Browsing by Author "Ripke, Stephan"
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- ItemInternational meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci(Nature Research (part of Springer Nature), 2019) Nievergelt, Caroline M.; Maihofer, Adam X.; Klengel, Torsten; Atkinson, Elizabeth G.; Chen, Chia-Yen; Choi, Karmel W.; Coleman, Jonathan R. I.; Dalvie, Shareefa; Duncan, Laramie E.; Gelernter, Joel; Levey, Daniel F.; Logue, Mark W.; Polimanti, Renato; Provost, Allison C.; Ratanatharathorn, Andrew; Stein, Murray B.; Torres, Katy; Aiello, Allison E.; Almli, Lynn M.; Amstadter, Ananda B.; Andersen, Soren B.; Andreassen, Ole A.; Arbisi, Paul A.; Ashley-Koch, Allison E.; Austin, S. Bryn; Avdibegovic, Esmina; Babic, Dragan; Bækvad-Hansen, Marie; Baker, Dewleen G.; Beckham, Jean C.; Bierut, Laura J.; Bisson, Jonathan I.; Boks, Marco P.; Bolger, Elizabeth A.; Borglum, Anders D.; Bradley, Bekh; Brashear, Megan; Breen, Gerome; Bryant, Richard A.; Bustamante, Angela C.; Bybjerg-Grauholm, Jonas; Calabrese, Joseph R.; Caldas-de-Almeida, Jose M.; Dale, Anders M.; Daly, Mark J.; Daskalakis, Nikolaos P.; Deckert, Jurgen; Delahanty, Douglas L.; Dennis, Michelle F.; Disner, Seth G.; Domschke, Katharina; Dzubur-Kulenovic, Alma; Erbes, Christopher R.; Evans, Alexandra; Farrer, Lindsay A.; Feeny, Norah C.; Flory, Janine D.; Forbes, David; Franz, Carol E.; Galea, Sandro; Garrett, Melanie E.; Gelaye, Bizu; Geuze, Elbert; Gillespie, Charles; Uka, Aferdita Goci; Goci, Aferdita; Guffanti, Guia; Hammamieh, Rasha; Harnal, Supriya; Hauser, Michael A.; Heath, Andrew C.; Hemmings, Sian M. J.; Hougaard, David Michael; Jakovljevic, Miro; Jett, Marti; Johnson, Eric Otto; Jones, Ian; Jovanovic, Tanja; Qin, Xue-Jun; Junglen, Angela G.; Karstoft, Karen-Inge; Kaufman, Milissa L.; Kessler, Ronald C.; Khan, Alaptagin; Kimbre, Nathan A.; King, Anthony P.; Koen, Nastassja; Kranzler, Henry R.; Kremen, William S.; Lawford, Bruce R.; Lebois, Lauren A. M.; Lewis, Catrin E.; Linnstaedt, Sarah D.; Lori, Adriana; Lugonja, Bozo; Luykx, Jurjen J.; Lyons, Michael J.; Maples-Keller, Jessica; Marmar, Charles; Martin, Alicia R.; Maurer, Douglas; Mavissakalian, Matig R.; McFarlane, Alexander; McGlinchey, Regina E.; McLaughlin, Katie A.; McLean, Samuel A.; McLeay, Sarah; Mehta, Divya; Milberg, William P.; Miller, Mark W.; Morey, Rajendra A.; Morris, Charles Phillip; Mors, Ole; Mortensen, Preben B.; Neale, Benjamin M.; Nelson, Elliot C.; Nordentoft, Merete; Norman, Sonya B.; O'Donnell, Meaghan; Orcutt, Holly K.; Panizzon, Matthew S.; Peters, Edward S.; Peterson, Alan L.; Peverill, Matthew; Pietrzak, Robert H.; Polusny, Melissa A.; Rice, John P.; Ripke, Stephan; Risbrough, Victoria B.; Roberts, Andrea L.; Rothbaum, Alex O.; Rothbaum, Barbara O.; Roy-Byrne, Peter; Ruggiero, Ken; Rung, Ariane; Rutten, Bart P. F.; Saccone, Nancy L.; Sanchez, Sixto E.; Schijven, Dick; Seedat, Soraya, 1966-; Seligowski, Antonia V.; Seng, Julia S.; Sheerin, Christina M.; Smith, Alicia K.; Smoller, Jordan W.; Sponheim, Scott R.; Stein, Dan J.; Stevens, Jennifer S.; Sumner, Jennifer A.; Teicher, Martin H.; Thompson, Wesley K.; Trapido, Edward; Uddin, Monica; Ursano, Robert J.; Van Den Heuvel, Leigh Luella; Van Hooff, Miranda; Vermetten, Eric; Vinkers, Christiaan H.; Voisey, Joanne; Wang, Yunpeng; Wang, Zhewu; Werge, Thomas; Williams, Michelle A.; Williamson, Douglas E.; Winternitz, Sherry; Wolf, Christiane; Wolf, Erika J.; Wolff, Jonathan D.; Yehuda, Rachel; Young, Ross McD; Young, Keith A.; Zhao, Hongyu; Zoellner, Lori A.; Liberzon, Israel; Ressler, Kerry J.; Haas, Magali; Koenen, Karestan C.The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5–20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson’s disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.
- ItemShared genetic risk factors of intracranial, abdominal, and thoracic aneurysms(American Heart Association, 2016-07-14) Van 't Hof, Femke N. G.; Ruigrok, Ynte M.; Lee, Cue Hyunkyu; Ripke, Stephan; Anderson, Graig; De Andrade, Mariza; Tromp, GerardBackground: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co‐occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. Methods and Results: We performed a mega‐analysis of 1000 Genomes Project‐imputed genome‐wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA‐, AAA‐, and TAA‐associated SNPs and tested these scores for association to case‐control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium–score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single‐nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10−5) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10−3). Conclusions: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication.