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Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets.

Abstract：

:Functional and anatomical asymmetries are prevalent features of the human brain, linked to gender, handedness, and cognition. However, little is known about the neurodevelopmental processes involved. In zebrafish, asymmetries arise in the diencephalon before extending within the central nervous system. We aimed to identify genes involved in the development of subtle, left-right volumetric asymmetries of human subcortical structures using large datasets. We first tested the feasibility of measuring left-right volume differences in such large-scale samples, as assessed by two automated methods of subcortical segmentation (FSL|FIRST and FreeSurfer), using data from 235 subjects who had undergone MRI twice. We tested the agreement between the first and second scan, and the agreement between the segmentation methods, for measures of bilateral volumes of six subcortical structures and the hippocampus, and their volumetric asymmetries. We also tested whether there were biases introduced by left-right differences in the regional atlases used by the methods, by analyzing left-right flipped images. While many bilateral volumes were measured well (scan-rescan r = 0.6-0.8), most asymmetries, with the exception of the caudate nucleus, showed lower repeatabilites. We meta-analyzed genome-wide association scan results for caudate nucleus asymmetry in a combined sample of 3,028 adult subjects but did not detect associations at genome-wide significance (P < 5 × 10(-8) ). There was no enrichment of genetic association in genes involved in left-right patterning of the viscera. Our results provide important information for researchers who are currently aiming to carry out large-scale genome-wide studies of subcortical and hippocampal volumes, and their asymmetries.

journal_name

Hum Brain Mapp

journal_title

Human brain mapping

authors

Guadalupe T,Zwiers MP,Teumer A,Wittfeld K,Vasquez AA,Hoogman M,Hagoort P,Fernandez G,Buitelaar J,Hegenscheid K,Völzke H,Franke B,Fisher SE,Grabe HJ,Francks C

doi

10.1002/hbm.22401

subject

Has Abstract

pub_date

2014-07-01 00:00:00

pages

3277-89

issue

eissn

1065-9471

issn

1097-0193

journal_volume

pub_type

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Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets.