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White Matter Lesion Progression: Genome-Wide Search for Genetic Influences.
Wednesday,2015-10-14 14:19 America/Los_Angeles — zdrager
| 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, Ikram, AM, J Jukema, W, Launer, LJ, Longstreth, WT, Mosley, TH, Seshadri, S, Schmidt, H, Schmidt, R |
| Corporate/Institutional 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 | <p><b>BACKGROUND AND PURPOSE: </b>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.</p><p><b>METHODS: </b>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.</p><p><b>RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>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.</p> |
| DOI | 10.1161/STROKEAHA.115.009252 |
| Alternate Journal | Stroke |
| PubMed ID | 26451028 |
| PubMed Central ID | PMC4749149 |
| Grant List | HHSN268200625226C / / PHS HHS / United States HHSN268200800007C / / PHS HHS / United States HHSN268201100005C / / PHS HHS / United States HHSN268201100006C / / PHS HHS / United States HHSN268201100007C / / PHS HHS / United States HHSN268201100008C / / PHS HHS / United States HHSN268201100009C / / PHS HHS / United States HHSN268201100010C / / PHS HHS / United States HHSN268201100011C / / PHS HHS / United States HHSN268201100012C / / PHS HHS / United States HHSN268201200036C / / PHS HHS / United States HL093029 / HL / NHLBI NIH HHS / United States N01-AG-12100 / AG / NIA NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01HC15103 / HC / NHLBI NIH HHS / United States N01HC55222 / HC / NHLBI NIH HHS / United States N01HC85079 / HC / NHLBI NIH HHS / United States N01HC85080 / HC / NHLBI NIH HHS / United States N01HC85081 / HC / NHLBI NIH HHS / United States N01HC85082 / HC / NHLBI NIH HHS / United States N01HC85083 / HC / NHLBI NIH HHS / United States N01HC85086 / HC / NHLBI NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States R01 AG008122 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 AG033193 / AG / NIA NIH HHS / United States R01 AG16495 / AG / NIA NIH HHS / United States R01 HL093029 / HL / NHLBI NIH HHS / United States R01 NS087541 / NS / NINDS NIH HHS / United States R01 NS17950 / NS / NINDS NIH HHS / United States R01 U0149505 / / PHS HHS / United States R01AG023629 / AG / NIA NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States R01HL087652 / HL / NHLBI NIH HHS / United States R01HL103612 / HL / NHLBI NIH HHS / United States R01HL105756 / HL / NHLBI NIH HHS / United States R01HL120393 / HL / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States R01S AG08122 / AG / NIA NIH HHS / United States U01 HL096917 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States U01HL080295 / HL / NHLBI NIH HHS / United States UL1 TR000124 / TR / NCATS NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States UL1TR000124 / TR / NCATS NIH HHS / United States / / Intramural NIH HHS / United States |