROUP; FASTING; FEMALE; GENE FREQUENCY; GENOME-WIDE ASSOCIATION STUDY; HUMANS; INSULIN; INSULIN RESISTANCE; INTRONS; ISLETS OF LANGERHANS; MALE; MOLECULAR SEQUENCE ANNOTATION; POLYMORPHISM, SINGLE NUCLEOTIDE; QUANTITATIVE TRAIT LOCI; TRANSCRIPTION FACTORS;

EID: 84989888965     PISSN: 00029297     EISSN: 15376605     Source Type: Journal    
DOI: 10.1016/j.ajhg.2016.05.006     Document Type: Article

References (61)

1. 1 Danaei, G., Finucane, M.M., Lu, Y., Singh, G.M., Cowan, M.J., Paciorek, C.J., Lin, J.K., Farzadfar, F., Khang, Y.H., Stevens, G.A., et al., Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group (Blood Glucose). National, regional, and global trends in fasting plasma glucose and diabetes prevalence since 1980: systematic analysis of health examination surveys and epidemiological studies with 370 country-years and 2·7 million participants. Lancet 378 (2011), 31–40.
2. 2 Spanakis, E.K., Golden, S.H., Race/ethnic difference in diabetes and diabetic complications. Curr. Diab. Rep. 13 (2013), 814–823.
3. 3 Cheng, C.Y., Reich, D., Haiman, C.A., Tandon, A., Patterson, N., Selvin, E., Akylbekova, E.L., Brancati, F.L., Coresh, J., Boerwinkle, E., et al. African ancestry and its correlation to type 2 diabetes in African Americans: a genetic admixture analysis in three U.S. population cohorts. PLoS ONE, 7, 2012, e32840.
4. 4 Rosenberg, N.A., Huang, L., Jewett, E.M., Szpiech, Z.A., Jankovic, I., Boehnke, M., Genome-wide association studies in diverse populations. Nat. Rev. Genet. 11 (2010), 356–366.
5. 5 Fesinmeyer, M.D., Meigs, J.B., North, K.E., Schumacher, F.R., Bůžková, P., Franceschini, N., Haessler, J., Goodloe, R., Spencer, K.L., Voruganti, V.S., et al. Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study. BMC Med. Genet., 14, 2013, 98.
6. 6 Rasmussen-Torvik, L.J., Guo, X., Bowden, D.W., Bertoni, A.G., Sale, M.M., Yao, J., Bluemke, D.A., Goodarzi, M.O., Chen, Y.I., Vaidya, D., et al. Fasting glucose GWAS candidate region analysis across ethnic groups in the Multiethnic Study of Atherosclerosis (MESA). Genet. Epidemiol. 36 (2012), 384–391.
7. 7 Liu, C.T., Ng, M.C., Rybin, D., Adeyemo, A., Bielinski, S.J., Boerwinkle, E., Borecki, I., Cade, B., Chen, Y.D., Djousse, L., et al. Transferability and fine-mapping of glucose and insulin quantitative trait loci across populations: CARe, the Candidate Gene Association Resource. Diabetologia 55 (2012), 2970–2984.
8. 8 Scott, R.A., Lagou, V., Welch, R.P., Wheeler, E., Montasser, M.E., Luan, J., Mägi, R., Strawbridge, R.J., Rehnberg, E., Gustafsson, S., et al., DIAbetes Genetics Replication and Meta-analysis (DIAGRAM) Consortium. Large-scale association analyses identify new loci influencing glycemic traits and provide insight into the underlying biological pathways. Nat. Genet. 44 (2012), 991–1005.
9. 9 Dupuis, J., Langenberg, C., Prokopenko, I., Saxena, R., Soranzo, N., Jackson, A.U., Wheeler, E., Glazer, N.L., Bouatia-Naji, N., Gloyn, A.L., et al. DIAGRAM Consortium GIANT Consortium Global BPgen Consortium Anders Hamsten on behalf of Procardis Consortium, MAGIC investigators. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat. Genet. 42 (2010), 105–116.
10. 10 Manning, A.K., Hivert, M.F., Scott, R.A., Grimsby, J.L., Bouatia-Naji, N., Chen, H., Rybin, D., Liu, C.T., Bielak, L.F., Prokopenko, I., et al. DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Multiple Tissue Human Expression Resource (MUTHER) Consortium. A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance. Nat. Genet. 44 (2012), 659–669.
11. 11 Boyle, A.P., Hong, E.L., Hariharan, M., Cheng, Y., Schaub, M.A., Kasowski, M., Karczewski, K.J., Park, J., Hitz, B.C., Weng, S., et al. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 22 (2012), 1790–1797.
12. 12 Ward, L.D., Kellis, M., HaploReg: a resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants. Nucleic Acids Res. 40 (2012), D930–D934.
13. 13 Pasquali, L., Gaulton, K.J., Rodríguez-Seguí, S.A., Mularoni, L., Miguel-Escalada, I., Akerman, I., Tena, J.J., Morán, I., Gómez-Marín, C., van de Bunt, M., et al. Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants. Nat. Genet. 46 (2014), 136–143.
14. 14 Lizio, M., Harshbarger, J., Shimoji, H., Severin, J., Kasukawa, T., Sahin, S., Abugessaisa, I., Fukuda, S., Hori, F., Ishikawa-Kato, S., et al., FANTOM consortium. Gateways to the FANTOM5 promoter level mammalian expression atlas. Genome Biol., 16, 2015, 22.
15. 15 Morris, A.P., Transethnic meta-analysis of genomewide association studies. Genet. Epidemiol. 35 (2011), 809–822.
16. 16 Mahajan, A., Go, M.J., Zhang, W., Below, J.E., Gaulton, K.J., Ferreira, T., Horikoshi, M., Johnson, A.D., Ng, M.C., Prokopenko, I., et al. DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium South Asian Type 2 Diabetes (SAT2D) Consortium Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility. Nat. Genet. 46 (2014), 234–244.
17. 17 Devlin, B., Roeder, K., Genomic control for association studies. Biometrics 55 (1999), 997–1004.
18. 18 Howie, B., Fuchsberger, C., Stephens, M., Marchini, J., Abecasis, G.R., Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat. Genet. 44 (2012), 955–959.
19. 19 Willer, C.J., Li, Y., Abecasis, G.R., METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26 (2010), 2190–2191.
20. 20 Hong, J., Lunetta, K.L., Cupples, L.A., Dupuis, J., Liu, C.T., Evaluation of a two-stage approach in trans-ethnic meta-analysis in genome-wide association studies. Genet. Epidemiol. 40 (2016), 284–292.
21. 21 Maller, J.B., McVean, G., Byrnes, J., Vukcevic, D., Palin, K., Su, Z., Howson, J.M., Auton, A., Myers, S., Morris, A., et al., Wellcome Trust Case Control Consortium. Bayesian refinement of association signals for 14 loci in 3 common diseases. Nat. Genet. 44 (2012), 1294–1301.
22. 22 Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., Ziller, M.J., et al., Roadmap Epigenomics Consortium. Integrative analysis of 111 reference human epigenomes. Nature 518 (2015), 317–330.
23. 23 Bernstein, B.E., Birney, E., Dunham, I., Green, E.D., Gunter, C., Snyder, M., Consortium, E.P., ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature 489 (2012), 57–74.
24. 24 Li, J., Ji, L., Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity (Edinb) 95 (2005), 221–227.
25. 25 Yang, J., Ferreira, T., Morris, A.P., Medland, S.E., Madden, P.A., Heath, A.C., Martin, N.G., Montgomery, G.W., Weedon, M.N., Loos, R.J., et al. Genetic Investigation of ANthropometric Traits (GIANT) Consortium, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits. Nat. Genet. 44 (2012), 369–375, S1–S3.
26. 26 Wright, S., The interpretation of population structure by F-statistics with special regard to systems of mating. Evolution 19 (1965), 395–420.
27. 27 Wright, S., Evolution and the Genetics of Population, Variability Within and Among Natural Populations. 1978, University of Chicago Press.
28. 28 Balloux, F., Lugon-Moulin, N., The estimation of population differentiation with microsatellite markers. Mol. Ecol. 11 (2002), 155–165.
29. 29 Voight, B.F., Kudaravalli, S., Wen, X., Pritchard, J.K., A map of recent positive selection in the human genome. PLoS Biol., 4, 2006, e72.
30. 30 Kent, W.J., Sugnet, C.W., Furey, T.S., Roskin, K.M., Pringle, T.H., Zahler, A.M., Haussler, D., The human genome browser at UCSC. Genome Res. 12 (2002), 996–1006.
31. 31 Ng, M.C., Shriner, D., Chen, B.H., Li, J., Chen, W.M., Guo, X., Liu, J., Bielinski, S.J., Yanek, L.R., Nalls, M.A., et al. FIND Consortium eMERGE Consortium DIAGRAM Consortium MuTHER Consortium, MEta-analysis of type 2 DIabetes in African Americans Consortium. Meta-analysis of genome-wide association studies in African Americans provides insights into the genetic architecture of type 2 diabetes. PLoS Genet., 10, 2014, e1004517.
32. 32 Monda, K.L., Chen, G.K., Taylor, K.C., Palmer, C., Edwards, T.L., Lange, L.A., Ng, M.C., Adeyemo, A.A., Allison, M.A., Bielak, L.F., et al. NABEC Consortium UKBEC Consortium BioBank Japan Project, AGEN Consortium. A meta-analysis identifies new loci associated with body mass index in individuals of African ancestry. Nat. Genet. 45 (2013), 690–696.
33. 33 Liu, C.T., Monda, K.L., Taylor, K.C., Lange, L., Demerath, E.W., Palmas, W., Wojczynski, M.K., Ellis, J.C., Vitolins, M.Z., Liu, S., et al. Genome-wide association of body fat distribution in African ancestry populations suggests new loci. PLoS Genet., 9, 2013, e1003681.
34. 34 Franceschini, N., Fox, E., Zhang, Z., Edwards, T.L., Nalls, M.A., Sung, Y.J., Tayo, B.O., Sun, Y.V., Gottesman, O., Adeyemo, A., et al., Asian Genetic Epidemiology Network Consortium. Genome-wide association analysis of blood-pressure traits in African-ancestry individuals reveals common associated genes in African and non-African populations. Am. J. Hum. Genet. 93 (2013), 545–554.
35. 35 Lettre, G., Palmer, C.D., Young, T., Ejebe, K.G., Allayee, H., Benjamin, E.J., Bennett, F., Bowden, D.W., Chakravarti, A., Dreisbach, A., et al. Genome-wide association study of coronary heart disease and its risk factors in 8,090 African Americans: the NHLBI CARe Project. PLoS Genet., 7, 2011, e1001300.
36. 36 McCarty, C.A., Chisholm, R.L., Chute, C.G., Kullo, I.J., Jarvik, G.P., Larson, E.B., Li, R., Masys, D.R., Ritchie, M.D., Roden, D.M., et al., eMERGE Team. The eMERGE Network: a consortium of biorepositories linked to electronic medical records data for conducting genomic studies. BMC Med. Genomics, 4, 2011, 13.
37. 37 Gouda, H.N., Sagoo, G.S., Harding, A.H., Yates, J., Sandhu, M.S., Higgins, J.P., The association between the peroxisome proliferator-activated receptor-gamma2 (PPARG2) Pro12Ala gene variant and type 2 diabetes mellitus: a HuGE review and meta-analysis. Am. J. Epidemiol. 171 (2010), 645–655.
38. 38 Gaulton, K.J., Nammo, T., Pasquali, L., Simon, J.M., Giresi, P.G., Fogarty, M.P., Panhuis, T.M., Mieczkowski, P., Secchi, A., Bosco, D., et al. A map of open chromatin in human pancreatic islets. Nat. Genet. 42 (2010), 255–259.
39. 39 Orho-Melander, M., Melander, O., Guiducci, C., Perez-Martinez, P., Corella, D., Roos, C., Tewhey, R., Rieder, M.J., Hall, J., Abecasis, G., et al. Common missense variant in the glucokinase regulatory protein gene is associated with increased plasma triglyceride and C-reactive protein but lower fasting glucose concentrations. Diabetes 57 (2008), 3112–3121.
40. 40 Beer, N.L., Tribble, N.D., McCulloch, L.J., Roos, C., Johnson, P.R., Orho-Melander, M., Gloyn, A.L., The P446L variant in GCKR associated with fasting plasma glucose and triglyceride levels exerts its effect through increased glucokinase activity in liver. Hum. Mol. Genet. 18 (2009), 4081–4088.
41. 41 Jiang, W., Liu, Y., Liu, R., Zhang, K., Zhang, Y., The lncRNA DEANR1 facilitates human endoderm differentiation by activating FOXA2 expression. Cell Rep. 11 (2015), 137–148.
42. 42 Ng, M.C., Saxena, R., Li, J., Palmer, N.D., Dimitrov, L., Xu, J., Rasmussen-Torvik, L.J., Zmuda, J.M., Siscovick, D.S., Patel, S.R., et al. Transferability and fine mapping of type 2 diabetes loci in African Americans: the Candidate Gene Association Resource Plus Study. Diabetes 62 (2013), 965–976.
43. 43 Schaub, M.A., Boyle, A.P., Kundaje, A., Batzoglou, S., Snyder, M., Linking disease associations with regulatory information in the human genome. Genome Res. 22 (2012), 1748–1759.
44. 44 Maurano, M.T., Humbert, R., Rynes, E., Thurman, R.E., Haugen, E., Wang, H., Reynolds, A.P., Sandstrom, R., Qu, H., Brody, J., et al. Systematic localization of common disease-associated variation in regulatory DNA. Science 337 (2012), 1190–1195.
45. 45 Claussnitzer, M., Dankel, S.N., Klocke, B., Grallert, H., Glunk, V., Berulava, T., Lee, H., Oskolkov, N., Fadista, J., Ehlers, K., et al., DIAGRAM+Consortium. Leveraging cross-species transcription factor binding site patterns: from diabetes risk loci to disease mechanisms. Cell 156 (2014), 343–358.
46. 46 Matthews, D.R., Hosker, J.P., Rudenski, A.S., Naylor, B.A., Treacher, D.F., Turner, R.C., Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28 (1985), 412–419.
47. 47 Laakso, M., How good a marker is insulin level for insulin resistance?. Am. J. Epidemiol. 137 (1993), 959–965.
48. 48 Kahn, S.E., Prigeon, R.L., McCulloch, D.K., Boyko, E.J., Bergman, R.N., Schwartz, M.W., Neifing, J.L., Ward, W.K., Beard, J.C., Palmer, J.P., et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 42 (1993), 1663–1672.
49. 49 Weyer, C., Hanson, R.L., Tataranni, P.A., Bogardus, C., Pratley, R.E., A high fasting plasma insulin concentration predicts type 2 diabetes independent of insulin resistance: evidence for a pathogenic role of relative hyperinsulinemia. Diabetes 49 (2000), 2094–2101.
50. 50 Ferrannini, E., Natali, A., Bell, P., Cavallo-Perin, P., Lalic, N., Mingrone, G., European Group for the Study of Insulin Resistance (EGIR). Insulin resistance and hypersecretion in obesity. J. Clin. Invest. 100 (1997), 1166–1173.
51. 51 Corkey, B.E., Banting lecture 2011: hyperinsulinemia: cause or consequence?. Diabetes 61 (2012), 4–13.
52. 52 Corkey, B.E., Diabetes: have we got it all wrong? Insulin hypersecretion and food additives: cause of obesity and diabetes?. Diabetes Care 35 (2012), 2432–2437.
53. 53 Chen, C.H., Cruz, L.A., Mochly-Rosen, D., Pharmacological recruitment of aldehyde dehydrogenase 3A1 (ALDH3A1) to assist ALDH2 in acetaldehyde and ethanol metabolism in vivo. Proc. Natl. Acad. Sci. USA 112 (2015), 3074–3079.
54. 54 Doudna, J.A., Charpentier, E., Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science, 346, 2014, 1258096.
55. 55 Pautsch, A., Stadler, N., Löhle, A., Rist, W., Berg, A., Glocker, L., Nar, H., Reinert, D., Lenter, M., Heckel, A., et al. Crystal structure of glucokinase regulatory protein. Biochemistry 52 (2013), 3523–3531.
56. 56 Saxena, R., Voight, B.F., Lyssenko, V., Burtt, N.P., de Bakker, P.I., Chen, H., Roix, J.J., Kathiresan, S., Hirschhorn, J.N., Daly, M.J., et al., Diabetes Genetics Initiative of Broad Institute of Harvard and MIT, Lund University, and Novartis Institutes of BioMedical Research. Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels. Science 316 (2007), 1331–1336.
57. 57 Vaxillaire, M., Cavalcanti-Proença, C., Dechaume, A., Tichet, J., Marre, M., Balkau, B., Froguel, P., DESIR Study Group. The common P446L polymorphism in GCKR inversely modulates fasting glucose and triglyceride levels and reduces type 2 diabetes risk in the DESIR prospective general French population. Diabetes 57 (2008), 2253–2257.
58. 58 Udler, M.S., Ahmed, S., Healey, C.S., Meyer, K., Struewing, J., Maranian, M., Kwon, E.M., Zhang, J., Tyrer, J., Karlins, E., et al. Fine scale mapping of the breast cancer 16q12 locus. Hum. Mol. Genet. 19 (2010), 2507–2515.
59. 59 Franceschini, N., van Rooij, F.J., Prins, B.P., Feitosa, M.F., Karakas, M., Eckfeldt, J.H., Folsom, A.R., Kopp, J., Vaez, A., Andrews, J.S., et al., LifeLines Cohort Study. Discovery and fine mapping of serum protein loci through transethnic meta-analysis. Am. J. Hum. Genet. 91 (2012), 744–753.
60. 60 Liu, C.T., Buchkovich, M.L., Winkler, T.W., Heid, I.M., Borecki, I.B., Fox, C.S., Mohlke, K.L., North, K.E., Adrienne Cupples, L., Consortium, A.A.A.G., et al. African Ancestry Anthropometry Genetics Consortium, GIANT Consortium. Multi-ethnic fine-mapping of 14 central adiposity loci. Hum. Mol. Genet. 23 (2014), 4738–4744.
61. 61 Ong, R.T., Teo, Y.Y., varLD: a program for quantifying variation in linkage disequilibrium patterns between populations. Bioinformatics 26 (2010), 1269–1270.