The genetic and genomic era provides a promising opportunity of dissecting genetic etiology of complex diseases or traits through investigating gene-environment interactions, predicting disease risk, improving prevention and intervention to promote precision medicine. In the past decades, more than 1,000 common genetic variants have been identified for many complex diseases and traits through a large number of genome-wide association studies. The genetic and genomic data provide many exciting opportunities as well as challenges in data analysis. We have been developing and applying statistical/analytical approaches for common and rare variant analysis of whole-genome sequencing association studies, analysis of polygenic traits, and integrative analysis of different types of environmental, genetic and genomic data as well as conducting genetic epidemiological studies mainly for lung cancer and hypertension/insulin resistance.

Lung cancer

• Chen KY, Hsiao CF, Chang GC, Tsai YH, Su WC, Chen YM, Huang MS, Tsai FY, Jiang SS, Chang IS, Chen CY, Hsiung CA⁺, Chen CJ, Yang PC,⁺. EGFR polymorphisms, hormone replacement therapy and lung adenocarcinoma risk: analysis from a genome-wide association study in never-smoking women. Carcinogenesis 2013; 34(3): 612-9. (⁺ These authors contributed equally to this work)
• Machiela MJ ^†, Hsiung CA ^†, Shu XO ^†, Seow WJ ^†, Wang Z ^†, Matsuo K ^†, Hong YC ^†, Seow A ^†, Wu C ^†, Hosgood HD 3rd ^†,Chen K ^†, Wang JC ^†, …., ., Fraumeni Jr JF, Zheng W, Lin D, Chanock SJ, Rothman N, Lan Q. Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: a report from the female lung cancer consortium in Asia. International Journal of Cancer 2015; 137(2): 311-9 († These authors contributed equally to this work)
• Wu X, Wang L, Ye Y, Aakre JA, Pu X, Chang GC, Yang PC, …, Minna JD, Hong WK, Hildebrandt MA^#, Hsiung CA^#, Yang P.^# Genome-wide association study of genetic predictors of overall survival for non-small cell lung cancer in never smokers. Cancer Research 2013; 73(13): 4028-38. (# = these authors contributed equally to this work)
• Chang CH, Hsiao CF, Yeh YM, Chang GC, Tsai YH, Chen YM, Huang MS, Chen HL, Li YJ, Yang PC, Chen CJ, Hsiung CA⁺, Su WC⁺. Circulating interleukin-6 level is a prognostic marker for survival in advanced nonsmall cell lung cancer patients treated with chemotherapy. International Journal of Cancer 2013; 132(9): 1977-85.
• Chen KY^#, Hsiao CF^#, Chang GC, Tsai YH, Su WC, Chen YM, Huang MS, Hsiung CA⁺, Chen CJ, Yang PC⁺. EGFR polymorphisms, hormone replacement therapy and lung adenocarcinoma risk: analysis from a genome-wide association study in never-smoking women. Carcinogenesis 2013; 34(3): 612-9. (+: contributed equally, #: joint first authors)
• Lan Q⁺, Hsiung CA⁺, Matsuo K, Hong YC, Seow A, Wang Z, …, Yang PC, Zhou B, Shin MH, Fraumeni JF Jr, Lin D, Chanock SJ, Rothman N. Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia. Nature Genetics 2012; 44(12): 1330-5 (contributed equally with the first author)

Hypertension and insulin resistance

• Wu Y, Waite LL, Jackson AU, Sheu WH, Buyske S, Absher D, …, Kooperberg C, Assimes TL, Crawford DC, Hsiung CA⁺, North KE⁺, Mohlke KL⁺. Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained. PloS Genetics 2013; 9(3): e1003379. (+: joint senior authors)
• Assimes TL, Lee IT, Juang JM, Guo X, Wang TD, Kim ET, Lee WJ, Absher D, Chiu YF, Hsu CC, Chuang LM, Quertermous T, Hsiung CA, Rotter JI, Sheu WH, Chen YD, Taylor KD. Genetics of Coronary Artery Disease in Taiwan: A Cardiometabochip Study by the Taichi Consortium. PloS one 2016; 11(3): e0138014.
• Wen W, Zheng W, Okada Y, Takeuchi F, Tabara Y, Hwang JY, Dorajoo R, Li H, Tsai FJ, Yang X, He J, Wu Y, He M, …., Hsiung CA, ….., Wu T, Mohlke KL, Gu D, Mo Z, Wu JY, Lin X, Miki T, Tai ES, Lee JY, Kato N, Shu XO, Tanaka T. Meta-analysis of genome-wide association studies in East Asian-ancestry populations identifies four new loci for body mass index. Human Molecular genetics 2014; 23(20): 5492-504.
• Wu Y, Gao H, Li H, Tabara Y, Nakatochi M, Chiu YF, ….., Hsiung CA, …., Jee SH, Chuang LM, Miki T, Yokota M, Lin X, Mohlke KL, Tai ES. A meta-analysis of genome-wide association studies for adiponectin levels in East Asians identifies a novel locus near WDR11-FGFR2. Human Molecular Genetics 2014; 23(4): 1108-19.
• Kuo JZ, Sheu WH, Assimes TL, Hung YJ, Absher D, Chiu YF, Mak J, …, Chuang LM, Hsiung CA, Quertermous T, Rotter JI, Chen YD. Trans-ethnic fine mapping identifies a novel independent locus at the 3′ end of CDKAL1 and novel variants of several susceptibility loci for type 2 diabetes in a Han Chinese population. Diabetologia 2013; 56(12): 2619-28.

We have developed statistical methods for identifying common/rare variants associated with complex diseases.

• Chien LC, Hsu FC, Bowden DW, Chiu YF. Generalization of Rare Variant Association Tests for Longitudinal Family Studies. Genetic Epidemiology 2016; 40(2): 101-12..
• Chien LC, Chiu YF, Liang KY, Chuang LM. Simultaneous estimation of the locations and effects of multiple disease loci in case-control studies. Biostatistics (Oxford, England) 2015; 16(2): 222-39.
• Chung RH, Tsai WY, Martin ER. Family-based association test using both common and rare variants and accounting for directions of effects for sequencing data. PloS One 2014; 9(9): e107800.
• Fang YH, Chiu YF. A novel support vector machine-based approach for rare variant detection. PloS One 2013; 8(8): e71114.

We have developed efficient gene-based tests and gene-gene interaction tests and algorithms.

• Sung PY, Wang YT, Yu YW, Chung RH. An efficient gene-gene interaction test for genome-wide association studies in trio families. Bioinformatics (Oxford, England) 2016
• Wang YT, Sung PY, Lin PL, Yu YW, Chung RH. A multi-SNP association test for complex diseases incorporating an optimal P-value threshold algorithm in nuclear families. BMC Genomics 2015; 16: 381.
• Fang YH, Chiu Y SVM-based generalized multifactor dimensionality reduction approaches for detecting gene-gene interactions in family studies. Genetic Epidemiology 2012; 36(2): 88-98.

We have identified genetic variants associated with complex traits.

• Hsieh CH, Chung RH, Lee WJ, et al. Effect of Common Genetic Variants of Growth Arrest-Specific 6 Gene on Insulin Resistance, Obesity and Type 2 Diabetes in an Asian Population. PloS One 2015; 10(8): e0135681..
• Chang TJ, Chiu YF, Sheu WH, et al. Genetic polymorphisms of PCSK2 are associated with glucose homeostasis and progression to type 2 diabetes in a Chinese population. Scientific Reports 2015; 5: 14380.

We have discovered genetic susceptibility and/or gene-environment interactions on preterm birth.

• Liu X, Wang G, Hong X, Tsai HJ, et al. Associations between gene polymorphisms in fatty acid metabolism pathway and preterm delivery in a US urban black population. Human Genetics 2012; 131(3): 341-51.
• Tsai HJ*, Hong X, Chen J, et al. Role of African ancestry and gene-environment interactions in predicting preterm birth. Obstetrics and Gynecology 2011; 118(5): 1081-9.
• Tsai HJ*, Yu Y, Zhang S, et al. Association of genetic ancestry with preterm delivery and related traits among African American mothers. American Journal of Obstetrics and Gynecology 2009; 201(1): 94.e1-10.

We have identified candidate genes associated with substance use in an Asian population.

• Liao DL, Cheng MC, Lai CH, Tsai HJ, Chen CH. Comparative gene expression profiling analysis of lymphoblastoid cells reveals neuron-specific enolase gene (ENO2) as a susceptibility gene of heroin dependence. Addiction Biology 2014; 19(1): 102-10.
• Tsai HJ, Wang SC, Liu SW, et al. Assessment of CYP450 genetic variability effect on methadone dose and tolerance. Pharmacogenomics 2014; 15(7): 977-86.
• Tsai HJ, Wang SC, Tian JN, et al. PXR polymorphisms interacted with CYP2B6 polymorphisms on methadone metabolites. Journal of Clinical Psychopharmacology 2013; 33(1): 137-40.