實驗室簡介

臺大基因體醫學研究中心 遺傳流行病學核心實驗室

實驗室簡介

基於本核心實驗室過去幾年來所成功建置的研究樣本及其生物檢體貯存設備、基因定型設備、以及遺傳流行病學分析軟體等基礎設施,本核心實驗室未來三年的具體目標為:

  1. 提供可做為大型關聯分析所需要的病例對照研究樣本或家族關聯研究樣本,以尋找複雜疾病的易感性基因;
  2. 促進以病例對照研究樣本或家族關聯研究樣本所進行的全基因關聯分析;
  3. 提供單一核苷酸多型性基因標誌的基因定型服務;
  4. 對於處理遺傳資料有困難的研究人員,提供最新的遺傳流行病學統計分析;
  5. 發展新型遺傳變異,如烤貝數變異多型性,之有效率辨識與定型方法。

本計畫之預期結果為:

  1. 藉由主動推廣、工作坊、研討會等方式促進遺傳流行病學研究;
  2. 對於社區樣本中常見之代謝症候群,可協助找出相關的基因變異以及脈絡因素;
  3. 藉由家族關聯研究可協助對於精神分裂症基因定位分析,並探討其內表型 (endophenotype) 在非臨床樣本中的特性;
  4. 協助學生、助理親手處理遺傳流行學學分析的訓練;
  5. 協助研究人員完成他們對於感興趣疾病的遺傳流行病學研究。

Introduction

On the basis of the study samples, genotyping equipment, and software for genetic epidemiological analysis that have been successfully installed in this core laboratory, the specific aims of this Core Laboratory can be summarized as follows:

  1. To provide large samples for association studies for the search for the susceptibility genes for complex diseases, including both population case-controls and family-based association study;
  2. To facilitate whole genome association studies based on either population case-control design or family-based association design;
  3. To provide service for the genotyping of SNP markers;
  4. To provide updated genetic epidemiological analyses for researchers who have the data but encounter difficult in making full utilization of the data;
  5. To develop efficient way for identifying new forms of genetic variations such as copy number polymorphisms (CNPs).

Ancipated results of this core laboratory are to:

  1. facilitae genetic epidemiological studies within the campus by means of active advocation, workshop, and collaboration;
  2. help identify important genetic variants as well as contextual variables that influence the risk of metabolic syndrome in a community sample of large sample size;
  3. help the gene mapping for schizophrenia by means of family-based association as well as schizophrenia-related endophenotype in non-clinical samples;
  4. help train more students and research assistants who can deal with genetic epidemiology via hands-on experience; and
  5. help researchers accomplish their genetic epidemiological investigation of the diseases they are interested in.

Reference

  1. RAbbott A (2000) Manhattan versus Reykjavik. Nature 406:340-342
  2. Arking DE, Pfeufer A, Post W, Kao WHL, Newton-Cheh C, Ikeda M, West K, Kashuk C, Akyol M, Perz S, Jalilzadeh S, Illig T, Gieger C, Guo C-Y, Larson MG, Wichmann HE, Marban E, O'Donnell CJ, Hirschhorn JN, Kaab S, Spooner PM, Meitinger T, Chakravarti A (2006) A common genetic variant in the NOS1 regulator NOS1AP modulates cardiac repolarization. Nature Genetics 38:644-651
  3. Badner JA, Gershon ES (2002) Meta-analysis of whole-genome linkage scans of bipolar disorder and schizophrenia. Molecular Psychiatry 7:405-411
  4. Botstein D, Risch N (2003) Discovering genotypes underlying human phenotypes: past successes for mednelian disease, future approaches for complex disease. Nature Genetics 33 (suppl):228-237
  5. Carlson CS, Eberle MA, Kruglyak L, Nickerson DA (2004) Mapping complex disease loci in whole-genome association studies. Nature 429:446-452
  6. Cervino AC, Hill AV (2000) Comparison of tests for association and linkage in incomplete families. American Journal of Human Genetics 67:120-132
  7. Chen CJ, Yu MW, Liaw YF, Wang LW, Chiamprasert S, Matin F, Hirvonen A, Bell DA, Santella RM (1996a) Chronic hepatitis B carriers with null genotypes of glutathione s-transferase M1 and T1 polymorphisms who are exposed to aflatoxin are at increased risk of hepatocellular carainoma. American Journal of Human Genetics 59:128-134
  8. Chen WJ, Loh EW, Hsu YP, Chen CC, Yu JM, Cheng AT (1996b) Alcohol-metabolising genes and alcoholism among Taiwanese Han men: independent effect of ADH2, ADH3 and ALDH2. British Journal of Psychiatry 168:762-767
  9. Crow TJ (2007) How and why genetic linkage has not solved the problem of psychosis: review and hypothesis. American Journal of Psychiatry 164:13-21
  10. Dewan A, Liu M, Hartman S, Zhang SS-M, Liu DTL, Zhao C, Tam POS, Chan WM, Lam DSC, Snyder M, Barnstable C, Pang CP, Hoh J (2006) HTRA1 promoter polymorphism in wet age-related macular degeneration. Science 314:989-992
  11. Faraone SV, Hwu H-G, Liu C-M, Chen WJ, Tsuang M-M, Liu S-K, Shieh M-H, Hwang T-J, Ou-Yang W-C, Chen C-Y, Chen C-C, Lin J-J, Chou FH-C, Chueh C-M, Liu W-M, Hall M-H, Su J, Van Eerdewegh P, Tsuang MT (2006) Genome scan of Han Chinese schizophrenia families from Taiwan: confirmation of linkage to 10q22.3. American Journal of Psychiatry 163:1760-1766
  12. Frayling TM (2007) Genome-wide association studies provide new insights into type 2 diabetes aetiology. Nat Rev Genet 8:657-662
  13. Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296:2225-2229
  14. Herbert A, Gerry NP, McQueen MB, Heid IM, Pfeufer A, Illig T, Wichmann HE, Meitinger T, Hunter D, Hu FB, Colditz G, Hinney A, Hebebrand J, Koberwitz K, Zhu X, Cooper R, Ardlie K, Lyon H, Hirschhorn JN, Laird NM, Lenburg ME, Lange C, Christman MF (2006) A common genetic variant is associated with adult and childhood obesity. Science 312:279-283
  15. Hwu H-G, Faraone SV, Liu C-M, Chen WJ, Liu S-K, Shieh M-H, Hwang T-J, Tsuang M-M, OuYang W-C, Chen C-Y, Chen C-C, Lin J-J, Chou FH-C, Chueh C-M, Liu W-M, Hall M-H, Tsuang MT (2005) Taiwan Schizophrenia Linkage Study: The field study. American Journal of Medical Genetics (Neuropsychiatric Genetics) 134B:30-36
  16. Ioannidis JPA, Trikalinos TA, Khoury MJ (2006) Implications of small effect sizes of individual genetic variants on the design and interpretation of genetic association studies of complex diseases. American Journal of Epidemiology 164:609-614
  17. Klein RJ, Zeiss C, Chew EY, Tsai J-Y, Sackler RS, Haynes C, Henning AK, SanGiovanni JP, Mane SM, Mayne ST, Bracken MB, Ferris FL, Ott J, Barnstable C, Hoh J (2005) Complement factor H polymorphism in age-related macular degeneration.[see comment]. Science 308:385-389
  18. Kruglyak L (1999) Prospects for whole-genome linkage disequilibrium mapping of common disease genes. Nature Genetics 22:139-144
  19. Kuschel B, Auranen A, McBride S, Novik KL, Antoniou A, Lipscombe JM, Day NE, Easton DF, Ponder BAJ, Pharoah PDP, Dunning A (2002) Variants in DNA double-strand break repair genes and breast cancer susceptibility. Human Molecular Genetics 11:1399-1407
  20. Laird NM, Lange C (2006) Family-based designs in the age of large-scale gene-association studies. Nature Reviews Genetics 7:385-394
  21. Lewis CM, Levinson DF, Wise LH, DeLisi LE, Straub RE, Hovatta I, Williams NM, et al. (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part II: Schizophrenia. American Journal of Human Genetics 73:34-48
  22. Liu C-M, Liu Y-L, Fann CS-J, Yang W-C, Wu J-Y, Hung S-I, Chen WJ, Chueh C-M, Liu W-M, Liu C-C, Hsieh M-H, Hwang T-J, Faraone SV, Tsuang MT, Hwu H-G (2007) No association evidence between schizophrenia and dystrobrevin-binding protein 1 (DTNBP1) in Taiwanese families. Schizophrenia Research 93:391-398
  23. McCarroll SA, Altshuler DM (2007) Copy-number variation and association studies of human disease. Nature Genetics 39:S37-S42
  24. Ostrander EA, Stanford JL (2000) Genetics of prostate cancer: too many loci, too few genes. American Journal of Human Genetics 67:1367-1375
  25. Pharoah PDP, Antoniou A, Bobrow M, Zimmern RL, Easton DF, Ponder BAJ (2002) Polygenic susceptibility to breast cancer and implications for prevention. Nature Genetics 31:33-36
  26. Plenge RM, Seielstad M, Padyukov L, Lee AT, Remmers EF, Ding B, Liew A, et al. (2007) TRAF1-C5 as a risk locus for rheumatoid arthritis: A genomewide study. N Engl J Med:NEJMoa073491
  27. Rebbeck TR (1997) Molecular epidemiology of the human glutathione S-transferase genotypes GSTM1 and GSTT1 in cancer susceptibility. Cancer Epidemiology, Biomarkers & Prevention 6:733-743
  28. Remmers EF, Plenge RM, Lee AT, Graham RR, Hom G, Behrens TW, de Bakker PIW, Le JM, Lee H-S, Batliwalla F, Li W, Masters SL, Booty MG, Carulli JP, Padyukov L, Alfredsson L, Klareskog L, Chen WV, Amos CI, Criswell LA, Seldin MF, Kastner DL, Gregersen PK (2007) STAT4 and the risk of rheumatoid arthritis and systemic lupus erythematosus. N Engl J Med 357:977-986
  29. Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273:1516-1517
  30. Ross RK, Pike MC, Coetzee GA, Reichardt JK, Yu MC, Feigelson H, Stanczyk FZ, Kolonel LN, Henderson BE (1998) Androgen metabolism and prostate cancer: establishing a model of genetic susceptibility. Cancer Research 58:4497-4504
  31. Segurado R, Detera-Wadleigh SD, Levinson DF, Lewis CM, Gill M, Nurnberger JI, Jr., Craddock N, et al. (2003) Genome scan meta-analysis of schizophrenia and bipolar disorder, part III: Bipolar disorder. American Journal of Human Genetics 73:49-62
  32. Sham PC, Cherny SS, Purcell S, Hewitt JK (2000) Power of linkage versus association analysis of quantitative traits, by use of variance-components models, for sibship data. American Journal of Human Genetics 66:1616-1630
  33. Skol AD, Scott LJ, Abecasis GR, Boehnke M (2006) Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 38:209-213
  34. Taylor JG, Choi EH, Foster CB, Chanock SJ (2001) Using genetic variation to study human disease. Trends in Molecular Medicine 7:507-512
  35. The Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447:661-678
  36. Tsuang H-C, Lin S-H, Liu SK, Hsieh M-H, Hwang TJ, Liu C-M, Hwu H-G, Chen WJ (2006) More severe sustained attention deficits in nonpsychotic siblings of multiplex schizophrenia families than in those of simplex ones. Schizophrenia Research 87:172-180
  37. Uhl GR, Liu Q-R, Walther D, Hess J, Naiman D (2001) Polysubstance abusevulnerability genes: Genome scans for association, using 1,004 subjects and 1,494 single-nucleotide polymorphisms. American Journal of Human Genetics 69:1290-1300
  38. Wacholder S, Rothman N, Caporaso N (2000) Population stratification in epidemiologic studies of common genetic variants and cancer: quantification of bias. JNCI Cancer Spectrum 92:1151-1158
  39. Wagenstaller J, Spranger S, Lorenz-Depiereux B, Kazmierczak B, Nathrath M, Wahl D, Heye B, Glaser D, Liebscher V, Meitinger T, Strom TM (2007) Copy-n umber variations measured by single-nucleotide-polymorphism oligonucleotide arrays in patients with mental retardation. American Journal of Human Genetics 81:768-779
  40. Wong KK, deLeeuw RJ, Dosanjh NS, Kimm LR, Cheng Z, Horsman DE, MacAulay C, Ng RT, Brown CJ, Eichler EE, Lam WL (2007) A comprehensive analysis of common copy-number variations in the human genome. American Journal of Human Genetics 80:91-104
  41. Yu MW, Chiu YH, Chiang YC, Chen CH, Lee TH, Santella RM, Chern HD, Liaw YF, Chen CJ (1999a) Plasma carotenoids, glutathione S-transferase M1 and T1 genetic polymorphisms, and risk of hepatocellular carcinoma: independent and interactive effects. American Journal of Epidemiology 149:621-629
  42. Yu MW, Yang SY, Chiu YH, Chiang YC, Liaw YF, Chen CJ (1999b) A p53 genetic polymorphism as a modulator of hepatocellular carcinoma risk in relation to chronic liver disease, familial tendency, and cigarette smoking in hepatitis B carriers. Hepatology 29:697-702
Genetic Epidemiology Core Laboratory, NTU Center for Genomic Medicine