Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome

Neda Jahanshad; Derrek P. Hibar; April Ryles; Arthur W. Toga; Katie L. McMahon; Greig I. De Zubicaray; Narelle K. Hansell; Grant W. Montgomery; Nicholas G. Martin; Margaret J. Wright; Paul M. Thompson

doi:10.1109/ISBI.2012.6235605

Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome

Neda Jahanshad
, Derrek P. Hibar
, April Ryles
, Arthur W. Toga
, Katie L. McMahon
, Greig I. De Zubicaray
, Narelle K. Hansell
, Grant W. Montgomery
, Nicholas G. Martin
, Margaret J. Wright
, Paul M. Thompson

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

19 Scopus citations

Abstract

Human brain connectivity is disrupted in a wide range of disorders from Alzheimer's disease to autism but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high angular resolution diffusion imaging (105-gradient HARDI). Using whole brain HARDI tractography, we extracted a relatively sparse 70×70 matrix representing fiber density between all pairs of cortical regions automatically labeled in co-registered anatomical scans. Additive genetic factors accounted for 1-58% of the variance in connectivity between 90 (of 122) tested nodes. We discovered genome-wide significant associations between variants and connectivity. GWAS permutations at various levels of heritability, and split-sample replication, validated our genetic findings. The resulting genes may offer new leads for mechanisms influencing aberrant connectivity and neurodegeneration.

Original language	English
Title of host publication	2012 9th IEEE International Symposium on Biomedical Imaging
Subtitle of host publication	From Nano to Macro, ISBI 2012 - Proceedings
Publisher	IEEE Computer Society
Pages	542-545
Number of pages	4
ISBN (Print)	9781457718588
DOIs	https://doi.org/10.1109/ISBI.2012.6235605
State	Published - 2012
Externally published	Yes
Event	9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012 - Barcelona, Spain Duration: 2 May 2012 → 5 May 2012

Publication series

Name	Proceedings - International Symposium on Biomedical Imaging
ISSN (Print)	1945-7928
ISSN (Electronic)	1945-8452

Conference

Conference	9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012
Country/Territory	Spain
City	Barcelona
Period	2/05/12 → 5/05/12

Keywords

cortical surfaces
genetics
high angular resolution diffusion imaging (HARDI)
human connectome
twin modeling

Access to Document

10.1109/ISBI.2012.6235605

Cite this

Jahanshad, N., Hibar, D. P., Ryles, A., Toga, A. W., McMahon, K. L., De Zubicaray, G. I., Hansell, N. K., Montgomery, G. W., Martin, N. G., Wright, M. J., & Thompson, P. M. (2012). Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome. In 2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012 - Proceedings (pp. 542-545). Article 6235605 (Proceedings - International Symposium on Biomedical Imaging). IEEE Computer Society. https://doi.org/10.1109/ISBI.2012.6235605

@inproceedings{7a1c7c092c3f4c3394244402db951cd6,

title = "Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome",

abstract = "Human brain connectivity is disrupted in a wide range of disorders from Alzheimer's disease to autism but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high angular resolution diffusion imaging (105-gradient HARDI). Using whole brain HARDI tractography, we extracted a relatively sparse 70×70 matrix representing fiber density between all pairs of cortical regions automatically labeled in co-registered anatomical scans. Additive genetic factors accounted for 1-58\% of the variance in connectivity between 90 (of 122) tested nodes. We discovered genome-wide significant associations between variants and connectivity. GWAS permutations at various levels of heritability, and split-sample replication, validated our genetic findings. The resulting genes may offer new leads for mechanisms influencing aberrant connectivity and neurodegeneration.",

keywords = "cortical surfaces, genetics, high angular resolution diffusion imaging (HARDI), human connectome, twin modeling",

author = "Neda Jahanshad and Hibar, \{Derrek P.\} and April Ryles and Toga, \{Arthur W.\} and McMahon, \{Katie L.\} and \{De Zubicaray\}, \{Greig I.\} and Hansell, \{Narelle K.\} and Montgomery, \{Grant W.\} and Martin, \{Nicholas G.\} and Wright, \{Margaret J.\} and Thompson, \{Paul M.\}",

year = "2012",

doi = "10.1109/ISBI.2012.6235605",

language = "English",

isbn = "9781457718588",

series = "Proceedings - International Symposium on Biomedical Imaging",

publisher = "IEEE Computer Society",

pages = "542--545",

booktitle = "2012 9th IEEE International Symposium on Biomedical Imaging",

address = "United States",

note = "9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012 ; Conference date: 02-05-2012 Through 05-05-2012",

}

Jahanshad, N, Hibar, DP, Ryles, A, Toga, AW, McMahon, KL, De Zubicaray, GI, Hansell, NK, Montgomery, GW, Martin, NG, Wright, MJ & Thompson, PM 2012, Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome. in 2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012 - Proceedings., 6235605, Proceedings - International Symposium on Biomedical Imaging, IEEE Computer Society, pp. 542-545, 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012, Barcelona, Spain, 2/05/12. https://doi.org/10.1109/ISBI.2012.6235605

Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome. / Jahanshad, Neda; Hibar, Derrek P.; Ryles, April et al.
2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012 - Proceedings. IEEE Computer Society, 2012. p. 542-545 6235605 (Proceedings - International Symposium on Biomedical Imaging).

Research output: Chapter in Book/Report/Conference proceeding › Conference contribution › peer-review

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AU - Toga, Arthur W.

AU - McMahon, Katie L.

AU - De Zubicaray, Greig I.

AU - Hansell, Narelle K.

AU - Montgomery, Grant W.

AU - Martin, Nicholas G.

AU - Wright, Margaret J.

AU - Thompson, Paul M.

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N2 - Human brain connectivity is disrupted in a wide range of disorders from Alzheimer's disease to autism but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high angular resolution diffusion imaging (105-gradient HARDI). Using whole brain HARDI tractography, we extracted a relatively sparse 70×70 matrix representing fiber density between all pairs of cortical regions automatically labeled in co-registered anatomical scans. Additive genetic factors accounted for 1-58% of the variance in connectivity between 90 (of 122) tested nodes. We discovered genome-wide significant associations between variants and connectivity. GWAS permutations at various levels of heritability, and split-sample replication, validated our genetic findings. The resulting genes may offer new leads for mechanisms influencing aberrant connectivity and neurodegeneration.

AB - Human brain connectivity is disrupted in a wide range of disorders from Alzheimer's disease to autism but little is known about which specific genes affect it. Here we conducted a genome-wide association for connectivity matrices that capture information on the density of fiber connections between 70 brain regions. We scanned a large twin cohort (N=366) with 4-Tesla high angular resolution diffusion imaging (105-gradient HARDI). Using whole brain HARDI tractography, we extracted a relatively sparse 70×70 matrix representing fiber density between all pairs of cortical regions automatically labeled in co-registered anatomical scans. Additive genetic factors accounted for 1-58% of the variance in connectivity between 90 (of 122) tested nodes. We discovered genome-wide significant associations between variants and connectivity. GWAS permutations at various levels of heritability, and split-sample replication, validated our genetic findings. The resulting genes may offer new leads for mechanisms influencing aberrant connectivity and neurodegeneration.

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DO - 10.1109/ISBI.2012.6235605

M3 - Conference contribution

AN - SCOPUS:84864834756

SN - 9781457718588

T3 - Proceedings - International Symposium on Biomedical Imaging

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EP - 545

BT - 2012 9th IEEE International Symposium on Biomedical Imaging

PB - IEEE Computer Society

Y2 - 2 May 2012 through 5 May 2012

ER -

Jahanshad N, Hibar DP, Ryles A, Toga AW, McMahon KL, De Zubicaray GI et al. Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome. In 2012 9th IEEE International Symposium on Biomedical Imaging: From Nano to Macro, ISBI 2012 - Proceedings. IEEE Computer Society. 2012. p. 542-545. 6235605. (Proceedings - International Symposium on Biomedical Imaging). doi: 10.1109/ISBI.2012.6235605

Discovery of genes that affect human brain connectivity: A genome-wide analysis of the connectome

Abstract

Publication series

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Keywords

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