Association of variants in HTRA1 and NOTCH3 with MRI-defined extremes of cerebral small vessel disease in older subjects

• Published in: Brain (London, England : 1878) Vol. 142; no. 4; pp. 1009 - 1023
• Main Authors: Mishra, Aniket, Chauhan, Ganesh, Violleau, Marie-Helene, Vojinovic, Dina, Jian, Xueqiu, Bis, Joshua C, Li, Shuo, Saba, Yasaman, Grenier-Boley, Benjamin, Yang, Qiong, Bartz, Traci M, Hofer, Edith, Soumaré, Aïcha, Peng, Fen, Duperron, Marie-Gabrielle, Foglio, Mario, Mosley, Thomas H, Schmidt, Reinhold, Psaty, Bruce M, Launer, Lenore J, Boerwinkle, Eric, Zhu, Yicheng, Mazoyer, Bernard, Lathrop, Mark, Bellenguez, Celine, Van Duijn, Cornelia M, Ikram, M Arfan, Schmidt, Helena, Longstreth, W T, Fornage, Myriam, Seshadri, Sudha, Joutel, Anne, Tzourio, Christophe, Debette, Stephanie
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.04.2019
• Subjects: Aged; Aged, 80 and over; Brain Ischemia - genetics; Cerebral Small Vessel Diseases - diagnostic imaging; Cerebral Small Vessel Diseases - genetics; Cerebral Small Vessel Diseases - metabolism; Cohort Studies; Exome Sequencing - methods; Female; Genetics; Geriatry and gerontology; Heterozygote; High-Temperature Requirement A Serine Peptidase 1 - genetics; High-Temperature Requirement A Serine Peptidase 1 - metabolism; Human genetics; Human health and pathology; Humans; Life Sciences; Magnetic Resonance Imaging; Male; Middle Aged; Mutation; Neurobiology; Neurons and Cognition; Original; Polymorphism, Single Nucleotide; Populations and Evolution; Receptor, Notch3 - genetics; Receptor, Notch3 - metabolism; Receptor, Notch3 - physiology; Stroke - genetics; White Matter - diagnostic imaging; White Matter - metabolism; exome sequencing study; cerebral small vessel disease; lacunes of presumed vascular origin; extreme phenotype; white matter hyperintensity

Mishra et al. present a composite extreme-phenotype strategy for gene mapping of cerebral small vessel disease in population cohorts of older persons. They identify associations with variants in HTRA1 and NOTCH3, and describe two participants heterozygous for known pathogenic variants for familial s...