Christopher D Brown, Ph.D.
415 Curie Blvd
Philadelphia, PA 19103
Lab: (215) 746-4049
University of Nebraska-Lincoln, 2001.
Stanford University, 2007.
Description of Research ExpertiseOur research focuses on how genotypes produce phenotypes and how they vary and evolve. We are particularly interested in identifying and experimentally characterizing functional human non-coding sequence variation. We aim to understand the mechanisms through which non-coding variants function, with an emphasis on understanding the mechanisms underlying complex human disease. We leverage a combination of high throughput experimental and computational approaches. We are currently focused on massively parallelizing assays that interrogate non-coding DNA function and applying these approaches to the fine-mapping of the causal variants underlying human disease.
Selected PublicationsThe GTEx Consortium, Battle A#, Brown CD#, Engelhardt BE#, Montgomery SM#: Genetic effects on gene expression across human tissues. Nature October 2017 Notes: This paper resulted from a large international consortium that I co-led. I directed cis-eQTL and GWAS analysis efforts and supervised over 20 trainees and analysts. Published in October, altmetric score 585, already cited 200 times.
Trizzino M#, Park Y, Holsbach-Beltrame M, Aracena K, Mika K, Caliskan M, Perry GH, Lynch VJ, Brown CD#: Transposable element exaptation is the primary source of novelty in the primate gene regulatory landscape. Genome Research October 2017 Notes: This paper describes data generated and analyses performed by two postdocs in my lab. We demonstrate that the vast majority of new primate cis-regulatory elements are derived from transposable element insertions. Published in October, altmetric score 150.
Pashos EE, Park Y, Wang X, Raghavan A, Yang W, Abbey D, Peters DT, Arbelaez J, Hernandez M, Kuperwasser N, Li W, Lian Z, Liu Y, Lv W, Lytle-Gabbin SL, Marchadier DH, Rogov P, Shi J, Slovik KJ, Stylianou IM, Wang L, Yan R, Zhang X, Kathiresan S, Duncan SA, Mikkelsen TS, Morrisey EE, Rader DJ#, Brown CD#, Musunuru K#: Large, Diverse Population Cohorts of hiPSCs and Derived Hepatocyte-like Cells Reveal Functional Genetic Variation at Blood Lipid-Associated Loci. Cell Stem Cell 20(4): 558, April 2017 Notes: This paper describes collaborative work with Kiran Musunuru and Dan Rader at Penn. My lab led iPSC, hepatocyte, and liver eQTL analyses and contributed to the integration of these data with publicly available blood lipid GWAS data.
Gallagher M, Posavi M, Huang P, Unger T, Berlyand Y, Gruenewald A, Chesi A, Manduchi E, Wells A, Grant S, Gerd Blobel G, Brown CD, Chen-Plotkin A: A dementia-associated risk variant near TMEM106B alters chromatin architecture and gene expression. American Journal of Human Genetics November 2017 Notes: This paper resulted from a collaboration with Alice Chen-Plotkin's lab at Penn. I performed eQTL analyses that demonstrated that TMEM106B is the likely causal gene underlying an FTD GWAS signal. I supervised the analysis of chromatin conformation capture data.
Kim HI, Raffler J, Lu W, Lee JJ, Abbey D, Saleheen D, Rabinowitz JD, Bennett MJ, Hand NJ, Brown CD, Rader DJ: Fine Mapping and Functional Analysis Reveal a Role of SLC22A1 in Acylcarnitine Transport. American Journal of Human Genetics October 2017 Notes: This describes collaborative work with Dan Rader at Penn. I advised on how to perform haplotype-level association analyses and I performed allele-specific expression analyses using data generated in my lab that supported SLC22A1 as the causative gene at a metabolite GWAS locus.
Ko YA, Yi H, Qiu C, Huang S, Park J, Ledo N, Köttgen A, Li H, Rader DJ, Pack MA, Brown CD, Susztak K: Genetic-Variation-Driven Gene-Expression Changes Highlight Genes with Important Functions for Kidney Disease. American Journal of Human Genetics 100(6): 940, June 2017 Notes: This paper describes collaborative work led by Katalin Susztak at Penn. I contributed to the design of the eQTL analyses and advised on the integration of these data with kidney disease GWAS data.
Khetarpal SA, Babb PL, Zhao W, Hancock-Cerutti WF, Brown CD, Rader DJ, Voight BF: Multiplexed targeted resequencing identifies coding and regulatory variation underlying phenotypic extremes of HDL-cholesterol in humans. Circ Genom Precis Med 11(7): e002070, July 2018 Notes: This manuscript describes work performed in collaboration with Ben Voight and Dan Rader at Penn. I contributed advice on the interpretation of human genetic and eQTL data.
Kember RL, Hou L, Ji X, Andersen LH, Ghorai A, Estrella LN, Almasy L, McMahon FJ, Brown CD, Bucan M: Genetic pleiotropy between mood disorders, metabolic, and endocrine traits in a multigenerational pedigree. Translational Psychiatry 8(1): doi.org/10.1038/s41398-018-0226-3, October 2018 Notes: This manuscript describes work from a long standing collaboration with Maja Bucan. I performed genotype phasing and imputation and contributed advice on the application and interpretation of polygenic risk scores.
Khetarpal SA, Schjoldager KT, Christoffersen C, Raghavan A, Edmondson AC, Reutter HM, Ahmed B, Ouazzani R, Peloso GM, Vitali C, Zhao W, Hanasoge Somasundara AM, Millar JS, Park Y, Fernando G, Livanov V, Choi S, Noé E, Patel P, Ho SP, Myocardial Infarction Exome Sequencing Study, Kirchgessner TG, Wandall HH, Hansen L, Bennett EP, Vakhrushev SY, Saleheen D, Kathiresan S, Brown CD, Jamra RA, LeGuern E, Clausen H, Rader DJ: Loss of Function of GALNT2 Lowers High-Density Lipoproteins in Humans, Nonhuman Primates, and Rodents. Cell Metabolism 24(2): 234-245, August 2016 Notes: This paper describes collaborative work with Dan Rader at Penn. I performed allele specific expression analyses using data generated in my lab. These analyses supported the causal role of GALNT2 at this HDL GWAS locus.
Ji X, Kember RL, Brown CD#, Bućan M#: Increased burden of deleterious variants in essential genes in autism spectrum disorder. Proceedings of the National Academy of Sciences 113(52): 201613195, December 2016 Notes: This paper describes collaborative work with Maja Bucan at Penn. I co-supervised the statistical analyses that demonstrated that essential genes harbor an increased load of deleterious mutations in autism cases.
Brown CD#, Mangravite LM, Engelhardt BE#: Integrative modeling of eQTLs and cis-regulatory elements suggests mechanisms underlying cell type specificity of eQTLs. PLoS Genetics 9(8): e1003649, August 2013 Notes: This paper describes collaborative work with Barbara Engelhardt. I performed eQTL meta analyses and eQTL/cis-regulatory element integration analyses that demonstrated that regulatory element activity is predictive of eQTL activity.