Stanulla, Martin
https://orcid.org/0000-0002-3834-0727
Mayo Clinic
University Hospitals Bristol NHS Foundation Trust
Citations 3
Design and quality control of large-scale two-sample Mendelian randomization studies
Haycock, Philip , Borges, Maria Carolina , Burrows, Kimberley , Harrison, Sean , Burgess, Stephen , Chang, Xuling , Khankari, Nikhil K. , Tsilidis, Kostas K, Gaunt, Tom R. , Hemani, Gibran , Zheng, Jie , Truong, Thérèse , Law, Matthew H. , Mariosa, Daniela , Hung, Rayjean J, Smith, George Davey , Relton, Caroline L. , Martin, Richard M. , Peters, Ulrike , Rice, Terri, Gallinger, Steve, Cornish, Alex J. , Vijayakrishnan, Jayaram , Wrensch, Margaret , Korat, Andres V Ardisson , Wheeler, Bill, Nilsson, Björn , Smith, Caren E. , Riadi, David, Claus, Elizabeth B. , Hosnijeh, Ng, Irene Oi‐Lin , Passow, Jeanette E, Han, Jiali , Schildkraut, Joellen M. , Wiemels, Joseph L. , Yang, Keming , Wu, Lang , Boutron, Marie-Christine, Iles, Mark M. , Stanulla, Martin , Gaudet, Mia M., Lenha, Mobuchon, Camp, Nicki J, Sham, Pak C. , Brennan, Paul , Jenkins, Robert B. , Diskin, Sharon J. , Berndt, Sonja I. , Tsavachidis, Spiridon, Channock, Stephen J., Galesloot, Tessel E. , Haycock, Philip , Harrison, Sean , Chang, Xuling , Zheng, Jie , Law, Matthew H , Birmann, Brenda M , Mariosa, Daniela , Zheng, Wei , Davey Smith, George , Borges, Maria C , Martin, Richard M , Iles, Mark M , Truong, Therese , Lemaître, Rozenn N. , Westra, Jason , Tsilidis, Kostas K, O’Mara, Tracy A. , Spurdle, Amanda B. , Slager, Susan L. , Birmann, Brenda M. , Hosnijeh, Fatemeh Saberi , Amos, Christopher I. , Hung, Rayjean J, Zheng, Wei , Gunter, Marc J. , Tintle, Nathan , Cheng, Iona C. , Jenkins, Mark A. , Sud, Amit , Johansson, Mattias , Norman, Aaron D. , Klein, Alison P. , Clay‐Gilmour, Alyssa , Franke, André , Heng, Chew‐Kiat , Song, Ci , Ellinghaus, Eva , Ostroumova, Evgenia , Vathaire, Florent de , Cugliari, Giovanni , Matullo, Giuseppe , Cerhan, James R. , Passow, Jeanette E. Eckel, Foo, Jia Nee , Liu, Jianjun , Barnholtz‐Sloan, Jill S. , Maris, John M. , Hemminki, Kari , Kiemeney, Lambertus A. , Ámundadóttir, Laufey T. , Stern, Marc‐Henri , Purdue, Mark P. , Bondy, Melissa L. , Guénel, Pascal , Taylor, Philip R. , Gharahkhani, Puya , Ostrom, Quinn T. , Stolzenberg‐Solomon, Rachael Z. , Dorajoo, Rajkumar , Houlston, Richard S. , Enroth, Stefan , Harrison, Tabitha A. , Gyllensten, Ulf B , Vijai, Joseph , Shi, Yufang , Yang, Wenjian , Lin, Yi , Van Den Eeden, Stephen K
International Journal of Epidemiology | February 11, 2023 | Volume: 52 | Issue: 5 | Pages: 1498-1521
Abstract Background Mendelian randomization (MR) studies are susceptible to metadata errors (e.g. incorrect specification of the effect allele column) and other analytical issues that can introduce substantial bias into analyses. We developed a quality control (QC) pipeline for the Fatty Acids in Cancer Mendelian Randomization Collaboration (FAMRC) that can be used to identify and correct for such errors. Methods We collated summary association statistics from fatty acid and cancer genome-wide association studies (GWAS) and subjected the collated data to a comprehensive QC pipeline. We identified metadata errors through comparison of study-specific statistics to external reference data sets (the National Human Genome Research Institute-European Bioinformatics Institute GWAS catalogue and 1000 genome super populations) and other analytical issues through comparison of reported to expected genetic effect sizes. Comparisons were based on three sets of genetic variants: (i) GWAS hits for fatty acids, (ii) GWAS hits for cancer and (iii) a 1000 genomes reference set. Results We collated summary data from 6 fatty acid and 54 cancer GWAS. Metadata errors and analytical issues with the potential to introduce substantial bias were identified in seven studies (11.6%). After resolving metadata errors and analytical issues, we created a data set of 219 842 genetic associations with 90 cancer types, generated in analyses of 566 665 cancer cases and 1 622 374 controls. Conclusions In this large MR collaboration, 11.6% of included studies were affected by a substantial metadata error or analytical issue. By increasing the integrity of collated summary data prior to their analysis, our protocol can be used to increase the reliability of downstream MR analyses. Our pipeline is available to other researchers via the CheckSumStats package (https://github.com/MRCIEU/CheckSumStats).
Genetic association with B-cell acute lymphoblastic leukemia in allogeneic transplant patients differs by age and sex
Clay‐Gilmour, Alyssa , Hahn, Theresa , Preus, Leah, Onel, Kenan , Skol, Andrew D. , Hungate, Eric A., Zhu, Qianqian , Haiman, Christopher A. , Pooler, Loreall , Sheng, Xin , Yan, Li , Liu, Qian , Liu, Song , Battaglia, Sebastiano , Zhu, Xiaochun , Block, AnneMarie W., Sait, Sheila N.J., Karaesmen, Ezgi , Rizvi, Abbas, Weisdorf, Daniel J. , Tritchler, David , Ellinghaus, Eva , Ellinghaus, David , Stanulla, Martin , Clavel, Jacqueline , Orsi, Laurent , Pasquini, Marcelo C. , Sucheston‐Campbell, Lara E. , Clay-Gilmour, Alyssa I, Ellinghaus, David , Weisdorf, Dan , Clavel, Jacqueline , Stram, Daniel O. , Hu, Qiang , Ambrosone, Christine B. , Spellman, Stephen R. , McCarthy, Philip L.
Blood Advances | October 10, 2019 | Volume: 1 | Issue: 20 | Pages: 1717-1728
10.1182/bloodadvances.2017006023
Key PointsIKZF1 associations with high-risk B-ALL may differ by age and sex. A novel variant on chromosome 14, rs189434316, is associated with over a 3.5-fold risk of normal cytogenetic B-ALL.
Polymorphic Variation in TPMT Is the Principal Determinant of TPMT Phenotype: A Meta‐Analysis of Three Genome‐Wide Association Studies
Tamm, R, Mägi, Reedik , Tremmel, Roman , Winter, Stefan , Mihailov, Evelin, Smid, A., Möricke, Anja , Klein, Kathrin , Stanulla, Martin , Houlston, Richard S. , Weinshilboum, Richard M. , Mlinarič‐Raščan, Irena , Milani, Lili , Schwab, Matthias , Schaeffeler, Elke , Tamm, Riin, Schrappe, Martin , Weinshilboum, Richard M. , Metspalu, Andres , Houlston, Richard S , Tremmel, Roman , Schwab, Matthias
Clinical Pharmacology & Therapeutics | October 22, 2016 | Volume: 101 | Issue: 5 | Pages: 684-695
Thiopurine‐related hematotoxicity in pediatric acute lymphoblastic leukemia (ALL) and inflammatory bowel diseases has been linked to genetically defined variability in thiopurine S‐methyltransferase (TPMT) activity. While gene testing of TPMT is being clinically implemented, it is unclear if additional genetic variation influences TPMT activity with consequences for thiopurine‐related toxicity. To examine this possibility, we performed a genome‐wide association study (GWAS) of red blood cell TPMT activity in 844 Estonian individuals and 245 pediatric ALL cases. Additionally, we correlated genome‐wide genotypes to human hepatic TPMT activity in 123 samples. Only genetic variants mapping to chromosome 6, including the TPMT gene region, were significantly associated with TPMT activity ( P < 5.0 × 10 ‐8 ) in each of the three GWAS and a joint meta‐analysis of 1,212 cases (top hit P = 1.2 × 10 ‐72 ). This finding is consistent with TPMT genotype being the primary determinant of TPMT activity, reinforcing the rationale for genetic testing of TPMT alleles in routine clinical practice to individualize mercaptopurine dosage.