White matter lesion progression: genome-wide search for genetic influences
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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White matter lesion progression : genome-wide search for genetic influences. / Hofer, Edith; Cavalieri, Margherita; Bis, Joshua C; DeCarli, Charles; Fornage, Myriam; Sigurdsson, Sigurdur; Srikanth, Velandai; Trompet, Stella; Verhaaren, Benjamin F J; Wolf, Christiane; Yang, Qiong; Adams, Hieab H H; Amouyel, Philippe; Beiser, Alexa; Buckley, Brendan M; Callisaya, Michele; Chauhan, Ganesh; de Craen, Anton J M; Dufouil, Carole; van Duijn, Cornelia M; Ford, Ian; Freudenberger, Paul; Gottesman, Rebecca F; Gudnason, Vilmundur; Heiss, Gerardo; Hofman, Albert; Lumley, Thomas; Martinez, Oliver; Mazoyer, Bernard; Moran, Chris; Niessen, Wiro J.; Phan, Thanh; Psaty, Bruce M; Satizabal, Claudia L; Sattar, Naveed; Schilling, Sabrina; Shibata, Dean K; Slagboom, P Eline; Smith, Albert; Stott, David J; Taylor, Kent D; Thomson, Russell; Töglhofer, Anna M; Tzourio, Christophe; van Buchem, Mark; Wang, Jing; Westendorp, Rudi G. J.; Windham, B Gwen; Vernooij, Meike W; Zijdenbos, Alex; Beare, Richard; Debette, Stéphanie; Ikram, M Arfan; Jukema, J Wouter; Launer, Lenore J; Longstreth, W T; Mosley, Thomas H; Seshadri, Sudha; Schmidt, Helena; Schmidt, Reinhold.
I: Stroke, Bind 46, 2015, s. 3048-3057.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - White matter lesion progression
T2 - genome-wide search for genetic influences
AU - Hofer, Edith
AU - Cavalieri, Margherita
AU - Bis, Joshua C
AU - DeCarli, Charles
AU - Fornage, Myriam
AU - Sigurdsson, Sigurdur
AU - Srikanth, Velandai
AU - Trompet, Stella
AU - Verhaaren, Benjamin F J
AU - Wolf, Christiane
AU - Yang, Qiong
AU - Adams, Hieab H H
AU - Amouyel, Philippe
AU - Beiser, Alexa
AU - Buckley, Brendan M
AU - Callisaya, Michele
AU - Chauhan, Ganesh
AU - de Craen, Anton J M
AU - Dufouil, Carole
AU - van Duijn, Cornelia M
AU - Ford, Ian
AU - Freudenberger, Paul
AU - Gottesman, Rebecca F
AU - Gudnason, Vilmundur
AU - Heiss, Gerardo
AU - Hofman, Albert
AU - Lumley, Thomas
AU - Martinez, Oliver
AU - Mazoyer, Bernard
AU - Moran, Chris
AU - Niessen, Wiro J.
AU - Phan, Thanh
AU - Psaty, Bruce M
AU - Satizabal, Claudia L
AU - Sattar, Naveed
AU - Schilling, Sabrina
AU - Shibata, Dean K
AU - Slagboom, P Eline
AU - Smith, Albert
AU - Stott, David J
AU - Taylor, Kent D
AU - Thomson, Russell
AU - Töglhofer, Anna M
AU - Tzourio, Christophe
AU - van Buchem, Mark
AU - Wang, Jing
AU - Westendorp, Rudi G. J.
AU - Windham, B Gwen
AU - Vernooij, Meike W
AU - Zijdenbos, Alex
AU - Beare, Richard
AU - Debette, Stéphanie
AU - Ikram, M Arfan
AU - Jukema, J Wouter
AU - Launer, Lenore J
AU - Longstreth, W T
AU - Mosley, Thomas H
AU - Seshadri, Sudha
AU - Schmidt, Helena
AU - Schmidt, Reinhold
N1 - © 2015 American Heart Association, Inc.
PY - 2015
Y1 - 2015
N2 - 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.
AB - 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.
U2 - 10.1161/STROKEAHA.115.009252
DO - 10.1161/STROKEAHA.115.009252
M3 - Journal article
C2 - 26451028
VL - 46
SP - 3048
EP - 3057
JO - Stroke
JF - Stroke
SN - 0039-2499
ER -
ID: 146206866