SARGURUPREMRAJ, Muralidharan; SUZUKI, H.; JIAN, X.; SARNOWSKI, C.; EVANS, T. E.; BIS, J. C.; EIRIKSDOTTIR, G.; SAKAUE, S.; TERZIKHAN, N.; HABES, M.; ZHAO, W.; ARMSTRONG, N. J.; HOFER, E.; YANEK, L. R.; HAGENAARS, S. P.; KUMAR, R. B.; VAN DEN AKKER, E. B.; MCWHIRTER, R. E.; TROMPET, S.; MISHRA, Aniket; SABA, Yasaman; SATIZABAL, C. L.; BEAUDET, G.; PETIT, L.; TSUCHIDA, A.; ZAGO, L.; SCHILLING, Sabrina; SIGURDSSON, S.; GOTTESMAN, R. F.; LEWIS, C. E.; AGGARWAL, N. T.; LOPEZ, O. L.; SMITH, J. A.; VALDES HERNANDEZ, M. C.; VAN DER GROND, J.; WRIGHT, M. J.; KNOL, M. J.; DORR, M.; THOMSON, R. J.; BORDES, Constance; LE GRAND, Quentin; DUPERRON, Marie-Gabrielle; SMITH, A. V.; KNOPMAN, D. S.; SCHREINER, P. J.; EVANS, D. A.; ROTTER, J. I.; BEISER, A. S.; MANIEGA, S. M.; BEEKMAN, M.; TROLLOR, J.; STOTT, D. J.; VERNOOIJ, M. W.; WITTFELD, K.; NIESSEN, W. J.; SOUMARE, A.; BOERWINKLE, E.; SIDNEY, S.; TURNER, S. T.; DAVIES, G.; THALAMUTHU, A.; VOLKER, U.; VAN BUCHEM, M. A.; BRYAN, R. N.; DUPUIS, J.; BASTIN, M. E.; AMES, D.; TEUMER, A.; AMOUYEL, Philippe; KWOK, J. B.; BULOW, R.; DEARY, I. J.; SCHOFIELD, P. R.; BRODATY, H.; JIANG, J.; TABARA, Y.; SETOH, K.; MIYAMOTO, S.; YOSHIDA, K.; NAGATA, M.; KAMATANI, Y.; MATSUDA, F.; PSATY, B. M.; BENNETT, D. A.; DE JAGER, P. L.; MOSLEY, T. H.; SACHDEV, P. S.; SCHMIDT, R.; WARREN, H. R.; EVANGELOU, E.; TREGOUET, David-Alexandre; INTERNATIONAL NETWORK AGAINST THROMBOSIS, Consortium; INTERNATIONAL HEADACHE GENOMICS, Consortium; IKRAM, M. A.; WEN, W.; DECARLI, C.; SRIKANTH, V. K.; JUKEMA, J. W.; SLAGBOOM, E. P.; KARDIA, S. L. R.; OKADA, Y.; MAZOYER, Bernard; WARDLAW, J. M.; NYQUIST, P. A.; MATHER, K. A.; GRABE, H. J.; SCHMIDT, H.; VAN DUIJN, C. M.; GUDNASON, V.; LONGSTRETH, W. T., Jr.; LAUNER, L. J.; LATHROP, M.; SESHADRI, Sudha; TZOURIO, Christophe; ADAMS, H. H.; MATTHEWS, P. M.; FORNAGE, M.; DEBETTE, Stephanie

doi:10.1038/s41467-020-19111-2

Bordeaux population health [BPH]

SUZUKI, H.

JIAN, X.

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Article de revue

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Nature Communications. 2020-12-08, vol. 11, n° 1, p. 6285

Resumen en inglés

White matter hyperintensities (WMH) are the most common brain-imaging feature of cerebral small vessel disease (SVD), hypertension being the main known risk factor. Here, we identify 27 genome-wide loci for WMH-volume in a cohort of 50,970 older individuals, accounting for modification/confounding by hypertension. Aggregated WMH risk variants were associated with altered white matter integrity (p = 2.5x10-7) in brain images from 1,738 young healthy adults, providing insight into the lifetime impact of SVD genetic risk. Mendelian randomization suggested causal association of increasing WMH-volume with stroke, Alzheimer-type dementia, and of increasing blood pressure (BP) with larger WMH-volume, notably also in persons without clinical hypertension. Transcriptome-wide colocalization analyses showed association of WMH-volume with expression of 39 genes, of which four encode known drug targets. Finally, we provide insight into BP-independent biological pathways underlying SVD and suggest potential for genetic stratification of high-risk individuals and for genetically-informed prioritization of drug targets for prevention trials.< Leer menos

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https://oskar-bordeaux.fr/handle/20.500.12278/26449

DOI

http://dx.doi.org/10.1038/s41467-020-19111-2

Centros de investigación

Bordeaux Population Health Research Center (BPH) - UMR 1219

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Cerebral small vessel disease genomics and its implications across the lifespan

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Resumen en inglés

URI

DOI

Centros de investigación