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Volumn 75, Issue 2-4, 2013, Pages 90-97

Epigenetics and obesity: A relationship waiting to be explained

Author keywords

Epigenome wide association studies; Methylation; Obesity; Tissue differentiation

Indexed keywords

ARTICLE; ENERGY EXPENDITURE; EPIGENETICS; GENE LOCUS; GENOME ANALYSIS; MOLECULAR MECHANICS; OBESITY; RISK FACTOR; SINGLE NUCLEOTIDE POLYMORPHISM; ADIPOSE TISSUE; BEIGE ADIPOSE TISSUE; BIRTH WEIGHT; BODY COMPOSITION; BROWN ADIPOSE TISSUE; DNA METHYLATION; DNA MODIFICATION; EMBRYO TRANSFER; FAT MASS; GENETIC ASSOCIATION; GENETIC RISK; GENETIC VARIABILITY; GLUCOSE HOMEOSTASIS; HUMAN; INTRAUTERINE GROWTH RETARDATION; LIPID STORAGE; MACRONUTRIENT; MATERNAL AGE; MATERNAL OBESITY; NONHUMAN; NONSHIVERING THERMOGENESIS; PLACENTA FUNCTION; PRENATAL EXPOSURE; RODENT MODEL; SPECIES; WHITE ADIPOSE TISSUE;

EID: 84884998962     PISSN: 00015652     EISSN: 14230062     Source Type: Journal    
DOI: 10.1159/000352009     Document Type: Article
Times cited : (22)

References (92)
  • 6
    • 84874645213 scopus 로고    scopus 로고
    • Beyond the fourth wave of genome-wide obesity association studies
    • Sandholt CH, Hansen T, Pedersen O: Beyond the fourth wave of genome-wide obesity association studies. Nutr Diabetes 2012; 2:e37.
    • (2012) Nutr Diabetes , vol.2
    • Sandholt, C.H.1    Hansen, T.2    Pedersen, O.3
  • 7
    • 78049446063 scopus 로고    scopus 로고
    • Chipping away the 'missing heritability': Giant steps forward in the molecular elucidation of obesity - But still lots to go
    • Hebebrand J, Volckmar AL, Knoll N, Hinney A: Chipping away the 'missing heritability': giant steps forward in the molecular elucidation of obesity - but still lots to go. Obes Facts 2010; 3: 294-303.
    • (2010) Obes Facts , vol.3 , pp. 294-303
    • Hebebrand, J.1    Volckmar, A.L.2    Knoll, N.3    Hinney, A.4
  • 9
    • 79952384705 scopus 로고    scopus 로고
    • Cancer epigenetics reaches mainstream oncology
    • Rodriguez-Paredes M, Esteller M: Cancer epigenetics reaches mainstream oncology. Nat Med 2011; 17: 330-339.
    • (2011) Nat Med , vol.17 , pp. 330-339
    • Rodriguez-Paredes, M.1    Esteller, M.2
  • 10
    • 79960162517 scopus 로고    scopus 로고
    • Epigenetics lights up the obesity field
    • Marti A, Ordovas J: Epigenetics lights up the obesity field. Obes Facts 2011; 4: 187-190.
    • (2011) Obes Facts , vol.4 , pp. 187-190
    • Marti, A.1    Ordovas, J.2
  • 15
  • 17
    • 0026735063 scopus 로고
    • Protein isoprenylation and methylation at carboxyl-terminal cysteine residues
    • Clarke S: Protein isoprenylation and methylation at carboxyl-terminal cysteine residues. Annu Rev Biochem 1992; 61: 355-386.
    • (1992) Annu Rev Biochem , vol.61 , pp. 355-386
    • Clarke, S.1
  • 18
    • 0026744521 scopus 로고
    • Isoprenylation and carboxylmethylation in small GTP-binding proteins of pheochromocytoma (PC-12) cells
    • Lerner S, Haklai R, Kloog Y: Isoprenylation and carboxylmethylation in small GTP-binding proteins of pheochromocytoma (PC-12) cells. Cell Mol Neurobiol 1992; 12: 333-351.
    • (1992) Cell Mol Neurobiol , vol.12 , pp. 333-351
    • Lerner, S.1    Haklai, R.2    Kloog, Y.3
  • 19
    • 0020658546 scopus 로고
    • Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy
    • Pettitt DJ, Baird HR, Aleck KA, Bennett PH, Knowler WC: Excessive obesity in offspring of Pima Indian women with diabetes during pregnancy. N Engl J Med 1983; 308: 242-245.
    • (1983) N Engl J Med , vol.308 , pp. 242-245
    • Pettitt, D.J.1    Baird, H.R.2    Aleck, K.A.3    Bennett, P.H.4    Knowler, W.C.5
  • 22
    • 78049318886 scopus 로고    scopus 로고
    • The Dutch Hunger Winter and the developmental origins of health and disease
    • Schulz LC: The Dutch Hunger Winter and the developmental origins of health and disease. Proc Natl Acad Sci USA 2010; 107: 16757-16758.
    • (2010) Proc Natl Acad Sci USA , vol.107 , pp. 16757-16758
    • Schulz, L.C.1
  • 24
    • 84859641098 scopus 로고    scopus 로고
    • DNA methylation differences at growth related genes correlate with birth weight: A molecular signature linked to developmental origins of adult disease?
    • Turan N, Ghalwash MF, Katari S, Coutifaris C, Obradovic Z, Sapienza C: DNA methylation differences at growth related genes correlate with birth weight: a molecular signature linked to developmental origins of adult disease? BMC Med Genomics 2012; 5: 10.
    • (2012) BMC Med Genomics , vol.5 , pp. 10
    • Turan, N.1    Ghalwash, M.F.2    Katari, S.3    Coutifaris, C.4    Obradovic, Z.5    Sapienza, C.6
  • 27
    • 0029840221 scopus 로고    scopus 로고
    • Rape-related pregnancy: Estimates and descriptive characteristics from a national sample of women
    • discussion 324-325
    • Holmes MM, Resnick HS, Kilpatrick DG, Best CL: Rape-related pregnancy: estimates and descriptive characteristics from a national sample of women. Am J Obstet Gynecol 1996; 175: 320-324; discussion 324-325.
    • (1996) Am J Obstet Gynecol , vol.175 , pp. 320-324
    • Holmes, M.M.1    Resnick, H.S.2    Kilpatrick, D.G.3    Best, C.L.4
  • 33
    • 33846011358 scopus 로고    scopus 로고
    • Long-term effects of nutritional programming of the embryo and fetus: Mechanisms and critical windows
    • Symonds ME, Stephenson T, Gardner DS, Budge H: Long-term effects of nutritional programming of the embryo and fetus: mechanisms and critical windows. Reprod Fertil Dev 2007; 19: 53-63.
    • (2007) Reprod Fertil Dev , vol.19 , pp. 53-63
    • Symonds, M.E.1    Stephenson, T.2    Gardner, D.S.3    Budge, H.4
  • 34
    • 84870419438 scopus 로고    scopus 로고
    • Glucose as a fetal nutrient: Dynamic regulation of several glucose transporter genes by DNA methylation in the human placenta across gestation
    • Novakovic B, Gordon L, Robinson WP, Desoye G, Saffery R: Glucose as a fetal nutrient: dynamic regulation of several glucose transporter genes by DNA methylation in the human placenta across gestation. J Nutr Biochem 2013; 24: 282-288.
    • (2013) J Nutr Biochem , vol.24 , pp. 282-288
    • Novakovic, B.1    Gordon, L.2    Robinson, W.P.3    Desoye, G.4    Saffery, R.5
  • 35
    • 63449117870 scopus 로고    scopus 로고
    • Placental-fetal glucose exchange and fetal glucose metabolism
    • discussion 339-340
    • Hay WW Jr: Placental-fetal glucose exchange and fetal glucose metabolism. Trans Am Clin Climatol Assoc 2006; 117: 321-339; discussion 339-340.
    • (2006) Trans Am Clin Climatol Assoc , vol.117 , pp. 321-339
    • Hay Jr., W.W.1
  • 40
    • 30544449722 scopus 로고    scopus 로고
    • Fetal, infant and childhood growth: Relationships with body composition in Brazilian boys aged 9 years
    • Wells JC, Hallal PC, Wright A, Singhal A, Victora CG: Fetal, infant and childhood growth: relationships with body composition in Brazilian boys aged 9 years. Int J Obes (Lond) 2005; 29: 1192-1198.
    • (2005) Int J Obes (Lond) , vol.29 , pp. 1192-1198
    • Wells, J.C.1    Hallal, P.C.2    Wright, A.3    Singhal, A.4    Victora, C.G.5
  • 45
    • 84872113159 scopus 로고    scopus 로고
    • Promoter methylation of serotonin transporter gene is associated with obesity measures: A monozygotic twin study
    • Zhao J, Goldberg J, Vaccarino V: Promoter methylation of serotonin transporter gene is associated with obesity measures: a monozygotic twin study. Int J Obes (Lond) 2013; 37: 140-145.
    • (2013) Int J Obes (Lond) , vol.37 , pp. 140-145
    • Zhao, J.1    Goldberg, J.2    Vaccarino, V.3
  • 48
    • 79959650031 scopus 로고    scopus 로고
    • DNA methylation variability at growth-related imprints does not contribute to overweight in monozygotic twins discordant for BMI
    • Souren NY, Tierling S, Fryns JP, Derom C, Walter J, Zeegers MP: DNA methylation variability at growth-related imprints does not contribute to overweight in monozygotic twins discordant for BMI. Obesity (Silver Spring) 2011; 19: 1519-1522.
    • (2011) Obesity (Silver Spring) , vol.19 , pp. 1519-1522
    • Souren, N.Y.1    Tierling, S.2    Fryns, J.P.3    Derom, C.4    Walter, J.5    Zeegers, M.P.6
  • 49
    • 84863053794 scopus 로고    scopus 로고
    • Global DNA methylation is associated with insulin resistance: A monozygotic twin study
    • Zhao J, Goldberg J, Bremner JD, Vaccarino V: Global DNA methylation is associated with insulin resistance: a monozygotic twin study. Diabetes 2012; 61: 542-546.
    • (2012) Diabetes , vol.61 , pp. 542-546
    • Zhao, J.1    Goldberg, J.2    Bremner, J.D.3    Vaccarino, V.4
  • 52
    • 34247473478 scopus 로고    scopus 로고
    • The epigenetic basis of twin discordance in agerelated diseases
    • Poulsen P, Esteller M, Vaag A, Fraga MF: The epigenetic basis of twin discordance in agerelated diseases. Pediatr Res 2007; 61: 38R- 42R.
    • (2007) Pediatr Res , vol.61
    • Poulsen, P.1    Esteller, M.2    Vaag, A.3    Fraga, M.F.4
  • 53
    • 34447498828 scopus 로고    scopus 로고
    • Integration of physiological and molecular mechanisms of the developmental origins of adult disease: New concepts and insights
    • Symonds ME: Integration of physiological and molecular mechanisms of the developmental origins of adult disease: new concepts and insights. Proc Nutr Soc 2007; 66: 442-450.
    • (2007) Proc Nutr Soc , vol.66 , pp. 442-450
    • Symonds, M.E.1
  • 54
    • 84863553003 scopus 로고    scopus 로고
    • The obesity epidemic: From the environment to epigenetics - Not simply a response to dietary manipulation in a thermoneutral environment
    • Symonds ME, Sebert S, Budge H: The obesity epidemic: from the environment to epigenetics - not simply a response to dietary manipulation in a thermoneutral environment. Front Genet 2011; 2: 24.
    • (2011) Front Genet , vol.2 , pp. 24
    • Symonds, M.E.1    Sebert, S.2    Budge, H.3
  • 59
    • 73449110929 scopus 로고    scopus 로고
    • Inter-individual variation of dietary fat-induced mesoderm specific transcript in adipose tissue within inbred mice is not caused by altered promoter methylation
    • Koza RA, Rogers P, Kozak LP: Inter-individual variation of dietary fat-induced mesoderm specific transcript in adipose tissue within inbred mice is not caused by altered promoter methylation. Epigenetics 2009; 4: 512-518.
    • (2009) Epigenetics , vol.4 , pp. 512-518
    • Koza, R.A.1    Rogers, P.2    Kozak, L.P.3
  • 60
    • 84865144872 scopus 로고    scopus 로고
    • Cell biology: Neither brown nor white
    • Cannon B, Nedergaard J: Cell biology: neither brown nor white. Nature 2012; 488: 286-287.
    • (2012) Nature , vol.488 , pp. 286-287
    • Cannon, B.1    Nedergaard, J.2
  • 62
    • 84873518501 scopus 로고    scopus 로고
    • Adaptive thermogenesis in adipocytes: Is beige the new brown?
    • Wu J, Cohen P, Spiegelman BM: Adaptive thermogenesis in adipocytes: is beige the new brown? Genes Dev 2013; 27: 234-250.
    • (2013) Genes Dev , vol.27 , pp. 234-250
    • Wu, J.1    Cohen, P.2    Spiegelman, B.M.3
  • 63
    • 64349121056 scopus 로고    scopus 로고
    • Transcriptional control of brown adipocyte development and physiological function - Of mice and men
    • Seale P, Kajimura S, Spiegelman BM: Transcriptional control of brown adipocyte development and physiological function - of mice and men. Genes Dev 2009; 23: 788-797.
    • (2009) Genes Dev , vol.23 , pp. 788-797
    • Seale, P.1    Kajimura, S.2    Spiegelman, B.M.3
  • 64
    • 77950264120 scopus 로고    scopus 로고
    • Brown fat and the myth of dietinduced thermogenesis
    • Kozak LP: Brown fat and the myth of dietinduced thermogenesis. Cell Metab 2010; 11: 263-267.
    • (2010) Cell Metab , vol.11 , pp. 263-267
    • Kozak, L.P.1
  • 66
    • 0030730891 scopus 로고    scopus 로고
    • Adipose tissue development during early postnatal life in ewe-reared lambs
    • Clarke L, Buss DS, Juniper DS, Lomax MA, Symonds ME: Adipose tissue development during early postnatal life in ewe-reared lambs. Exp Physiol 1997; 82: 1015-1027.
    • (1997) Exp Physiol , vol.82 , pp. 1015-1027
    • Clarke, L.1    Buss, D.S.2    Juniper, D.S.3    Lomax, M.A.4    Symonds, M.E.5
  • 67
    • 84885003077 scopus 로고    scopus 로고
    • The developmental transition of ovine adipose tissue through early life
    • E-pub ahead of print
    • Pope M, Budge H, Symonds ME: The developmental transition of ovine adipose tissue through early life. Acta Physiol (Oxf) 2013, E-pub ahead of print.
    • (2013) Acta Physiol (Oxf)
    • Pope, M.1    Budge, H.2    Symonds, M.E.3
  • 68
    • 67651149737 scopus 로고    scopus 로고
    • Adipose tissue inflammation: Developmental ontogeny and consequences of gestational nutrient restriction in offspring
    • Sharkey D, Symonds ME, Budge H: Adipose tissue inflammation: developmental ontogeny and consequences of gestational nutrient restriction in offspring. Endocrinology 2009; 150: 3913-3920.
    • (2009) Endocrinology , vol.150 , pp. 3913-3920
    • Sharkey, D.1    Symonds, M.E.2    Budge, H.3
  • 69
    • 0346656883 scopus 로고    scopus 로고
    • Endocrine and nutritional regulation of fetal adipose tissue development
    • Symonds ME, Mostyn A, Pearce S, Budge H, Stephenson T: Endocrine and nutritional regulation of fetal adipose tissue development. J Endocrinol 2003; 179: 293-299.
    • (2003) J Endocrinol , vol.179 , pp. 293-299
    • Symonds, M.E.1    Mostyn, A.2    Pearce, S.3    Budge, H.4    Stephenson, T.5
  • 71
    • 0033958449 scopus 로고    scopus 로고
    • Effect of delivery temperature on endocrine stimulation of thermoregulation in lambs born by cesarean section
    • Symonds ME, Bird JA, Sullivan C, Wilson V, Clarke L, Stephenson T: Effect of delivery temperature on endocrine stimulation of thermoregulation in lambs born by cesarean section. J Appl Physiol 2000; 88: 47-53.
    • (2000) J Appl Physiol , vol.88 , pp. 47-53
    • Symonds, M.E.1    Bird, J.A.2    Sullivan, C.3    Wilson, V.4    Clarke, L.5    Stephenson, T.6
  • 73
    • 84884992692 scopus 로고    scopus 로고
    • The impact of cesarean section on offspring overweight and obesity: A systematic review and meta-analysis
    • E-pub ahead of print
    • Li HT, Zhou YB, Liu JM: The impact of cesarean section on offspring overweight and obesity: a systematic review and meta-analysis. Int J Obes (Lond) 2012, E-pub ahead of print.
    • (2012) Int J Obes (Lond)
    • Li, H.T.1    Zhou, Y.B.2    Liu, J.M.3
  • 74
    • 77952060999 scopus 로고    scopus 로고
    • Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue
    • Shore A, Karamitri A, Kemp P, Speakman JR, Lomax MA: Role of Ucp1 enhancer methylation and chromatin remodelling in the control of Ucp1 expression in murine adipose tissue. Diabetologia 2010; 53: 1164-1173.
    • (2010) Diabetologia , vol.53 , pp. 1164-1173
    • Shore, A.1    Karamitri, A.2    Kemp, P.3    Speakman, J.R.4    Lomax, M.A.5
  • 75
    • 0043093697 scopus 로고    scopus 로고
    • Transposable elements: Targets for early nutritional effects on epigenetic gene regulation
    • Waterland RA, Jirtle RL: Transposable elements: targets for early nutritional effects on epigenetic gene regulation. Mol Cell Biol 2003; 23: 5293-5300.
    • (2003) Mol Cell Biol , vol.23 , pp. 5293-5300
    • Waterland, R.A.1    Jirtle, R.L.2
  • 76
    • 0031873353 scopus 로고    scopus 로고
    • Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice
    • Wolff GL, Kodell RL, Moore SR, Cooney CA: Maternal epigenetics and methyl supplements affect agouti gene expression in Avy/a mice. FASEB J 1998; 12: 949-957.
    • (1998) FASEB J , vol.12 , pp. 949-957
    • Wolff, G.L.1    Kodell, R.L.2    Moore, S.R.3    Cooney, C.A.4
  • 77
    • 0030912476 scopus 로고    scopus 로고
    • Components of the AIN-93 diets as improvements in the AIN-76A diet
    • Reeves PG: Components of the AIN-93 diets as improvements in the AIN-76A diet. J Nutr 1997; 127: 838S-841S.
    • (1997) J Nutr , vol.127
    • Reeves, P.G.1
  • 78
    • 65549166994 scopus 로고    scopus 로고
    • Nutrition and its contribution to obesity and diabetes: A life-course approach to disease prevention?
    • Symonds ME: Nutrition and its contribution to obesity and diabetes: a life-course approach to disease prevention? Proc Nutr Soc 2009; 68: 71-77.
    • (2009) Proc Nutr Soc , vol.68 , pp. 71-77
    • Symonds, M.E.1
  • 81
    • 45549097738 scopus 로고    scopus 로고
    • Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1
    • Park JH, Stoffers DA, Nicholls RD, Simmons RA: Development of type 2 diabetes following intrauterine growth retardation in rats is associated with progressive epigenetic silencing of Pdx1. J Clin Invest 2008; 118: 2316-2324.
    • (2008) J Clin Invest , vol.118 , pp. 2316-2324
    • Park, J.H.1    Stoffers, D.A.2    Nicholls, R.D.3    Simmons, R.A.4
  • 82
    • 40649092301 scopus 로고    scopus 로고
    • Intrauterine growth restriction in a rodent model and developmental programming of the metabolic syndrome: A critical appraisal of the experimental evidence
    • Neitzke U, Harder T, Schellong K, Melchior K, Ziska T, Rodekamp E, Dudenhausen JW, Plagemann A: Intrauterine growth restriction in a rodent model and developmental programming of the metabolic syndrome: a critical appraisal of the experimental evidence. Placenta 2008; 29: 246-254.
    • (2008) Placenta , vol.29 , pp. 246-254
    • Neitzke, U.1    Harder, T.2    Schellong, K.3    Melchior, K.4    Ziska, T.5    Rodekamp, E.6    Dudenhausen, J.W.7    Plagemann, A.8
  • 83
    • 77952061606 scopus 로고    scopus 로고
    • Experimental intrauterine growth restriction induces alterations in DNA methylation and gene expression in pancreatic islets of rats
    • Thompson RF, Fazzari MJ, Niu H, Barzilai N, Simmons RA, Greally JM: Experimental intrauterine growth restriction induces alterations in DNA methylation and gene expression in pancreatic islets of rats. J Biol Chem 2010; 285: 15111-15118.
    • (2010) J Biol Chem , vol.285 , pp. 15111-15118
    • Thompson, R.F.1    Fazzari, M.J.2    Niu, H.3    Barzilai, N.4    Simmons, R.A.5    Greally, J.M.6
  • 84
    • 82355190897 scopus 로고    scopus 로고
    • The early programming of metabolic health: Is epigenetic setting the missing link?
    • Sebert S, Sharkey D, Budge H, Symonds ME: The early programming of metabolic health: is epigenetic setting the missing link? Am J Clin Nutr 2011; 94: 1953S-1958S.
    • (2011) Am J Clin Nutr , vol.94
    • Sebert, S.1    Sharkey, D.2    Budge, H.3    Symonds, M.E.4
  • 86
    • 80053099289 scopus 로고    scopus 로고
    • Maternal diet, aging and diabetes meet at a chromatin loop
    • Ozanne SE, Sandovici I, Constancia M: Maternal diet, aging and diabetes meet at a chromatin loop. Aging 2011; 3: 548-554.
    • (2011) Aging , vol.3 , pp. 548-554
    • Ozanne, S.E.1    Sandovici, I.2    Constancia, M.3
  • 88
    • 84878239490 scopus 로고    scopus 로고
    • Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes
    • Sacks H, Symonds ME: Anatomical locations of human brown adipose tissue: Functional relevance and implications in obesity and type 2 diabetes. Diabetes 2013; 62: 1783-1790.
    • (2013) Diabetes , vol.62 , pp. 1783-1790
    • Sacks, H.1    Symonds, M.E.2
  • 89
    • 84867877438 scopus 로고    scopus 로고
    • Thermal imaging to assess age-related changes of skin temperature within the supraclavicular region co-locating with brown adipose tissue in healthy children
    • Symonds ME, Henderson K, Elvidge L, Bosman C, Sharkey D, Perkins AC, Budge H: Thermal imaging to assess age-related changes of skin temperature within the supraclavicular region co-locating with brown adipose tissue in healthy children. J Pediatr 2012; 161: 892-898.
    • (2012) J Pediatr , vol.161 , pp. 892-898
    • Symonds, M.E.1    Henderson, K.2    Elvidge, L.3    Bosman, C.4    Sharkey, D.5    Perkins, A.C.6    Budge, H.7
  • 90
    • 84871199035 scopus 로고    scopus 로고
    • How promising is thermal imaging in the quest to combat obesity?
    • Symonds ME, Budge H: How promising is thermal imaging in the quest to combat obesity? Imaging Med 2012; 4: 589-591.
    • (2012) Imaging Med , vol.4 , pp. 589-591
    • Symonds, M.E.1    Budge, H.2
  • 91
    • 84882687180 scopus 로고    scopus 로고
    • Effects of overfeeding naturally-mated adolescent ewes on maternal, fetal, and postnatal lamb growth
    • Peel RK, Eckerle GJ, Anthony RV: Effects of overfeeding naturally-mated adolescent ewes on maternal, fetal, and postnatal lamb growth. J Anim Sci 2012; 90: 3698-3708.
    • (2012) J Anim Sci , vol.90 , pp. 3698-3708
    • Peel, R.K.1    Eckerle, G.J.2    Anthony, R.V.3
  • 92
    • 0029744945 scopus 로고    scopus 로고
    • Nutrient partitioning and fetal growth in rapidly growing adolescent ewes
    • Wallace JM, Aitken RP, Cheyne MA: Nutrient partitioning and fetal growth in rapidly growing adolescent ewes. J Reprod Fertil 1996; 107: 183-190.
    • (1996) J Reprod Fertil , vol.107 , pp. 183-190
    • Wallace, J.M.1    Aitken, R.P.2    Cheyne, M.A.3


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.