Title | White Matter Lesion Progression: Genome-Wide Search for Genetic Influences. |
Publication Type | Journal Article |
Year of Publication | 2015 |
Authors | Hofer 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 Authors | Schmidt R |
Corporate Authors | Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium |
Journal | Stroke |
Volume | 46 |
Issue | 11 |
Pagination | 3048-57 |
Date Published | 2015 Nov |
ISSN | 1524-4628 |
Keywords | Adult, 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. |
DOI | 10.1161/STROKEAHA.115.009252 |
Alternate Journal | Stroke |
PubMed ID | 26451028 |
PubMed Central ID | PMC4749149 |
Grant List | R01 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 |