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White Matter Lesion Progression: Genome-Wide Search for Genetic Influences.

TitleWhite Matter Lesion Progression: Genome-Wide Search for Genetic Influences.
Publication TypeJournal Article
Year of Publication2015
AuthorsHofer E, Cavalieri M, Bis JC, DeCarli C, Fornage M, Sigurdsson S, Srikanth V, Trompet S, Verhaaren BFJ, Wolf C, Yang Q, Adams HHH, Amouyel P, Beiser A, Buckley BM, Callisaya M, Chauhan G, de Craen AJM, Dufouil C, van Duijn CM, Ford I, Freudenberger P, Gottesman RF, Gudnason V, Heiss G, Hofman A, Lumley T, Martinez O, Mazoyer B, Moran C, Niessen WJ, Phan T, Psaty BM, Satizabal CL, Sattar N, Schilling S, Shibata DK, P Slagboom E, Smith A, Stott DJ, Taylor KD, Thomson R, Töglhofer AM, Tzourio C, van Buchem M, Wang J, Westendorp RGJ, B Windham G, Vernooij MW, Zijdenbos A, Beare R, Debette S, M Ikram A, J Jukema W, Launer LJ, Longstreth WT, Mosley TH, Seshadri S, Schmidt H
Secondary AuthorsSchmidt R
Corporate AuthorsCohorts for Heart and Aging Research in Genomic Epidemiology Consortium
JournalStroke
Volume46
Issue11
Pagination3048-57
Date Published2015 Nov
ISSN1524-4628
KeywordsAdult, Aged, Cohort Studies, Disease Progression, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Leukoencephalopathies, Male, Middle Aged, Prospective Studies, White Matter
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

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.

DOI10.1161/STROKEAHA.115.009252
Alternate JournalStroke
PubMed ID26451028
PubMed Central IDPMC4749149
Grant ListR01 HL120393 / HL / NHLBI NIH HHS / United States
R01 HL087652 / HL / NHLBI NIH HHS / United States
HHSN268201100005I / HL / NHLBI NIH HHS / United States
R01HL105756 / HL / NHLBI NIH HHS / United States
R01AG023629 / AG / NIA NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
U01HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
N02-HL-6-4278 / HL / NHLBI NIH HHS / United States
N01-HC-25195 / HC / NHLBI NIH HHS / United States
R01 HL103612 / HL / NHLBI NIH HHS / United States
HHSN268201100009I / HL / NHLBI NIH HHS / United States
UL1TR000124 / TR / NCATS NIH HHS / United States
R01 NS017950 / NS / NINDS NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
R01S AG08122 / AG / NIA NIH HHS / United States
R01 AG016495 / AG / NIA NIH HHS / United States
R01HL59367 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HHSN268201100005G / HL / NHLBI NIH HHS / United States
U01 HL096917 / HL / NHLBI NIH HHS / United States
HHSN268201100008I / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
R01 NS087541 / NS / NINDS NIH HHS / United States
R01 U0149505 / / PHS HHS / United States
R01 NS17950 / NS / NINDS NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100011I / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
HHSN268200625226C / / PHS HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
HL093029 / HL / NHLBI NIH HHS / United States
R01 HL093029 / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
N01HC85086 / HL / NHLBI NIH HHS / United States
R01 HL105756 / HL / NHLBI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
/ ImNIH / Intramural NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
HHSN268200800007C / HL / NHLBI NIH HHS / United States
R01HL087652 / HL / NHLBI NIH HHS / United States
N01HC85082 / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
R01 HL070825 / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
N01HC85083 / HL / NHLBI NIH HHS / United States
HHSN268201100005C / HL / NHLBI NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
HHSN268201100007I / HL / NHLBI NIH HHS / United States
N01HC15103 / HC / NHLBI NIH HHS / United States
HHSN268201200036C / HL / NHLBI NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
R01HL103612 / HL / NHLBI NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
R01 AG023629 / AG / NIA NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
N01HC85080 / HL / NHLBI NIH HHS / United States
R01HL120393 / HL / NHLBI NIH HHS / United States
R01 AG16495 / AG / NIA NIH HHS / United States
U01 AG049505 / AG / NIA NIH HHS / United States
N01HC85081 / HL / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States