Andrew Thomas DeWan, PhD, MPH
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Research Summary
Professor DeWan seeks to understand how variation in the human genome contributes to complex human diseases. Using high-throughput technologies, he conducts genome-wide association studies to map disease susceptibility loci. His work also emphasizes the development of methods that improve the way in which this information is interpreted and utilized by disease researchers. He is also interested in the role that the interaction between genetic and environmental factors plays on disease susceptibility. His past work mapping disease genes has led to the discovery of susceptibility loci for age-related macular degeneration, non-syndromic hearing loss, renal function and myopia. Current projects include a genetic study of childhood asthma, a study of genetic susceptibility loci for sepsis in collaboration with investigators at the Norwegian University of Science and Technology; studies to identify genetic factors contributing to acute lymphoblastic leukemia and lung cancer; and studies develop novel methods for incorporating rare and imputed variants for mapping pleiotropic loci for complex traits that also leverages other types of omics data including gene expression and whole genome sequence data in collaboration with investigators at Columbia University Medical Center.
Specialized Terms: Genetic epidemiology; Statistical genetics; Asthma; Sepsis; leukemia; lung cancer; pleiotropy
Extensive Research Description
My overarching research mission is to understand how variation in the human genome contributes to complex human diseases. My work is centered around a diverse set of complex traits using a strategy of narrowly defined phenotypes and stratification by ancestry to reduce heterogeneity and increase statistical power as well as extending analytical methods to look at genetic interactions and pleiotropy.
My research leverages data from high-throughput genotyping and sequencing studies (both primary and secondary data analysis) to identify genetic variants associated with the phenotype of interest. Using a highly homogeneous set of cases and controls, my work identified an HTRA1promoter variant significantly associated with the wet form of age-related macular degeneration. Additional approaches to reducing phenotypic heterogeneity have led to mapping a suggestive association with a genetic marker in PDE11A for children with atopic asthma, a marker on chromosome 17q21.2 that significantly interacts with asthma to increase body mass index (BMI), and variants in TCFL2 and ERBB4 associated with BMI in Hispanics and African Americans, respectively. My work has recently expanded to include childhood cancer, with a leading role in a GWAS for childhood acute lymphoblastic leukemia (ALL) that identified two novel loci and included the largest sample of Hispanic cases to date. I am now leveraging this data to study genetic variants in microRNAs that are associated with ALL (funded through my R03) as well as a better understanding of the genetic risk factors for ALL in Hispanics, Asians and African Americans.
Building on the success of exome sequencing a single family with multiple asthmatics, I obtained R01 funding to recruit and conduct exome sequencing of approximately 250 nuclear families with multiple children with asthma with the goal of identify rare variants segregating with asthma. A family-based strategy for mapping rare variants has numerous power advantages over a population-based design including a potential for higher genetic load within families with multiple affected subjects, avoiding population stratification and reducing environmental effects through shared living. This represents a paradigm shift in association mapping, as this technique has been largely limited to unrelated case-control studies. Beyond the immediate scope of this project, the data and biological samples that were collected will be able to be utilized in future studies of asthma, including studies to look at the involvement of microRNAs in asthma and rare variants contributing to virus-induced asthma (F32 to L. Wang).
I am regularly sought out for my expertise in gene mapping studies and thus my work has made significant contributions in the application of advanced mapping methods to a host of other projects. Recent papers have utilized principal components analysis to identify subjects of Jewish ancestry and conduct an analysis of sixteen genetic variants for pancreatic cancer among this narrowly defined ancestral population; genome-wide imputation to identify variants in piRNAs associated with glioma; risk score analysis to identify multiple variants associated with bipolar disease; and meta-analyses of genetic variants associated with infectious diseases to summarize previous evidence for genetic associations with West Nile and Dengue diseases.
My statistical work is focused on extending methods to identify genetic interactions as well as loci exhibiting pleiotropy. Given the current number of single-nucleotide polymorphisms (SNPs) genotyped simultaneously in a GWAS, examining all SNP-SNP interactions becomes daunting and increasingly difficult to identify statistically significant and replicable results. I am working on developing analytical approaches for conducting multi-stage analyses to identify replicable interactions in genome-wide data. One strategy to reduce phenotypic heterogeneity is to analyze multiple correlated phenotypes jointly and look for pleiotropic loci and a recent paper from my group has summarized the statistical analysis techniques that can be utilized for different data types to identify cross phenotype associations and then dissect these findings to identify pleiotropy. These dissection approaches are being applied to a large dataset to look for pleiotropic loci for asthma and obesity and comparing the power of univariate and multivariate methods (F31 to Y. Salinas).
Moving forward, I am expanding this work to develop novel methods for incorporating rare and imputed variants for mapping pleiotropic loci that also leverages other types of omics data including gene expression and whole genome sequence data. Pleiotropy, although an important phenomenon in genetic etiology, has not been adequately studied and there are limited methods to detect pleiotropy for rare and imputed variants. My work will address this gap using a multi-prong approach of pleiotropic association testing, estimating tissue-specific disease heritability and detecting tissue-specific pleiotropy. This highly innovative work is supported by two NIH R01 grants. Not only does the study of pleiotropic loci improve our understanding of the genetic etiology for complex diseases and traits, but it also has high public health significance; pleiotropic effects will improve our ability to estimate genetic risk and provide insight into drug targets for the development of treatments for multiple diseases due to shared genetic architecture.
One major challenge in genetic epidemiology is to identify additional risk loci that may have smaller effect sizes, affect multiple phenotypes, and/or non-additive effects. Through the genetic analyses of various phenotypes, models and diverse ancestral populations, and in concert with other omics data and clinical investigations, we will gain a better understanding of the genetic architecture of complex traits and begin to build the foundation for incorporating personalized medicine into clinical practice. My work will continue to make significant contributions to this goal.
Coauthors
Research Interests
Asthma; Chronic Disease; Epidemiology; Genetics; Leukemia; Norway; Pre-Eclampsia; Sepsis; Biostatistics; Genetic Pleiotropy
Public Health Interests
Cancer; Genetics, Genomics, Epigenetics; Infectious Diseases; Pollution
Selected Publications
- Inferring feature importance with uncertainties with application to large genotype dataJohnsen P, Strümke I, Langaas M, DeWan A, Riemer-Sørensen S. Inferring feature importance with uncertainties with application to large genotype data PLOS Computational Biology 2023, 19: e1010963. PMID: 36917581, PMCID: PMC10038287, DOI: 10.1371/journal.pcbi.1010963.
- Early-Onset Colorectal Cancer Somatic Gene Mutations by Population Subgroups.Shen X, DeWan A, Johnson C. Early-Onset Colorectal Cancer Somatic Gene Mutations by Population Subgroups. Cancer Discovery 2023, 13: 530-531. PMID: 36855917, DOI: 10.1158/2159-8290.cd-22-1464.
- The genetic contribution of the X chromosome in age-related hearing lossNaderi E, Cornejo-Sanchez D, Li G, Schrauwen I, Wang G, Dewan A, Leal S. The genetic contribution of the X chromosome in age-related hearing loss Frontiers In Genetics 2023, 14: 1106328. PMID: 36896235, PMCID: PMC9988903, DOI: 10.3389/fgene.2023.1106328.
- Rare-variant association analysis reveals known and new age-related hearing loss genesCornejo-Sanchez D, Li G, Fabiha T, Wang R, Acharya A, Everard J, Kadlubowska M, Huang Y, Schrauwen I, Wang G, DeWan A, Leal S. Rare-variant association analysis reveals known and new age-related hearing loss genes European Journal Of Human Genetics 2023, 31: 638-647. PMID: 36788145, PMCID: PMC10250305, DOI: 10.1038/s41431-023-01302-2.
- Type 2 cytokine genes as allergic asthma risk factors after viral bronchiolitis in early childhoodDong Z, Myklebust Å, Johnsen I, Jartti T, Døllner H, Risnes K, DeWan A. Type 2 cytokine genes as allergic asthma risk factors after viral bronchiolitis in early childhood Frontiers In Immunology 2023, 13: 1054119. DOI: 10.3389/fimmu.2022.1054119.
- Type 2 cytokine genes as allergic asthma risk factors after viral bronchiolitis in early childhoodDong Z, Myklebust Å, Johnsen I, Jartti T, Døllner H, Risnes K, DeWan A. Type 2 cytokine genes as allergic asthma risk factors after viral bronchiolitis in early childhood Frontiers In Immunology 2023, 13: 1054119. PMID: 36685501, PMCID: PMC9852873, DOI: 10.3389/fimmu.2022.1054119.
- Circulating miRNAs in the first trimester and pregnancy complications: a systematic reviewSubramanian A, Weiss D, Nyhan K, Dewan A, Jukic A. Circulating miRNAs in the first trimester and pregnancy complications: a systematic review Epigenetics 2022, 18: 2152615. PMID: 36503407, PMCID: PMC9980650, DOI: 10.1080/15592294.2022.2152615.
- Escalation of Antithrombotic Therapy in Patients With Premature Peripheral Artery Disease Undergoing Lower Extremity RevascularizationKim T, DeWan A, Murray M, Wang H, Mani A, Mena-Hurtado C, Guzman R, Chaar C. Escalation of Antithrombotic Therapy in Patients With Premature Peripheral Artery Disease Undergoing Lower Extremity Revascularization Journal Of Vascular Surgery 2022, 75: e281. DOI: 10.1016/j.jvs.2022.03.640.
- Lower Extremity Revascularization Among Patients With Premature Peripheral Artery Disease Compared To Patients At The Common Age Of Presentation In The Vascular Quality InitiativeKim T, Loh S, Dewan A, Murray M, Mojibian H, Mani A, Mena-Hurtado C, Chaar C. Lower Extremity Revascularization Among Patients With Premature Peripheral Artery Disease Compared To Patients At The Common Age Of Presentation In The Vascular Quality Initiative Annals Of Vascular Surgery 2022, 79: 400-401. DOI: 10.1016/j.avsg.2021.12.049.
- Rates of Neuropsychiatric Disorders and Gestational Age at Birth in a Danish PopulationXia Y, Xiao J, Yu Y, Tseng W, Lebowitz E, DeWan A, Pedersen L, Olsen J, Li J, Liew Z. Rates of Neuropsychiatric Disorders and Gestational Age at Birth in a Danish Population Obstetrical & Gynecological Survey 2021, 76: 719-721. DOI: 10.1097/01.ogx.0000802660.47978.73.
- Abstract PS8-17: Assessing effect modification of obesity-associated genes variants in FTO , MC4R , BDNF , and CREB1 on weight loss among breast cancer survivors enrolled in the randomized lifestyle, exercise, and nutrition (LEAN) studyNguyen T, Irwin M, Dewan A, Harrigan M, Cartmel B, Sanft T, Lu L, Li F, Salinas Y. Abstract PS8-17: Assessing effect modification of obesity-associated genes variants in FTO , MC4R , BDNF , and CREB1 on weight loss among breast cancer survivors enrolled in the randomized lifestyle, exercise, and nutrition (LEAN) study Cancer Research 2021, 81: ps8-17-ps8-17. DOI: 10.1158/1538-7445.sabcs20-ps8-17.
- Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization studyRogne T, Solligård E, Burgess S, Brumpton BM, Paulsen J, Prescott HC, Mohus RM, Gustad LT, Mehl A, Åsvold BO, DeWan AT, Damås JK. Body mass index and risk of dying from a bloodstream infection: A Mendelian randomization study PLOS Medicine 2020, 17: e1003413. PMID: 33196656, PMCID: PMC7668585, DOI: 10.1371/journal.pmed.1003413.
- Genetic Determinants of Blood Cell Traits Play a Role in Susceptibility to Acute Lymphoblastic LeukemiaKachuri L, Jeon S, DeWan A, Metayer C, Witte J, Ma X, Chiang C, Wiemels J, de Smith A. Genetic Determinants of Blood Cell Traits Play a Role in Susceptibility to Acute Lymphoblastic Leukemia Blood 2020, 136: 10-11. DOI: 10.1182/blood-2020-141443.
- Discovery and Mediation Analysis of Cross-Phenotype Associations Between Asthma and Body Mass Index in 12q13.2Salinas YD, Wang Z, DeWan AT. Discovery and Mediation Analysis of Cross-Phenotype Associations Between Asthma and Body Mass Index in 12q13.2 American Journal Of Epidemiology 2020, 190: 85-94. PMID: 32700739, PMCID: PMC7784522, DOI: 10.1093/aje/kwaa144.
- The Role of FER rs4957796 in Risk of Developing and Dying from a Bloodstream Infection: A 23-Year Follow-Up of the Population-Based HUNT StudyRogne T, Damås JK, Flatby HM, Åsvold BO, DeWan AT, Solligård E. The Role of FER rs4957796 in Risk of Developing and Dying from a Bloodstream Infection: A 23-Year Follow-Up of the Population-Based HUNT Study Clinical Infectious Diseases 2020, 73: ciaa786-. PMID: 32699877, PMCID: PMC8282309, DOI: 10.1093/cid/ciaa786.
- Abstract IA38: What causes the increased risk of acute lymphoblastic leukemia in Latinos?de Smith A, Feng Q, Walsh K, Jeon S, Morimoto L, DeWan A, Chiang C, Metayer C, Ma X, Wiemels J. Abstract IA38: What causes the increased risk of acute lymphoblastic leukemia in Latinos? Cancer Epidemiology Biomarkers & Prevention 2020, 29: ia38-ia38. DOI: 10.1158/1538-7755.disp19-ia38.
- MendelProb: probability and sample size calculations for Mendelian studies of exome and whole genome sequence dataHe Z, Wang L, DeWan A, Leal S. MendelProb: probability and sample size calculations for Mendelian studies of exome and whole genome sequence data Bioinformatics 2018, 35: 529-531. PMID: 30032240, PMCID: PMC6397596, DOI: 10.1093/bioinformatics/bty542.
- Family‐based study reveals decreased abundance of sputum Granulicatella in asthmaticsWang L, Solá D, Mao Y, Bielecki P, Zhu Y, Sun Z, Shan L, Flavell R, Bazzy‐Asaad A, DeWan A. Family‐based study reveals decreased abundance of sputum Granulicatella in asthmatics Allergy 2018, 73: 1918-1921. PMID: 29862523, PMCID: PMC6586473, DOI: 10.1111/all.13493.
- Gene-Gene and Gene-Environment InteractionsDeWan AT. Gene-Gene and Gene-Environment Interactions 2018, 1793: 89-110. PMID: 29876893, DOI: 10.1007/978-1-4939-7868-7_7.
- GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21Wiemels JL, Walsh KM, de Smith AJ, Metayer C, Gonseth S, Hansen HM, Francis SS, Ojha J, Smirnov I, Barcellos L, Xiao X, Morimoto L, McKean-Cowdin R, Wang R, Yu H, Hoh J, DeWan AT, Ma X. GWAS in childhood acute lymphoblastic leukemia reveals novel genetic associations at chromosomes 17q12 and 8q24.21 Nature Communications 2018, 9: 286. PMID: 29348612, PMCID: PMC5773513, DOI: 10.1038/s41467-017-02596-9.
- Statistical Analysis of Multiple Phenotypes in Genetic Epidemiologic Studies: From Cross-Phenotype Associations to Pleiotropy.Salinas YD, Wang Z, DeWan AT. Statistical Analysis of Multiple Phenotypes in Genetic Epidemiologic Studies: From Cross-Phenotype Associations to Pleiotropy. American Journal Of Epidemiology 2017, 187: 855-863. PMID: 29020254, PMCID: PMC5889027, DOI: 10.1093/aje/kwx296.
- Abstract 1326: A pooled genome-wide association study of pancreatic cancer susceptibility loci in American JewsStreicher S, Klein A, Olson S, Kurtz R, DeWan A, Zhao H, Risch H. Abstract 1326: A pooled genome-wide association study of pancreatic cancer susceptibility loci in American Jews Cancer Research 2017, 77: 1326-1326. DOI: 10.1158/1538-7445.am2017-1326.
- Multiethnic genome-wide association study identifies ethnic-specific associations with body mass index in Hispanics and African AmericansSalinas YD, Wang L, DeWan AT. Multiethnic genome-wide association study identifies ethnic-specific associations with body mass index in Hispanics and African Americans BMC Genomic Data 2016, 17: 78. PMID: 27296613, PMCID: PMC4907283, DOI: 10.1186/s12863-016-0387-0.
- ZNF248 Is Associated with Elder-Onset Asthma in African AmericansWang L, Salinas Y, DeWan A. ZNF248 Is Associated with Elder-Onset Asthma in African Americans Journal Of Allergy And Clinical Immunology 2016, 137: ab104. DOI: 10.1016/j.jaci.2015.12.467.
- Predictors of tanning dependence in white non-hispanic females and malesCartmel B, Mayne S, Bale A, Gelernter J, DeWan A, Leffell D, Pagoto S, Spain P, Ferrucci L. Predictors of tanning dependence in white non-hispanic females and males Dermatology Online Journal 2016, 22 DOI: 10.5070/d3229032556.
- Abstract 4623: piRNA and glioma risk: Evidence from a post-GWAS analysis of the GliomaScan CohortJacobs D, Lerro M, Fu A, Qin Q, DeWan A, Dubrow R, Claus E, Zhu Y. Abstract 4623: piRNA and glioma risk: Evidence from a post-GWAS analysis of the GliomaScan Cohort 2015, 4623-4623. DOI: 10.1158/1538-7445.am2015-4623.
- Confronting the missing epistasis problem: on the reproducibility of gene–gene interactionsMurk W, Bracken MB, DeWan AT. Confronting the missing epistasis problem: on the reproducibility of gene–gene interactions Human Genetics 2015, 134: 837-849. PMID: 25998948, DOI: 10.1007/s00439-015-1564-3.
- Functional Variants of the Lepr Gene in Patients With HyperparathyroidismSue G, Hoang D, Li A, Pizzoforato N, Sosa J, Roman S, Dewan A, Narayan D. Functional Variants of the Lepr Gene in Patients With Hyperparathyroidism Journal Of Surgical Research 2013, 179: 247. DOI: 10.1016/j.jss.2012.10.463.
- Whole-exome sequencing of a pedigree segregating asthmaDeWan AT, Egan KB, Hellenbrand K, Sorrentino K, Pizzoferrato N, Walsh KM, Bracken MB. Whole-exome sequencing of a pedigree segregating asthma BMC Medical Genomics 2012, 13: 95. PMID: 23046476, PMCID: PMC3563469, DOI: 10.1186/1471-2350-13-95.
- A novel bioinformatics approach for identifying the genetic contributions to preeclampsiaUzun A, Dewan A, Triche E, Kurihara S, Laliberte A, Padbury J. A novel bioinformatics approach for identifying the genetic contributions to preeclampsia Journal Of Reproductive Immunology 2012, 94: 121-122. DOI: 10.1016/j.jri.2012.03.471.
- PDE11A associations with asthma: Results of a genome-wide association scanDeWan AT, Triche EW, Xu X, Hsu LI, Zhao C, Belanger K, Hellenbrand K, Willis-Owen SA, Moffatt M, Cookson WO, Himes BE, Weiss ST, Gauderman WJ, Baurley JW, Gilliland F, Wilk JB, O’Connor G, Strachan DP, Hoh J, Bracken MB. PDE11A associations with asthma: Results of a genome-wide association scan Journal Of Allergy And Clinical Immunology 2010, 126: 871-873.e9. PMID: 20920776, PMCID: PMC3133448, DOI: 10.1016/j.jaci.2010.06.051.
- Detecting essential and removable interactions in genome-wide association studies.Dewan A, Dubrow R, Hoh J, Liu X, Wu C, Yang Y, Ying Z, Zhang H. Detecting essential and removable interactions in genome-wide association studies. Statistics And Its Interface 2009, 2: 161-170. PMID: 21165165, PMCID: PMC3002050, DOI: 10.4310/sii.2009.v2.n2.a6.
- Linkage Disequilibrium Mapping for Complex Disease GenesDeWan A, Klein R, Hoh J. Linkage Disequilibrium Mapping for Complex Disease Genes 2007, 376: 85-108. DOI: 10.1385/1-59745-389-7:85.
- HTRA1 promoter polymorphism in wet age-related macular degenerationDeWan A, Liu M, Hartman S, Zhang S, Liu D, Zhao C, Tam P, Chan W, Lam D, Snyder M, Barnstable C, Pang C, Hoh J. HTRA1 promoter polymorphism in wet age-related macular degeneration American Journal Of Ophthalmology 2007, 143: 376. DOI: 10.1016/j.ajo.2006.12.017.
- HTRA1 Promoter Polymorphism in Wet Age-Related Macular DegenerationDeWan A, Liu M, Hartman S, Zhang SS, Liu DT, Zhao C, Tam PO, Chan WM, Lam DS, Snyder M, Barnstable C, Pang CP, Hoh J. HTRA1 Promoter Polymorphism in Wet Age-Related Macular Degeneration Science 2006, 314: 989-992. PMID: 17053108, DOI: 10.1126/science.1133807.
- A second kindred linked to DFNA20 (17q25.3) reduces the genetic intervalDeWan A, Parrado A, Leal S. A second kindred linked to DFNA20 (17q25.3) reduces the genetic interval Clinical Genetics 2002, 63: 39-45. PMID: 12519370, PMCID: PMC6143177, DOI: 10.1034/j.1399-0004.2003.630106.x.
- Linkage of Left Ventricular Contractility to Chromosome 11 in HumansArnett D, Devereux R, Kitzman D, Oberman A, Hopkins P, Atwood L, Dewan A, Rao DC. Linkage of Left Ventricular Contractility to Chromosome 11 in Humans Hypertension 2001, 38: 767-772. PMID: 11641284, DOI: 10.1161/hy1001.092650.
- A Genome Scan for Renal Function among Hypertensives: the HyperGEN StudyDeWan A, Arnett D, Atwood L, Province M, Lewis C, Hunt S, Eckfeldt J. A Genome Scan for Renal Function among Hypertensives: the HyperGEN Study American Journal Of Human Genetics 2000, 68: 136-144. PMID: 11115379, PMCID: PMC1234906, DOI: 10.1086/316927.
- Evidence for genetic heterogeneity in families with congenital motor nystagmus (CN)Oetting W, Armstrong C, Holleschau A, DeWan A, Summers C. Evidence for genetic heterogeneity in families with congenital motor nystagmus (CN) Ophthalmic Genetics 2000, 21: 227-233. DOI: 10.1076/1381-6810(200012)2141-hft227.