Citations 2
Genetic variants in CETP increase risk of intracerebral hemorrhage
Anderson, Christopher D. , Falcone, Guido J. , Phuah, Chia‐Ling , Radmanesh, Farid , Brouwers, H. Bart , Battey, Thomas W.K., Biffi, Alessandro , Liu, Dajiang J. , Viswanathan, Anand , Greenberg, Steven M. , Brown, Devin L. , Worrall, Bradford B. , Silliman, Scott, Tirschwell, David , Flaherty, Matthew L. , Kraft, Peter , Jagiełła, Jeremiasz , Schmidt, Helena , Hansen, Björn M. , Jiménez-Conde, Jordi , Giralt‐Steinhauer, Eva , Elosúa, Roberto , Cuadrado‐Godia, Elisa , Soriano‐Tárraga, Carolina , Nieuwenhuizen, Koen M. van , Klijn, Catharina J.M. , Rannikmäe, Kristiina , Samarasekera, Neshika , Salman, Rustam Al‐Shahi , Sudlow, Catherine L., Deary, Ian J. , Morotti, Andrea , Pezzini, Alessandro , Pera, Joanna , Urbanik, Andrzej, Pichler, Alexander , Montaner, Joan , Fernández‐Cadenas, Israel , Delgado, Pilar , Słowik, Agnieszka , Schmidt, Reinhold, Kidwell, Chelsea S., Kittner, Steven J. , Waddy, Salina P., Langefeld, Carl D. , Kathiresan, Sekar , Woo, Daniel , Sudlow, Cathie , Lee, Chaeyoung , Meschia, James F , van Nieuwenhuizen, Koen M , Peloso, Gina M. , Ayres, Alison M. , Goldstein, Joshua Norkin , Selim, Magdy H. , Meschia, James F. , Enzinger, Christian , Norrving, Bo , Roquer, Jaume , Lindgren, Arne G. , Abecasis, Gonçalo R. , Willer, Cristen J , Rosand, Jonathan M. , Kraft, Peter , Montaner, Joan , Pezzini, Alessandro , Al-Shahi Salman, Rustam
Annals of Neurology | September 22, 2016 | Volume: 80 | Issue: 5 | Pages: 730-740
ObjectiveIn observational epidemiologic studies, higher plasma high‐density lipoprotein cholesterol (HDL‐C) has been associated with increased risk of intracerebral hemorrhage (ICH). DNA sequence variants that decrease cholesteryl ester transfer protein (CETP) gene activity increase plasma HDL‐C; as such, medicines that inhibit CETP and raise HDL‐C are in clinical development. Here, we test the hypothesis that CETP DNA sequence variants associated with higher HDL‐C also increase risk for ICH.MethodsWe performed 2 candidate‐gene analyses of CETP. First, we tested individual CETP variants in a discovery cohort of 1,149 ICH cases and 1,238 controls from 3 studies, followed by replication in 1,625 cases and 1,845 controls from 5 studies. Second, we constructed a genetic risk score comprised of 7 independent variants at the CETP locus and tested this score for association with HDL‐C as well as ICH risk.ResultsTwelve variants within CETP demonstrated nominal association with ICH, with the strongest association at the rs173539 locus (odds ratio [OR] = 1.25, standard error [SE] = 0.06, p = 6.0 × 10−4) with no heterogeneity across studies (I2 = 0%). This association was replicated in patients of European ancestry (p = 0.03). A genetic score of CETP variants found to increase HDL‐C by ∼2.85mg/dl in the Global Lipids Genetics Consortium was strongly associated with ICH risk (OR = 1.86, SE = 0.13, p = 1.39 × 10−6).InterpretationGenetic variants in CETP associated with increased HDL‐C raise the risk of ICH. Given ongoing therapeutic development in CETP inhibition and other HDL‐raising strategies, further exploration of potential adverse cerebrovascular outcomes may be warranted. Ann Neurol 2016;80:730–740
Regional cortical thinning in multiple sclerosis and its relation with cognitive impairment: A multicenter study
Tillema, JM, Hulst, Hanneke E. , Rocca, Maria A. , Vrenken, Hugo , Steenwijk, MD, Damjanovic, Dusan , Tedeschi, Gioacchino , Gallo, Antonio , Ciccarelli, Olga , Montalbán, Xavier , Stefano, Nicola De , Stromillo, ML, Filippi, Massimo , Barkhof, Frederik , Group, on behalf of the MAGNIMS Study, Tillema, JM, Enzinger, Christian , Ropele, Stefan , Rovira, Àlex , Group, on behalf of the MAGNIMS Study, Filippi, Massimo , Barkhof, Frederik , Rocca, Maria A , Ciccarelli, Olga
Multiple Sclerosis Journal | October 2, 2015 | Volume: 22 | Issue: 7 | Pages: 901-909
Objectives: The objectives of this paper are to compare in a multicenter setting patterns of regional cortical thickness in patients with relapsing–remitting multiple sclerosis (RRMS) and cognitive impairment (CI) and those cognitively preserved (CP), and explore the relationship between cortical thinning and cognitive performance. Methods: T1-weighted isotropic brain scans were collected at 3T from seven European centers in 60 RRMS patients and 65 healthy controls (HCs). Patients underwent clinical and neuropsychological examinations. Cortical thickness (CTh) measures were calculated using FreeSurfer (failing in four) and both lobar and vertex-based general linear model (GLM) analyses were compared between study groups. Results: Twenty (36%) MS patients were classified as CI. Mean global CTh was smaller in RRMS patients compared to HCs (left 2.43 vs. 2.53 mm, right 2.44 vs. 2.54 mm, p < 0.001). Multivariate GLM regional analysis showed significantly more temporal thinning in CI compared to CP patients. Verbal memory scores correlated to regional cortical thinning in the insula whereas visual memory scores correlated to parietal thinning. Conclusions: This multicenter study showed mild global cortical thinning in RRMS. The extent of thinning is less pronounced than previously reported. Only subtle regional differences between CI and CP patients were observed, some of which related to specific cognitive domains.