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Heritability of regional brain volumes in large-scale neuroimaging and genetic studies

By Bingxin Zhao, Joseph G. Ibrahim, Yun Li, Tengfei Li, Yue Wang, Yue Shan, Hongtu Zhu, Fan Zhou, Jingwen Zhang, Chao Huang, Huiling Liao, Liuqing Yang, Paul M. Thompson, Hongtu Zhu, Pediatric Imaging, Neurocognition and Genetics (PING), Connor McCabe, Linda Chang, Natacha Akshoomoff, Erik Newman, Thomas Ernst, Peter Van Zijl, Joshua Kuperman, Sarah Murray, Cinnamon Bloss, Mark Appelbaum, Anthony Gamst, Wesley Thompson, Hauke Bartsch, Alzheimer’s Disease Neuroimaging Initiative (ADNI), Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R. Jack, William Jagust, John Q. Trojanowki, Arthur W Toga, Laurel Beckett, Robert C. Green, Andrew J Saykin, John Morris, Leslie M. Shaw, Zaven Khachaturian, Greg Sorensen, Maria Carrillo, Lew Kuller, Marc Raichle, Steven Paul, Peter Davies, Howard Fillit, Franz Hefti, Davie Holtzman, M. Marcel Mesulman, William Potter, Peter J. Snyder, Adam Schwartz, Tom Montine, Ronald G. Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Gus Jiminez, Danielle Harvey, Matthew Bernstein, Nick Fox, Paul Thompson, Norbert Schuff, Charles DeCarli, Bret Borowski, Jeff Gunter, Matt Senjem, Prashanthi Vemuri, David Jones, Kejal Kantarci, Chad Ward, Robert A. Koeppe, Norm Foster, Eric M. Reiman, Kewei Chen, Chet Mathis, Susan Landau, Nigel J. Cairns, Erin Householder, Lisa Taylor-Reinwald, Virginia M.Y. Lee, Magdalena Korecka, Michal Figurski, Karen Crawford, Scott Neu, Tatiana M. Foroud, Steven Potkin, Li Shen, Kelley Faber, Sungeun Kim, Kwangsik Nho, Leon Thal, Richard Frank, Neil Buckholtz, Marilyn Albert, John Hsiao

Posted 25 Oct 2017
bioRxiv DOI: 10.1101/208496 (published DOI: 10.1093/cercor/bhy157)

Brain genetics is an active research area. The degree to which genetic variants impact variations in brain structure and function remains largely unknown. We examined the heritability of regional brain volumes (p ~ 100) captured by single-nucleotide polymorphisms (SNPs) in UK Biobank (n ~ 9000). We found that regional brain volumes are highly heritable in this study population. We observed omni-genic impact across the genome as well as enrichment of SNPs in active chromatin regions. Principal components derived from regional volume data are also highly heritable, but the amount of variance in brain volume explained by the component did not seem to be related to its heritability. Heritability estimates vary substantially across large-scale functional networks and brain regions. The variation in heritability across regions was not related to measurement reliability. Heritability estimates exhibit a symmetric pattern across left and right hemispheres and are consistent in females and males. Our main findings in UK Biobank are consistent with those in Alzheimers Disease Neuroimaging Initiative (n ~ 1100), Philadelphia Neurodevelopmental Cohort (n ~ 600), and Pediatric Imaging, Neurocognition, and Genetics (n ~ 500) datasets, with more stable estimates in UK Biobank.

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