Fennema‐Notestine, Christine
https://orcid.org/0000-0002-6527-6361
Mayo Clinic
University of California San Diego
Citations 2
Common Genetic Variation Indicates Separate Causes for Periventricular and Deep White Matter Hyperintensities
Armstrong, Nicola J. , Mather, Karen A. , Sargurupremraj, Muralidharan , Knol, Maria J. , Malik, Rainer, Satizábal, Claudia L. , Yanek, Lisa R., Wen, Wei , Guðnason, Vilmundur , Dueker, Nicole , Elliott, Lloyd T. , Hofer, Edith, Bis, Joshua C. , Jahanshad, Neda , Li, Shuo , Logue, Mark, Scholz, Markus , Smith, Albert V. , Trompet, Stella , Alfaro‐Almagro, Fidel , Ames, David, Amin, Najaf , Beiser, Alexa S., Brodaty, Henry , Fennema‐Notestine, Christine , Gampawar, Piyush , Gottesman, Rebecca, Griffanti, Ludovica , Kral, Brian G. , Lampe, Leonie, Liewald, David C. , Maillard, Pauline , Marchini, Jonathan, Bastin, Mark E., Pirpamer, Lukas , Roshchupkin, Gennady V. , Stott, David J., Thalamuthu, Anbupalam , Tzourio, Christophe , Grond, Jeroen van der , Vernooij, Meike W. , Witte, A. Veronica , Wright, Margaret J. , Yang, Qiong, Siggurdsson, Siggi, Psaty, Bruce M., Villringer, Arno , Schmidt, Helena, Duijn, Cornelia M. van , Jukema, J. Wouter , Dichgans, Martin , Sacco, Ralph L., Kremen, William S., Becker, Lewis C. , Thompson, Paul M., Mosley, Thomas H. , Wardlaw, Joanna M. , Ikram, M. Arfan , Adams, Hieab H.H. , Seshadri, Sudha , Sachdev, Perminder S. , Smith, Stephen M. , Launer, L. J., Longstreth, W.T. , DeCarli, Charles , Schmidt, Reinhold, Fornage, Myriam , Debette, Stéphanie , DeCarli, Charles , Dichgans, Martin , Wardlaw, Joanna Marguerite , Thalamuthu, Anbupalam , Wen, Wei , Adams, Hieab H H , Satizabal, Claudia L , Seshadri, Sudha , Brodaty, Henry , Sachdev, Perminder S , Wright, Margaret J , Tzourio, Christophe , van Duijn, Cornelia M , Debette, Stephanie , Smith, Albert V , Maillard, Pauline , Hofer, Edith , Luciano, Michelle , Vojinović, Dina , Xia, Rui , Amouyel, Philippe , Deary, Ian J. , Jack, Clifford R. , Jenkinson, Mark , Jiang, Jiyang , Kwok, John B. , Marchini, Jonathan , Mazoyer, Bernard , Romero, José R. , Schofield, Peter R. , Schroeter, Matthias L , Trollor, Julian N , Morris, Zoë , Psaty, Bruce M. , Håberg, Asta K , Wright, Clinton B. , Thompson, Paul M. , Nyquist, Paul
Stroke | June 10, 2020 | Volume: 51 | Issue: 7 | Pages: 2111-2121
Background and Purpose: Periventricular white matter hyperintensities (WMH; PVWMH) and deep WMH (DWMH) are regional classifications of WMH and reflect proposed differences in cause. In the first study, to date, we undertook genome-wide association analyses of DWMH and PVWMH to show that these phenotypes have different genetic underpinnings. Methods: Participants were aged 45 years and older, free of stroke and dementia. We conducted genome-wide association analyses of PVWMH and DWMH in 26,654 participants from CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology), ENIGMA (Enhancing Neuro-Imaging Genetics Through Meta-Analysis), and the UKB (UK Biobank). Regional correlations were investigated using the genome-wide association analyses -pairwise method. Cross-trait genetic correlations between PVWMH, DWMH, stroke, and dementia were estimated using LDSC. Results: In the discovery and replication analysis, for PVWMH only, we found associations on chromosomes 2 ( NBEAL ), 10q23.1 ( TSPAN14/FAM231A ), and 10q24.33 ( SH3PXD2A). In the much larger combined meta-analysis of all cohorts, we identified ten significant regions for PVWMH: chromosomes 2 (3 regions), 6, 7, 10 (2 regions), 13, 16, and 17q23.1. New loci of interest include 7q36.1 ( NOS3 ) and 16q24.2. In both the discovery/replication and combined analysis, we found genome-wide significant associations for the 17q25.1 locus for both DWMH and PVWMH. Using gene-based association analysis, 19 genes across all regions were identified for PVWMH only, including the new genes: CALCRL (2q32.1), KLHL24 (3q27.1), VCAN (5q27.1), and POLR2F (22q13.1). Thirteen genes in the 17q25.1 locus were significant for both phenotypes. More extensive genetic correlations were observed for PVWMH with small vessel ischemic stroke. There were no associations with dementia for either phenotype. Conclusions: Our study confirms these phenotypes have distinct and also shared genetic architectures. Genetic analyses indicated PVWMH was more associated with ischemic stroke whilst DWMH loci were implicated in vascular, astrocyte, and neuronal function. Our study confirms these phenotypes are distinct neuroimaging classifications and identifies new candidate genes associated with PVWMH only.
Magnetic resonance imaging in Alzheimer's Disease Neuroimaging Initiative 2
Jack, Clifford R. , Barnes, Josephine , Bernstein, Matt A. , Borowski, Bret, Brewer, James, Clegg, Shona , Dale, Anders M. , Carmichael, Owen , Ching, Christopher R. K. , DeCarli, Charles , Desikan, Rahul S. , Fennema‐Notestine, Christine , Fjell, Anders M. , Fox, Nick C. , Gunter, Jeff, Holland, Dominic , Hua, Xue , Kantarci, Kejal , Krueger, Gunnar, Leung, Kelvin K., Mackin, Scott, Maillard, Pauline , Malone, Ian B. , Mattsson, Niklas , McEvoy, Linda K. , Modat, Marc , Mueller, Susanne G. , Nosheny, Rachel L. , Ourselin, Sébastien , Schuff, Norbert, Senjem, Matthew L. , Simonson, Alix, Thompson, Paul M. , Rettmann, Dan , Vemuri, Prashanthi , Walhovd, Kristine B. , Zhao, Yansong , Zuk, Samantha M., Weiner, Michael W. , DeCarli, Charles , Borowski, Bret J, Zuk, Samantha, Fletcher, Evan M. , Gutman, Boris A , Insel, Philip S. , Killiany, Ronald , Bernstein, Matt A , Jack, Clifford R , Vemuri, Prashanthi , Dale, Anders M , Thompson, Paul M , Senjem, Matthew L , Ching, Christopher R K , Kantarci, Kejal , Fox, Nick C , Maillard, Pauline
Alzheimer's & Dementia | July 17, 2015 | Volume: 11 | Issue: 7 | Pages: 740-756
AbstractIntroductionAlzheimer's Disease Neuroimaging Initiative (ADNI) is now in its 10th year. The primary objective of the magnetic resonance imaging (MRI) core of ADNI has been to improve methods for clinical trials in Alzheimer's disease (AD) and related disorders.MethodsWe review the contributions of the MRI core from present and past cycles of ADNI (ADNI‐1, ‐Grand Opportunity and ‐2). We also review plans for the future‐ADNI‐3.ResultsContributions of the MRI core include creating standardized acquisition protocols and quality control methods; examining the effect of technical features of image acquisition and analysis on outcome metrics; deriving sample size estimates for future trials based on those outcomes; and piloting the potential utility of MR perfusion, diffusion, and functional connectivity measures in multicenter clinical trials.DiscussionOver the past decade the MRI core of ADNI has fulfilled its mandate of improving methods for clinical trials in AD and will continue to do so in the future.