With my statistical and quantitative training backgrounds, I have multiple years of research experiences at the apolipoprotein (APOE) loci under the scopes of both epigenetics and genetics. I was the first to report the DNA methylation patterns at APOE loci in human primary peripheral CD4+ T cells across >900 free living human subjects, which was recently replicated by an independent UK biobank group (https://www.biorxiv.org/content/10.1101/815035v1). In addition, I have added some novel insights into the link between APOE and Alzheimer's disease (AD). Using the genome-wide association approach, I have identified 22 novel loci contributing to the risk of AD dementia stratified by APOE ?4 genotypes based on the whole exome sequencing data of the Alzheimer's disease sequencing project (ADSP). Based on the quantitative analysis of the DNA methylome and transcriptome of the primary human brain cortical tissues across multiple independent cohorts, I have found a potential factor to attenuate the risk effect of APOE ?4 on AD (under peer-review). For AD, APOE loci is considered as a high potency candidate for drug development where I am planning to fullfill my training packages for this effort.
1. Ma Y, Jun GR, Chung J, Zhang X, Kunkle BW, Naj AC, White CC, Bennett DA, De Jager PL, Mayeux R, Haines JL, Pericak-Vance MA, Schellenberg GD, Farrer LA, Lunetta KL. CpG-related SNPs in the MS4A region have a dose-dependent effect on risk of late-onset Alzheimer disease. Aging Cell. 2019 Aug;18(4):e12964. PubMed PMID: 31144443; PubMed Central PMCID: PMC6612647.
2. Ma Y, Jun GR, Zhang X, Chung J, Naj AC, Chen Y, Bellenguez C, Hamilton-Nelson K, Martin ER, Kunkle BW, Bis JC, Debette S, DeStefano AL, Fornage M, Nicolas G, van Duijn C, Bennett DA, De Jager PL, Mayeux R, Haines JL, Pericak-Vance MA, Seshadri S, Lambert JC, Schellenberg GD, Lunetta KL, Farrer LA. Analysis of Whole-Exome Sequencing Data for Alzheimer Disease Stratified by APOE Genotype. JAMA Neurol. 2019 Jun 10;PubMed PMID: 31180460; PubMed Central PMCID: PMC6563544.
3. Ma Y, Follis JL, Smith CE, Tanaka T, Manichaikul AW, Chu AY, Samieri C, Zhou X, Guan W, Wang L, Biggs ML, Chen YD, Hernandez DG, Borecki I, Chasman DI, Rich SS, Ferrucci L, Irvin MR, Aslibekyan S, Zhi D, Tiwari HK, Claas SA, Sha J, Kabagambe EK, Lai CQ, Parnell LD, Lee YC, Amouyel P, Lambert JC, Psaty BM, King IB, Mozaffarian D, McKnight B, Bandinelli S, Tsai MY, Ridker PM, Ding J, Mstat KL, Liu Y, Sotoodehnia N, Barberger-Gateau P, Steffen LM, Siscovick DS, Absher D, Arnett DK, Ordovás JM, Lemaitre RN. Interaction of methylation-related genetic variants with circulating fatty acids on plasma lipids: a meta-analysis of 7 studies and methylation analysis of 3 studies in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium. Am J Clin Nutr. 2016 Feb;103(2):567-78. PubMed PMID: 26791180; PubMed Central PMCID: PMC5260796.
4. Ma Y, Smith CE, Lai CQ, Irvin MR, Parnell LD, Lee YC, Pham L, Aslibekyan S, Claas SA, Tsai MY, Borecki IB, Kabagambe EK, Berciano S, Ordovás JM, Absher DM, Arnett DK. Genetic variants modify the effect of age on APOE methylation in the Genetics of Lipid Lowering Drugs and Diet Network study. Aging Cell. 2015 Feb;14(1):49-59. PubMed PMID: 25476875; PubMed Central PMCID: PMC4324456.