Measurement and genetics of human subcortical and hippocampal asymmetries in large datasets.
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.
Language and Genetics Department, Max Planck Institute for Psycholinguistics, Nijmegen, The Netherlands; International Max Planck Research School for Language Sciences, Max Planck Insitute for Psycholinguistics, Nijmegen, The Netherlands.
Tulio
T
Guadalupe
Marcel P
MP
Zwiers
Alexander
A
Teumer
Katharina
K
Wittfeld
Alejandro Arias
AA
Vasquez
Martine
M
Hoogman
Peter
P
Hagoort
Guillen
G
Fernandez
Jan
J
Buitelaar
Katrin
K
Hegenscheid
Henry
H
Völzke
Barbara
B
Franke
Simon E
SE
Fisher
Hans J
HJ
Grabe
Clyde
C
Francks
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology*; D001931:Brain Mapping; D018672:Community Health Planning; D066264:Datasets as Topic; D005260:Female; D005500:Follow-Up Studies; D007839:Functional Laterality / Q000235:genetics*; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D013223:Statistics as Topic; D055815:Young Adult
asymmetry; brain; caudate nucleus; genetics; genome-wide association scan; lateralization; magnetic resonance imaging; subcortical; volumetry