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  5. Xiaofeng Zhu

Xiaofeng Zhu, PhD

Professor
Department of Population and Quantitative Health Sciences
School of Medicine
Faculty
Cleveland Institute for Computational Biology

Dr. Xiaofeng Zhu has developed many statistical methods in the areas of association analysis, population stratification and admixture mapping, and has had extensive experience in the design and analysis of genetic studies over the past 20 years. He and his colleagues suggested using principal components to summarize the genetic background information provided by a set of independent markers, this information to be used in association mapping for both quantitative and qualitative traits. Together with his colleagues, he performed the first admixture mapping study using microsatellite markers. His group has developed several novel statistical methods to identify rare variants contributing to the understanding of phenotypic variations. His group also developed cross-phenotype association (CPASSOC) that can integrate association evidence from summary statistics of multiple traits, either correlated or independent, continuous or binary, coming from the same or different studies. He leads the Continental Origins and Genetic Epidemiology Network (COGENT) consortium and has identified multiple loci associated with blood pressure traits in African-Ancestry population. He and his colleagues have also identified many genetic loci associated with sleep disorders. 

Teaching Information

Courses Taught

Population Genetics for Genetic Epidemiology
PQHS 480: Introduction to Mathematical Statistics

Research Information

Research Interests

Contributions to science:

  • Developed statistical methods and software in genetic association analysis controlling population stratification and rare variants association analysis. He and his colleagues have developed methods to identify rare variants contributing to phenotypic variations using unrelated and family data. 
  • Developed admixture mapping methods and software in disease mapping using recent admixed population data, and performed the first admixture mapping analysis to search for genes underlying hypertension.
  • Identified genes contributing to variation in hypertension-related traits. 
  • Identified multiple genes and variants associated with obesity and sleep apnea related traits. Although the identified variants only explain a small amount of phenotype variation, they bring novel biological insight to the understanding of complex traits.

Professional Memberships

The American Society of Human Genetics
The International Genetic Epidemiology Society
Fellow, the Royal Statistical Society
Continental Origins and Genetic Epidemiology Network (COGENT) consortium

Publications

  1. Bai, WY, Wang, L, Ying, ZM, Hu, B, Xu, L, Zhang, GQ, Cong, PK, Zhu, X, Zou, W, Zheng, HF. Identification of PIEZO1 polymorphisms for human bone mineral density. Bone 2020; 133 : 115247. PubMed PMID:31968281 .
  2. Yan, T, Liang, J, Gao, J, Wang, L, Fujioka, H, Alzheimer Disease Neuroimaging Initiative, Zhu, X, Wang, X. FAM222A encodes a protein which accumulates in plaques in Alzheimer's disease. Nat Commun 2020; 11 (1): 411. PubMed PMID:31964863 PubMed Central PMC6972869.
  3. Wang, H, Sofer, T, Zhang, X, Elston, RC, Redline, S, Zhu, X. Local Ancestry Inference in Large Pedigrees. Sci Rep 2020; 10 (1): 189. PubMed PMID:31932708 PubMed Central PMC6957497.
  4. Noordam, R, Bos, MM, Wang, H, Winkler, TW, Bentley, AR, Kilpeläinen, TO, de Vries, PS, Sung, YJ, Schwander, K, Cade, BE, Manning, A, Aschard, H, Brown, MR, Chen, H, Franceschini, N, Musani, SK, Richard, M, Vojinovic, D, Aslibekyan, S, Bartz, TM, de Las Fuentes, L, Feitosa, M, Horimoto, AR, Ilkov, M, Kho, M, Kraja, A, Li, C, Lim, E, Liu, Y, Mook-Kanamori, DO, Rankinen, T, Tajuddin, SM, van der Spek, A, Wang, Z, Marten, J, Laville, V, Alver, M, Evangelou, E, Graff, ME, He, M, Kühnel, B, Lyytikäinen, LP, Marques-Vidal, P, Nolte, IM, Palmer, ND, Rauramaa, R, Shu, XO, Snieder, H, Weiss, S, Wen, W, Yanek, LR, Adolfo, C, Ballantyne, C, Bielak, L, Biermasz, NR, Boerwinkle, E, Dimou, N, Eiriksdottir, G, Gao, C, Gharib, SA, Gottlieb, DJ, Haba-Rubio, J, Harris, TB, Heikkinen, S, Heinzer, R, Hixson, JE, Homuth, G, Ikram, MA, Komulainen, P, Krieger, JE, Lee, J, Liu, J, Lohman, KK, Luik, AI, Mägi, R, Martin, LW, Meitinger, T, Metspalu, A, Milaneschi, Y, Nalls, MA, O'Connell, J, Peters, A, Peyser, P, Raitakari, OT, Reiner, AP, Rensen, PCN, Rice, TK, Rich, SS, Roenneberg, T, Rotter, JI, Schreiner, PJ, Shikany, J, Sidney, SS, Sims, M, Sitlani, CM, Sofer, T, Strauch, K, Swertz, MA, Taylor, KD, Uitterlinden, AG, van Duijn, CM, Völzke, H, Waldenberger, M, Wallance, RB, van Dijk, KW, Yu, C, Zonderman, AB, Becker, DM, Elliott, P, Esko, T, Gieger, C, Grabe, HJ, Lakka, TA, Lehtimäki, T, North, KE, Penninx, BWJH, Vollenweider, P, Wagenknecht, LE, Wu, T, Xiang, YB, Zheng, W, Arnett, DK, Bouchard, C, Evans, MK, Gudnason, V, Kardia, S, Kelly, TN, Kritchevsky, SB, Loos, RJF, Pereira, AC, Province, M, Psaty, BM, Rotimi, C, Zhu, X, Amin, N, Cupples, LA, Fornage, M, Fox, EF, Guo, X, Gauderman, WJ, Rice, K, Kooperberg, C, Munroe, PB, Liu, CT, Morrison, AC, Rao, DC, van Heemst, D, Redline, S. Multi-ancestry sleep-by-SNP interaction analysis in 126,926 individuals reveals lipid loci stratified by sleep duration. Nat Commun 2019; 10 (1): 5121. PubMed PMID:31719535 PubMed Central PMC6851116.
  5. Liang, J, Cade, BE, He, KY, Wang, H, Lee, J, Sofer, T, Williams, S, Li, R, Chen, H, Gottlieb, DJ, Evans, DS, Guo, X, Gharib, SA, Hale, L, Hillman, DR, Lutsey, PL, Mukherjee, S, Ochs-Balcom, HM, Palmer, LJ, Rhodes, J, Purcell, S, Patel, SR, Saxena, R, Stone, KL, Tang, W, Tranah, GJ, Boerwinkle, E, Lin, X, Liu, Y, Psaty, BM, Vasan, RS, Cho, MH, Manichaikul, A, Silverman, EK, Barr, RG, Rich, SS, Rotter, JI, Wilson, JG, NHLBI Trans-Omics for Precision Medicine (TOPMed), TOPMed Sleep Working Group, Redline, S, Zhu, X. Sequencing Analysis at 8p23 Identifies Multiple Rare Variants in DLC1 Associated with Sleep-Related Oxyhemoglobin Saturation Level. Am. J. Hum. Genet. 2019; 105 (5): 1057-1068. PubMed PMID:31668705 PubMed Central PMC6849112.
  6. Wang, H, Lane, JM, Jones, SE, Dashti, HS, Ollila, HM, Wood, AR, van Hees, VT, Brumpton, B, Winsvold, BS, Kantojärvi, K, Palviainen, T, Cade, BE, Sofer, T, Song, Y, Patel, K, Anderson, SG, Bechtold, DA, Bowden, J, Emsley, R, Kyle, SD, Little, MA, Loudon, AS, Scheer, FAJL, Purcell, SM, Richmond, RC, Spiegelhalder, K, Tyrrell, J, Zhu, X, Hublin, C, Kaprio, JA, Kristiansson, K, Sulkava, S, Paunio, T, Hveem, K, Nielsen, JB, Willer, CJ, Zwart, JA, Strand, LB, Frayling, TM, Ray, D, Lawlor, DA, Rutter, MK, Weedon, MN, Redline, S, Saxena, R. Genome-wide association analysis of self-reported daytime sleepiness identifies 42 loci that suggest biological subtypes. Nat Commun 2019; 10 (1): 3503. PubMed PMID:31409809 PubMed Central PMC6692391.
  7. Barfield, R, Wang, H, Liu, Y, Brody, JA, Swenson, B, Li, R, Bartz, TM, Sotoodehnia, N, Chen, YI, Cade, BE, Chen, H, Patel, SR, Zhu, X, Gharib, SA, Johnson, WC, Rotter, JI, Saxena, R, Purcell, S, Lin, X, Redline, S, Sofer, T. Epigenome-wide association analysis of daytime sleepiness in the Multi-Ethnic Study of Atherosclerosis reveals African-American-specific associations. Sleep 2019; 42 (8): . PubMed PMID:31139831 PubMed Central PMC6685317.
  8. Sung, YJ, de Las Fuentes, L, Winkler, TW, Chasman, DI, Bentley, AR, Kraja, AT, Ntalla, I, Warren, HR, Guo, X, Schwander, K, Manning, AK, Brown, MR, Aschard, H, Feitosa, MF, Franceschini, N, Lu, Y, Cheng, CY, Sim, X, Vojinovic, D, Marten, J, Musani, SK, Kilpeläinen, TO, Richard, MA, Aslibekyan, S, Bartz, TM, Dorajoo, R, Li, C, Liu, Y, Rankinen, T, Smith, AV, Tajuddin, SM, Tayo, BO, Zhao, W, Zhou, Y, Matoba, N, Sofer, T, Alver, M, Amini, M, Boissel, M, Chai, JF, Chen, X, Divers, J, Gandin, I, Gao, C, Giulianini, F, Goel, A, Harris, SE, Hartwig, FP, He, M, Horimoto, ARVR, Hsu, FC, Jackson, AU, Kammerer, CM, Kasturiratne, A, Komulainen, P, Kühnel, B, Leander, K, Lee, WJ, Lin, KH, Luan, J, Lyytikäinen, LP, McKenzie, CA, Nelson, CP, Noordam, R, Scott, RA, Sheu, WHH, Stančáková, A, Takeuchi, F, van der Most, PJ, Varga, TV, Waken, RJ, Wang, H, Wang, Y, Ware, EB, Weiss, S, Wen, W, Yanek, LR, Zhang, W, Zhao, JH, Afaq, S, Alfred, T, Amin, N, Arking, DE, Aung, T, Barr, RG, Bielak, LF, Boerwinkle, E, Bottinger, EP, Braund, PS, Brody, JA, Broeckel, U, Cade, B, Campbell, A, Canouil, M, Chakravarti, A, Cocca, M, Collins, FS, Connell, JM, de Mutsert, R, de Silva, HJ, Dörr, M, Duan, Q, Eaton, CB, Ehret, G, Evangelou, E, Faul, JD, Forouhi, NG, Franco, OH, Friedlander, Y, Gao, H, Gigante, B, Gu, CC, Gupta, P, Hagenaars, SP, Harris, TB, He, J, Heikkinen, S, Heng, CK, Hofman, A, Howard, BV, Hunt, SC, Irvin, MR, Jia, Y, Katsuya, T, Kaufman, J, Kerrison, ND, Khor, CC, Koh, WP, Koistinen, HA, Kooperberg, CB, Krieger, JE, Kubo, M, Kutalik, Z, Kuusisto, J, Lakka, TA, Langefeld, CD, Langenberg, C, Launer, LJ, Lee, JH, Lehne, B, Levy, D, Lewis, CE, Li, Y, Lifelines Cohort Study, Lim, SH, Liu, CT, Liu, J, Liu, J, Liu, Y, Loh, M, Lohman, KK, Louie, T, Mägi, R, Matsuda, K, Meitinger, T, Metspalu, A, Milani, L, Momozawa, Y, Mosley, TH Jr, Nalls, MA, Nasri, U, O'Connell, JR, Ogunniyi, A, Palmas, WR, Palmer, ND, Pankow, JS, Pedersen, NL, Peters, A, Peyser, PA, Polasek, O, Porteous, D, Raitakari, OT, Renström, F, Rice, TK, Ridker, PM, Robino, A, Robinson, JG, Rose, LM, Rudan, I, Sabanayagam, C, Salako, BL, Sandow, K, Schmidt, CO, Schreiner, PJ, Scott, WR, Sever, P, Sims, M, Sitlani, CM, Smith, BH, Smith, JA, Snieder, H, Starr, JM, Strauch, K, Tang, H, Taylor, KD, Teo, YY, Tham, YC, Uitterlinden, AG, Waldenberger, M, Wang, L, Wang, YX, Wei, WB, Wilson, G, Wojczynski, MK, Xiang, YB, Yao, J, Yuan, JM, Zonderman, AB, Becker, DM, Boehnke, M, Bowden, DW, Chambers, JC, Chen, YI, Weir, DR, de Faire, U, Deary, IJ, Esko, T, Farrall, M, Forrester, T, Freedman, BI, Froguel, P, Gasparini, P, Gieger, C, Horta, BL, Hung, YJ, Jonas, JB, Kato, N, Kooner, JS, Laakso, M, Lehtimäki, T, Liang, KW, Magnusson, PKE, Oldehinkel, AJ, Pereira, AC, Perls, T, Rauramaa, R, Redline, S, Rettig, R, Samani, NJ, Scott, J, Shu, XO, van der Harst, P, Wagenknecht, LE, Wareham, NJ, Watkins, H, Wickremasinghe, AR, Wu, T, Kamatani, Y, Laurie, CC, Bouchard, C, Cooper, RS, Evans, MK, Gudnason, V, Hixson, J, Kardia, SLR, Kritchevsky, SB, Psaty, BM, van Dam, RM, Arnett, DK, Mook-Kanamori, DO, Fornage, M, Fox, ER, Hayward, C, van Duijn, CM, Tai, ES, Wong, TY, Loos, RJF, Reiner, AP, Rotimi, CN, Bierut, LJ, Zhu, X, Cupples, LA, Province, MA, Rotter, JI, Franks, PW, Rice, K, Elliott, P, Caulfield, MJ, Gauderman, WJ, Munroe, PB, Rao, DC, Morrison, AC. A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure. Hum. Mol. Genet. 2019; : . PubMed PMID:31127295 PubMed Central PMC6644157.
  9. Cade, BE, Chen, H, Stilp, AM, Louie, T, Ancoli-Israel, S, Arens, R, Barfield, R, Below, JE, Cai, J, Conomos, MP, Evans, DS, Frazier-Wood, AC, Gharib, SA, Gleason, KJ, Gottlieb, DJ, Hillman, DR, Johnson, WC, Lederer, DJ, Lee, J, Loredo, JS, Mei, H, Mukherjee, S, Patel, SR, Post, WS, Purcell, SM, Ramos, AR, Reid, KJ, Rice, K, Shah, NA, Sofer, T, Taylor, KD, Thornton, TA, Wang, H, Yaffe, K, Zee, PC, Hanis, CL, Palmer, LJ, Rotter, JI, Stone, KL, Tranah, GJ, Wilson, JG, Sunyaev, SR, Laurie, CC, Zhu, X, Saxena, R, Lin, X, Redline, S. Associations of variants In the hexokinase 1 and interleukin 18 receptor regions with oxyhemoglobin saturation during sleep. PLoS Genet. 2019; 15 (4): e1007739. PubMed PMID:30990817 PubMed Central PMC6467367.
  10. Qin, H, Zhao, J, Zhu, X. Identifying Rare Variant Associations in Admixed Populations. Sci Rep 2019; 9 (1): 5458. PubMed PMID:30931973 PubMed Central PMC6443736.

Education

Ph.D.
Biostatistics, Epidemiology and Biostatistics
Case Western Reserve University
1998
M.S.
Statistics
University of Cincinnati
1994
M.S.
Mathematics
Peking University
1989
B.Sc.
Mathematics
Peking University
1986

Additional Information

Xiaofeng Zhu, PhD Biosketch

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Student and mentee totals, over CWRU career/full academic career:  

  • Master’s: 3   
  • PhD:  9/10
  • Post-doc:  11/12  
  • A sampling of CWRU PhD graduates and Post-docs’ current careers:  
    • Harvard University, Research Associate
    • Mayo Clinic, Research Associate
    • Biometrics and Biomarkers at Foundation, Senior Director
    • University of Minnesota, Assistant Professor 
    • Loyola University Chicago, Associate Professor
    • Moffitt Cancer Center, Assistant Professor
    • Vanderbilt University, Assistant Professor
    • NIH, Research Scientist
    • Tulane University
    • Key Bank