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Dr Anna Ulrich


Research Fellow

Academic and research departments

School of Biosciences and Medicine.

My publications

Publications

ANNA ULRICH, Pablo Otero-Núñez, John Wharton, Emilia M Swietlik, Stefan Gräf, N Morrell, D Wang, Allan Lawrie, Martin R Wilkins, Christopher J Rhodes (2020)Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension, In: Genes11(11)1247 MDPI

Expression quantitative trait loci (eQTL) can provide a link between disease susceptibility variants discovered by genetic association studies and biology. To date, eQTL mapping studies have been primarily conducted in healthy individuals from population-based cohorts. Genetic effects have been known to be context-specific and vary with changing environmental stimuli. We conducted a transcriptome- and genome-wide eQTL mapping study in a cohort of patients with idiopathic or heritable pulmonary arterial hypertension (PAH) using RNA sequencing (RNAseq) data from whole blood. We sought confirmation from three published population-based eQTL studies, including the GTEx Project, and followed up potentially novel eQTL not observed in the general population. In total, we identified 2314 eQTL of which 90% were cis-acting and 75% were confirmed by at least one of the published studies. While we observed a higher GWAS trait colocalization rate among confirmed eQTL, colocalisation rate of novel eQTL reported for lung-related phenotypes was twice as high as that of confirmed eQTL. Functional enrichment analysis of genes with novel eQTL in PAH highlighted immune-related processes, a suspected contributor to PAH. These potentially novel eQTL specific to or active in PAH could be useful in understanding genetic risk factors for other diseases that share common mechanisms with PAH.

James Dooley, V Lagou, Jermaine Goveia, ANNA ULRICH, Katerina Rohlenova, Nathalie Heirman, Tobias Karakach, Yulia Lampi, Shawez Khan, Jun Wang, Tom Dresselaers, Uwe Himmelreich, Marc J Gunter, P Carmeliet, AJ Liston (2020)Heterogeneous Effects of Calorie Content and Nutritional Components Underlie Dietary Influence on Pancreatic Cancer Susceptibility, In: Cell Reports32(2)107880 Cell Press

Pancreatic cancer is a rare but fatal form of cancer, the fourth highest in absolute mortality. Known risk factors include obesity, diet, and type 2 diabetes; however, the low incidence rate and interconnection of these factors confound the isolation of individual effects. Here, we use epidemiological analysis of prospective human cohorts and parallel tracking of pancreatic cancer in mice to dissect the effects of obesity, diet, and diabetes on pancreatic cancer. Through longitudinal monitoring and multi-omics analysis in mice, we found distinct effects of protein, sugar, and fat dietary components, with dietary sugars increasing Mad2l1 expression and tumor proliferation. Using epidemiological approaches in humans, we find that dietary sugars give a MAD2L1 genotype-dependent increased susceptibility to pancreatic cancer. The translation of these results to a clinical setting could aid in the identification of the at-risk population for screening and potentially harness dietary modification as a therapeutic measure. [Display omitted] •Distinct roles for dietary fat, protein, and sugar on murine pancreatic cancer•Dietary glucose triggers Mad2l1 upregulation and tumor cell proliferation in mice•Gene-diet interaction identifies sugar-MAD2L1 link in human pancreatic cancer•Dietary plant fats were protective in human pancreatic cancer susceptibility Dooley et al. used parallel analysis of a murine pancreatic cancer model and a human prospective cohort to study the interaction of diet and pancreatic cancer. Both systems identify complex effects with different dietary components, converging on a link between dietary sugar and the cell-cycle checkpoint gene MAD2L1.

V Lagou, Reedik Magi, JJ Hottenga, Harald Grallert, John R. Perry, Nabila Bouatia-Naji, Letizia Marullo, Denis Rybin, R Jansen, JL Min, AS Dimas, ANNA ULRICH, LIUDMILA ZUDINA, Jesper R Gådin, Longda Jiang, Alessia Faggian, Amélie Bonnefond, Joao Fadista, Maria G Stathopoulou, Aaron Isaacs, SM Willems, Pau Navarro, T Tanaka, Anne U Jackson, May E Montasser, Jeff R O'Connell, Lawrence F Bielak, R. Webster, Richa Saxena, Jeanette M Stafford, Beate St Pourcain, Nicholas J. Timpson, Perttu Salo, SY Shin, Najaf Amin, Albert V Smith, Guo Li, Niek Verweij, Anuj Goel, Ian Ford, Paul C D Johnson, T Johnson, Karen Kapur, G Thorleifsson, RJ Strawbridge, Laura J Rasmussen-Torvik, Tõnu Esko, Evelin Mihailov, T Fall, Ross M Fraser, A Mahajan, Stavroula Kanoni, Vilmantas Giedraitis, ME Kleber, Günther Silbernagel, Julia Meyer, Martina Müller-Nurasyid, Andrea Ganna, Antti-Pekka Sarin, Loic Yengo, Dmitry Shungin, J Luan, Momoko Horikoshi, Ping An, S Sanna, Yvonne Boettcher, NW Rayner, Ilja M Nolte, Tatijana Zemunik, Erik van Iperen, Peter Kovacs, Nicholas D Hastie, SH Wild, Stela McLachlan, SS Campbell, Ozren Polasek, Olga Carlson, Josephine Egan, Wieland Kiess, G Willemsen, Johanna Kuusisto, Markku Laakso, Maria Dimitriou, A Hicks, Rainer Rauramaa, S Bandinelli, B Thorand, Yongmei Liu, Iva Miljkovic, L Lind, Alex Doney, M Perola, AD Hingorani, M Kivimäki, Meena Kumari, Amanda J Bennett, C Groves, C Herder, Heikki A Koistinen, Leena Kinnunen, Ulf de Faire, Stephan J L Bakker, Matti Uusitupa, Colin N. A Palmer, J Wouter Jukema, N Sattar, A Pouta, H Snieder, E Boerwinkle, James S Pankow, PK Magnusson, Ulrika Krus, Chiara Scapoli, Eco J C N de Geus, Matthias Blüher, Bruce H R Wolffenbuttel, Michael A Province, G Abecasis, James B Meigs, G Kees Hovingh, Jaana Lindström, James F Wilson, Alan F Wright, GV Dedoussis, Stefan R Bornstein, Peter E H Schwarz, Anke Tönjes, BR Winkelmann, B Boehm, W März, Andres Metspalu, Jackie F Price, P Deloukas, Antje Körner, Timo A. Lakka, Sirkka M Keinanen-Kiukaanniemi, Timo E Saaristo, Richard N Bergman, J Tuomilehto, N Wareham, Claudia Langenberg, S Männistö, Paul Franks, C Hayward, Veronique Vitart, J Kaprio, Sophie Visvikis-Siest, Beverley Balkau, D Altshuler, Igor Rudan, Michael Stumvoll, Harry Campbell, Cornelia van Duijn, C Gieger, T Illig, L Ferrucci, NL Pedersen, Peter P Pramstaller, Michael Boehnke, Timothy M. Frayling, AR Shuldiner, Patricia A Peyser, Sharon L R Kardia, Lyle J. Palmer, BW Penninx, Pierre Meneton, T Harris, G Navis, Pim van der Harst, George Davey Smith, NG Forouhi, Ruth J F Loos, V Salomaa, N Soranzo, D Boomsma, Leif Groop, Tiinamaija Tuomi, Albert Hofman, Patricia B. Munroe, V Gudnason, DS Siscovick, H Watkins, Cecile Lecoeur, P Vollenweider, A Franco-Cereceda, P Eriksson, Marjo-Riitta Jarvelin, K Stefansson, A Hamsten, G Nicholson, Fredrik Karpe, ET Dermitzakis, C Lindgren, MI McCarthy, P Froguel, MARIKA KAAKINEN, VG Lyssenko, R Watanabe, E Ingelsson, Jose C Florez, J Dupuis, I Barroso, AP Morris, INGA PROKOPENKO (2021)Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability, In: Nature Communications1224 Nature Research

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.