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Alvarez, I.

Publications and source records attributed to Alvarez, I..

2 recordsLinked to original sources
bioRxiv2019

Normative cerebral cortical thickness for human visual areas

1Studies of changes in cerebral neocortical thickness often rely on small control samples for comparison with specific populations with abnormal visual systems. We present a normative dataset for FreeSurfer-derived cortical thickness across 25 human visual areas derived from 960 participants in the Human Connectome Project. Cortical thickness varies systematically across visual areas, in broad agreement with canonical visual system hierarchies in the dorsal and ventral pathways. In addition, cortical thickness estimates show consistent within-subject variability and reliability. Importantly, cortical thickness estimates in visual areas are well described by a normal distribution, making them amenable to direct statistical comparison.\n\nHighlightsO_LINormative neocortical thickness values for human visual areas measured with FreeSurfer\nC_LIO_LIA gradient of increasing neocortical thickness with visual area hierarchy\nC_LIO_LIConsistent within- and between-subject variability in neocortical thickness across visual areas\nC_LI

neuroscience↗
bioRxiv2019

The genetic architecture of Parkinson disease in Spain: characterizing population-specific risk, differential haplotype structures, and providing etiologic insight

BackgroundThe Iberian Peninsula stands out as having variable levels of population admixture and isolation, making Spain an interesting setting for studying the genetic architecture of neurodegenerative diseases.\n\nObjectivesTo perform the largest Parkinson disease (PD) genome-wide association study (GWAS) restricted to a single country.\n\nMethodsWe performed a GWAS for both risk of PD and age-at-onset (AAO) in 7,849 Spanish individuals. Further analyses included population-specific risk haplotype assessments, polygenic risk scoring through machine learning, Mendelian randomization of expression and methylation data to gain insight into disease-associated loci, heritability estimates, genetic correlations and burden analyses.\n\nResultsWe identified a novel population-specific GWAS signal at PARK2 associated with AAO. We replicated four genome-wide independent signals associated with PD risk, including SNCA, LRRK2, KANSL1/MAPT and HLA-DQB1. A significant trend for smaller risk haplotypes at known loci was found compared to similar studies of non-Spanish origin. Seventeen PD-related genes showed functional consequence via two-sample Mendelian randomization in expression and methylation datasets. Long runs of homozygosity at 28 known genes/loci were found to be enriched in cases versus controls.\n\nConclusionsOur data demonstrate the utility of the Spanish risk haplotype substructure for future fine-mapping efforts, showing how leveraging unique and diverse population histories can benefit genetic studies of complex diseases. The present study points to PARK2 as a major hallmark of PD etiology in Spain.

neuroscience↗