Genome-wide, whole genome sequence and integrative molecular omics analysis in multi-ancestry human cohort studies
Genome-wide, whole genome sequence and integrative molecular omics analysis in multi-ancestry human cohort studies
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Among many of our current efforts, we work actively analyzing large-scale data from the Multi-Ethnic Study of Atherosclerosis (MESA), performing genetic analyses and integration with molecular-omics data to identify molecular mechanisms underlying GWAS traits. Our work in this area is focused primarily on pulmonary (emphysema, lung function, COPD, ILD), heart failure, and cardiovascular disease. We also contribute actively to collaborative genetic analyses carried out through the CHARGE consortium and the Trans-Omics for Precision Medicine (TOPMed) effort.
a. Debban CL, Ambalavanan A, Ghosh A, Li Z, Buschur KL, Ma Y, George E, Pistenmaa C, Bertoni AG, Oelsner EC, Michos ED, Moraes TJ, Jacobs DR Jr, Christenson S, Bhatt SP, Kaner RJ, Simons E, Turvey SE, Vameghestahbanati M, Engert JC, Kirby M, Bourbeau J, Tan WC, Gabriel SB, Gupta N, Woodruff PG, Subbarao P, Ortega VE, Bleecker ER, Meyers DA, Rich SS, Hoffman EA, Barr RG, Cho MH, Bossé Y, Duan Q, Manichaikul A, Smith BM.. Am J Respir Crit Care Med. 2024 Dec 15;210(12):1421-1431. PMCID: 11716030.
b. Yang C, Veenstra J, Bartz TM, Pahl MC, Hallmark B, Chen YI, Westra J, Steffen LM, Brown CD, Siscovick D, Tsai MY, Wood AC, Rich SS, Smith CE, O'Connor TD, Mozaffarian D, Grant SFA, Chilton FH, Tintle NL, Lemaitre RN, Manichaikul A. Genome-wide association studies and fine-mapping identify genomic loci for n-3 and n-6 polyunsaturated fatty acids in Hispanic American and African American cohorts. Commun Biol. 2023 Aug 16;6(1):852. PMCID: 10432561.
c. Zhao X, Qiao D, Yang C, Kasela S, Kim W, Ma Y, …, Burkart KM, Kaplan RC, Wain LV, Tobin MD, London SJ, Lappalainen T, Oelsner EC, Abecasis GR, Silverman EK, Barr RG; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; TOPMed Lung Working Group, Cho MH, Manichaikul A. Whole genome sequence analysis of pulmonary function and COPD in 19,996 multi-ethnic participants. Nat Commun. 2020 Oct 14;11(1):5182. PMCID: 7598941.
Statistical methods and quality control for genetic and integrative molecular omics analysis in human studies
Statistical methods and quality control for genetic and integrative molecular omics analysis in human studies
Our group works on quality control of genetic and molecular ‘omics data in human studies. For example, we have played a central role in the quality control of genome-wide genotype and methylation data, as well as population structure analysis for the Multi-Ethnic Study of Atherosclerosis (MESA). We have also contributed toward method development efforts to integrate RNA-seq data with whole genome sequence for improved genetic risk prediction.
a. Hu X, Qiao D, Kim W, Moll M, Balte PP, Lange LA, Bartz TM, Kumar R, Li X, Yu B, Cade BE, Laurie CA, Sofer T, Ruczinski I, Nickerson DA, Muzny DM, Metcalf GA, Doddapaneni H, Gabriel S, Gupta N, Dugan-Perez S, Cupples LA, Loehr LR, Jain D, Rotter JI, Wilson JG, Psaty BM, Fornage M, Morrison AC, Vasan RS, Washko G, Rich SS, O'Connor GT, Bleecker E, Kaplan RC, Kalhan R, Redline S, Gharib SA, Meyers D, Ortega V, Dupuis J, London SJ, Lappalainen T, Oelsner EC, Silverman EK, Barr RG, Thornton TA, Wheeler HE; TOPMed Lung Working Group; Cho MH, Im HK, Manichaikul A. Polygenic transcriptome risk scores for COPD and lung function improve cross-ethnic portability of prediction in the NHLBI TOPMed program. Am J Hum Genet. 2022 May 5;109(5):857-870. PMCID: 9118106.
b. Liang Y, Pividori M, Manichaikul A, Palmer AA, Cox NJ, Wheeler H, Im HK. Polygenic transcriptome risk scores (PTRS) can improve portability of polygenic risk scores across ancestries. Genome Biol. 2022 Jan 13;23(1):23. PMCID: 8759285.
c. Manichaikul A, Palmas W, Rodriguez CJ, Peralta CA, Divers J, Guo X, Chen WM, Wong Q, Williams K, Kerr KF, Taylor KD, Tsai MY, Goodarzi MO, Sale MM, Diez-Roux AV, Rich SS, Rotter JI, Mychaleckyj JC. Population structure of Hispanics in the United States: the Multi-Ethnic Study of Atherosclerosis. PLoS Genet. 2012;8(4):e1002640. PMCID: 3325201.
Translational studies of candidate gene regions
Translational studies of candidate gene regions
We work on translational genetics focused on selected candidate genes identified based on Mendelian disease genes, experimental animal studies, or other approaches. We perform candidate gene and candidate variant studies to characterize genomic regions of interest at a greater level of detail than typically found from GWAS. We collaborate with numerous investigators to perform studies focused on specific candidate genes from animal models in order to determine whether or not these candidate genes show similar effects in humans within the context of genetic epidemiology.
a. Kim JS, Manichaikul AW, Hoffman EA, Balte P, Anderson MR, Bernstein EJ, Madahar P, Oelsner EC, Kawut SM, Wysoczanski A, Laine AF, Adegunsoye A, Ma JZ, Taub MA, Mathias RA, Rich SS, Rotter JI, Noth I, Garcia CK, Barr RG, Podolanczuk AJ. Thorax. 2023 Jun;78(6):566-573. PMCID: 9899287.
b. Yang C, Hallmark B, Chai JC, O'Connor TD, Reynolds LM, Wood AC, Seeds M, Chen YI, Steffen LM, Tsai MY, Kaplan RC, Daviglus ML, Mandarino LJ, Fretts AM, Lemaitre RN, Coletta DK, Blomquist SA, Johnstone LM, Tontsch C, Qi Q, Ruczinski I, Rich SS, Mathias RA, Chilton FH, Manichaikul A. Impact of Amerind ancestry and FADS genetic variation on omega-3 deficiency and cardiometabolic traits in Hispanic populations. Commun Biol. 2021 Jul 28;4(1):918. PMCID: 8319323.
c. Grant DJ, Manichaikul A, Alberg AJ, Bandera EV, Barnholtz-Sloan J, Bondy M, Cote ML, Funkhouser E, Moorman PG, Peres LC, …, Kelemen LE, Pharoah PDP, Song H, Campbell I, Eccles D, DeFazio A, Kennedy CJ, Schildkraut JM. Evaluation of vitamin D biosynthesis and pathway target genes reveals UGT2A1/2 and EGFR polymorphisms associated with epithelial ovarian cancer in African American Women. Cancer Med. 2019 May;8(5):2503-2513. PMCID: 6536963.
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