White Matter Lesion Progression
Author:
Hofer Edith1, Cavalieri Margherita1, Bis Joshua C.1, DeCarli Charles1, Fornage Myriam1, Sigurdsson Sigurdur1, Srikanth Velandai1, Trompet Stella1, Verhaaren Benjamin F.J.1, Wolf Christiane1, Yang Qiong1, Adams Hieab H.H.1, Amouyel Philippe1, Beiser Alexa1, Buckley Brendan M.1, Callisaya Michele1, Chauhan Ganesh1, de Craen Anton J.M.1, Dufouil Carole1, van Duijn Cornelia M.1, Ford Ian1, Freudenberger Paul1, Gottesman Rebecca F.1, Gudnason Vilmundur1, Heiss Gerardo1, Hofman Albert1, Lumley Thomas1, Martinez Oliver1, Mazoyer Bernard1, Moran Chris1, Niessen Wiro J.1, Phan Thanh1, Psaty Bruce M.1, Satizabal Claudia L.1, Sattar Naveed1, Schilling Sabrina1, Shibata Dean K.1, Slagboom P. Eline1, Smith Albert1, Stott David J.1, Taylor Kent D.1, Thomson Russell1, Töglhofer Anna M.1, Tzourio Christophe1, van Buchem Mark1, Wang Jing1, Westendorp Rudi G.J.1, Gwen Windham B.1, Vernooij Meike W.1, Zijdenbos Alex1, Beare Richard1, Debette Stéphanie1, Ikram M. Arfan1, Jukema J. Wouter1, Launer Lenore J.1, Longstreth W. T.1, Mosley Thomas H.1, Seshadri Sudha1, Schmidt Helena1, Schmidt Reinhold1
Affiliation:
1. From the Department of Neurology (E.H., M.C., H.S., R.S.) and Institute for Medical Informatics, Statistics and Documentation (E.H.), Medical University of Graz, Graz, Austria; Cardiovascular Health Research Unit, Departments of Medicine (J.C.B., B.M.P.), Radiology (D.K.S.), and Neurology and Epidemiology (W.T.L.), University of Washington, Seattle; Department of Neurology and Center for Neuroscience, University of California at Davis, Sacramento (C.D.C., O.M.); Brown Foundation Institute of...
Abstract
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
<5×10
−8
). Four loci were suggestive (
P
<1×10
−5
) of an association with WML progression: 10q24.32 (rs10883817,
P
=1.46×10
−6
); 12q13.13 (rs4761974,
P
=8.71×10
−7
); 20p12.1 (rs6135309,
P
=3.69×10
−6
); and 4p15.31 (rs7664442,
P
=2.26×10
−6
). Variants that have been previously related to WML explained only 0.8% to 11.7% more of the variance in WML progression than age, vascular risk factors, and baseline WML burden.
Conclusions—
Common genetic factors contribute little to the progression of age-related WML in middle-aged and older adults. Future research on determinants of WML progression should focus more on environmental, lifestyle, or host-related biological factors.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Advanced and Specialised Nursing,Cardiology and Cardiovascular Medicine,Clinical Neurology
Cited by
21 articles.
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