White matter lesion progression: genome-wide search for genetic influences

Edith Hofer, Margherita Cavalieri, Joshua C Bis, Charles S DeCarli, Myriam Fornage, Sigurdur Sigurdsson, Velandai Srikanth, Stella Trompet, Benjamin F J Verhaaren, Christiane Wolf, Qiong Yang, Hieab H H Adams, Philippe Amouyel, Alexa Beiser, Brendan M Buckley, Michele Callisaya, Ganesh Chauhan, Anton J M de Craen, Carole Dufouil, Cornelia M van DuijnIan Ford, Paul Freudenberger, Rebecca F Gottesman, Vilmundur G Gudnason, Gerardo Heiss, Albert Hofman, Thomas S Lumley, Oliver O Martinez, Bernard Mazoyer, Christopher Moran, Wiro J Niessen, Thanh G Phan, Bruce M Psaty, Claudia Liliana Satizabal, Naveed A Sattar, Sabrina Schilling, Dean K Shibata, Pieternella Eline Slagboom, Albert Vernon Smith, David J Stott, Kent D Taylor, Russell Thomson, Anna Maria Toglhofer, Christophe Tzourio, Mark A van Buchem, Jing Wang, Rudi G J Westendorp, Beverly Gwen Windham, Meike W Vernooij, Alex P Zijdenbos, Richard Beare, Stephanie Debette, Mohammed Arfan Ikram, J Wouter Jukema, Lenore J Launer, William T Longstreth Jr, Thomas H Mosley, Sudha Seshadri, Helena Schmidt, Reinhold Schmidt

Research output: Contribution to journalArticleResearchpeer-review

16 Citations (Scopus)


BACKGROUND AND PURPOSE: White matter lesion (WML) progression on magnetic resonance imaging is related to cognitive decline and stroke, but its determinants besides baseline WML burden are largely unknown. Here, we estimated heritability of WML progression, and sought common genetic variants associated with WML progression in elderly participants from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. METHODS: Heritability of WML progression was calculated in the Framingham Heart Study. The genome-wide association study included 7773 elderly participants from 10 cohorts. To assess the relative contribution of genetic factors to progression of WML, we compared in 7 cohorts risk models including demographics, vascular risk factors plus single-nucleotide polymorphisms that have been shown to be associated cross-sectionally with WML in the current and previous association studies. RESULTS: A total of 1085 subjects showed WML progression. The heritability estimate for WML progression was low at 6.5 , and no single-nucleotide polymorphisms achieved genome-wide significance (P
Original languageEnglish
Pages (from-to)3048 - 3057
Number of pages10
Issue number11
Publication statusPublished - 2015

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