Hank Juo, M.D., Ph.D.
A major goal of functional genomics is the mapping and identifcation of genes conferring susceptibility to common diseases. Statistical genetics and genetic epidemiology are essential components of disease gene mapping. New statistical methods and approaches are being developed continuously to incorporate new genetic technologies. The specific statistical approaches and study design needed to map disease genes varies with the particular research question, the population, and the disease under analysis. Our laboratory currently uses family linkage, population association, and linkage disequilibrium methods to map and identify disease genes contributing to stroke/cardiovascular disease, breast cancer, melanoma, bipolar disorder, and celiac disease.
Stroke/cardiovascular disease. Our laboratory has been involved in two major stroke/cardiovascular disease research projects: the NOMASS and CARDIA studies. We are interested in looking for genes regulating intermediate phenotypes such as serum lipid levels and carotid artery intima-media thickness. This approach dissects the complexity of clinical events into less complex traits, and will facilitate gene discovery. A recent finding from our group shows a promoter polymorphism of the MTP gene influences the LDL and apoB levels in young African American men enrolled in the CARDIA study. We plan to test for the genetic effect in African American women and in whites. Since the subjects in CARDIA still are being followed up, we will be able to examine these effects as the population ages.
Breast cancer/melanoma. The life-time risk of breast cancer is 12% in Caucasians. Although two breast cancer genes, BRCA1 and BRCA2, have been cloned, they only account for approximately 20 to 30 % of familial breast cancer. We are interested in discovering novel breast cancer genes for the non-BRCA1/2 families. Our laboratory has been involved in the Nordic/NIH Breast Cancer Consortium, and this collaboration recently mapped a novel breast cancer gene to chromosome 13q21-22. We also collaborate with another breast cancer research team led by Dr. Ruby Senie of the Department of Epidemiology in investigating novel breast cancer genes in Chinese/Koreans and Ashkenazi Jews.
The life-time risk of melanoma in Australia is 4-5% and one tenth of the cases are considered familial. The risk in Australians is much higher than in the North European population. Approximately 20-40% of families segregate the known melanoma gene, CDKN2A (p16). We have been working with an international research team, including scientists from Australia, USA, French, Sweden, UK and Netherlands., which is responsible for all of the genetic analyses of melanoma families. The primary goal of this international collaboration is to disclose other melanoma genes.
Bipolar disorder. Bipolar disorder is a major public health concern owing to a lifetime prevalence of 0.5% to 1.5% and substantial morbidity and mortality. We are engaged in an ongoing bipolar genetic study in collaboration with the Departments of Psychiatry at Columbia University and Hadassah-Hebrew University in Israel. We have identified the largest number of multigenerational bipolar pedigrees of any reported study. A series of papers have been published based on this dataset. We recently finished a genome wide linkage analysis and a fine mapping project on chromosome 21. Several projects are underway to follow up on these results.
Celiac disease. Celiac disease (CD) is a multifactorial disorder of the small intestine resulting from intolerance to prolamins in wheat, barley, and rye. The prevalence of CD was once thought to be below 1 in 1000. However, recent data suggest a much higher prevalence of 0.4 to 1%. It has long been known that HLA class II loci are involved in susceptibility to CD. Evidence suggests that a non-HLA locus is also likely to be involved in disease pathogenesis. We are engaged in a collaboration with investigators in the Department of Gastroenterology and in Finland to study the non-HLA locus involved in CD.
Dr. Juo received his MD degree from Kaohsiung Medical University in Taiwan in 1989. He completed a residency training in neurology in Taiwan in 1992. He earned the MS degree in Epidemiology from Harvard University in 1994, and Ph.D. in Human Genetics/Genetic Epidemiology from Johns Hopkins University in 1997. Dr. Juo completed post-doctoral training in statistical genetics with Drs. Joan Bailey-Wilson at the NIH/National Genome Research Institute (NHGRI) and Jurg Ott at Rockefeller University. In 1999, Dr. Juo took his current position in the Columbia Genome Center, and in 2001 was also appointed in the Department of Epidemiology in Genomics.
Doehring CB, Sanda MG, Partin AW, Sauvageot J, Juo SH, Beaty TH, Epstein JI, Hill G, Walsh PC. Histopathologic Characterization of Hereditary Benign Prostatic Hyperplasia. Urology. 48(4):650-3, 1996
Juo SH, Beaty TH, Kwiterovich PO Jr. Etiologic Heterogeneity of Hyperapobetalipoproteinemia (HyperapoB): The Results From Segregation Analysis in Families Enriched for Coronary Artery Disease. Arterioscler Thromb Vasc Biol. 17: 2729-2736, 1997.
Juo SH, Beaty TH, Duffy LD, Maestri NE, Prenger VL , Zeiger J, Lei HH, Coresh J. A Comprehensive Analysis of a Common Disease and Its Underlying Traits. Genet Epidemiol. 14:815-820, 1997
Juo SH, Beaty TH, Xu J, Prenger VL, Coresh J, Kwiterovich PO Jr. Segregation Analysis of Two-Locus Models Regulating Apolipoprotein-AI Levels. Genet Epidemiol. 15:73-86, 1998
Juo SH, Bredie SJH, Kiemeney LA, Demacker PNM, Stalenhoef AFH. A Common Genetic Mechanism Determine Plasma Apolipoprotein B Levels and Dense LDL Subfraction Distribution in Familial Combined Hyperlipidemia. Am J Hum Genet. 63:586-594, 1998
Juo SH, Beaty TH, Duffy D, Coresh J, Kwiterovich PO Jr. No Common Major Gene for Apolipoprotein A-I and HDL3-C Levels: Results From Bivariate Segregation Analysis. Genet Epidemiol. 16:54-68, 1999
Juo SH, Wyszynski DF, Beaty TH, Huang HY, Bailey-Wilson JE. Mild Association Between the A/G Polymorphism in the Promoter of the Apolipoprotein A-I Gene and Apolipoprotein A-I levels: A Meta-analysis. Am J Med Genet. 82:235-241, 1999
Stephan DA, Gillanders E, Vanderveen D, Fraes-Lutz D, Wistow G, Van Auken A, Quesenberry MI, Robbins CM, Bailey-Wilson J, Juo SH, Trent JM, Smith L, Brownstein MJ. Mutation in gD-crystallin in a Kindred With Progressive Juvenile-onset Punctate Cataracts. Proc Natl. Acad. Sci. USA 96:1008-12, 1999.
De Oliveira e Silva ER, Kong M, Han Z, Starr C, Kass EM, Juo SH, Foster D, Dansky HM, Merkel M, Cundey K, Brinton EA, Breslow JL, Smith JD. Metabolic and Genetic Determinants of HDL Metabolism and Hepatic Lipase Activity in Normolipidemic Females. J Lipid Res. 40:1211-1221, 1999.
Juo SH, Pugh EW, Baffoe-Bonnie A, Kingman A, Sorant AJM, Klein A, O’Neill J, Mathias R, Wilson AF, Bailey-Wilson JE. Possible Linkage of Alcoholism, Monoamine Oxidase (MAO) Activity and P300 Amplitude to Chromosome 12q24. Genet Epidemiol. 17 Suppl 1:S193-8, 1999
Barnes KC, Freidhoff LR, Nickel R, Chiu YF, Juo SH, Hizawa N, Naidu RP, Ehrlich E, Duffy DL, Schou C, Levett PN, Marsh DG, Beaty TH. Dense Mapping of Chromosome 12q13.2-q23.3 and Linkage to Asthma and Atopy. J Allergy Clin Immunol 104(2 Pt 1):485-491, 1999
Appukuttan B, Gillanders E, Juo SH, Freas-Lutz D, Ott S, Sood R, Van Auken A, Bailey-Wilson J, Wang X, Patel R, Robbins CM, Chung M, Annett G, Weinberg K, Borchert M, Trent JM, Brownstein MJ, Stout JT. Localization of a Gene for Duane’s Retraction Syndrome to Chromosome 2q31. Am J Hum Genet 65(6):1639-1646 1999
Juo SH, Han Z, Smith JD, Colangelo L, Liu K. A Common Polymorphism in the Promoter Region of the Microsomal Triglyceride Transfer Protein Gene Influences Cholesterol, Triglyceride and ApolipoproteinB Levels in Young African American Men: Results From the CARDIA Study Arterioscler Thromb Vasc Biol. 20(5):1316-22, 2000
Kainu T, Juo SH, Desper R., Schäffer AA, Bailey-Wilson JE, Kallioniemi OP, et al. Somatic deletions in hereditary breast cancers implicate 13q21 as a putative novel breast cancer susceptibility locus. Proc Natl. Acad. Sci. USA 97:9603-9608, 2000
Juo SH, Han Z, Smith JD, Colangelo L, Liu K. A Promoter Polymorphism of the Hepatic Lipase Gene Exclusively Influences HDL2 But Not HDL3 Cholesterol in Young African American Men: The CARDIA Study J Lipid Res. 42: 258-264, 2001
Liu JJ, Juo SH, Terwilliger JD, Grunn A, Tong XM, Brito M, Loth JE, Kanyas K, Lerer B, Endicott J, Penchaszadeh G, Gilliam TC, Baron M. A Follow-Up Linkage Study Supports Evidence for a Bipolar Affective Disorder Locus on Chromosome 21q22. Am J Med Genet. 2001;105(2):189-94, 2001
Slager SL, Juo SH, Durner M, Hodge SE. Markov Chain Monte Carlo Linkage Analysis: Effect of Bin Width on the Probability of Linkage. (in press) Genet