Whole-genome analyses of whole-brain data: working within an expanded search space.

Nat Neurosci
Authors
Keywords
Abstract

Large-scale comparisons of patients and healthy controls have unearthed genetic risk factors associated with a range of neurological and psychiatric illnesses. Meanwhile, brain imaging studies are increasing in size and scope, revealing disease and genetic effects on brain structure and function, and implicating neural pathways and causal mechanisms. With the advent of global neuroimaging consortia, imaging studies are now well powered to discover genetic variants that reliably affect the brain. Genetic analyses of brain measures from tens of thousands of people are being extended to test genetic associations with signals at millions of locations in the brain, and connectome-wide, genome-wide scans can jointly screen brain circuits and genomes; these analyses and others present new statistical challenges. There is a growing need for the community to establish and enforce standards in this developing field to ensure robust findings. Here we discuss how neuroimagers and geneticists have formed alliances to discover how genetic factors affect the brain. The field is rapidly advancing with ultra-high-resolution imaging and whole-genome sequencing. We recommend a rigorous approach to neuroimaging genomics that capitalizes on its recent successes and ensures the reliability of future discoveries.

Year of Publication
2014
Journal
Nat Neurosci
Volume
17
Issue
6
Pages
791-800
Date Published
2014 Jun
ISSN
1546-1726
URL
DOI
10.1038/nn.3718
PubMed ID
24866045
PubMed Central ID
PMC4300949
Links
Grant list
P41 EB015922 / EB / NIBIB NIH HHS / United States
MH094343 / MH / NIMH NIH HHS / United States
MH097268 / MH / NIMH NIH HHS / United States
MH089722 / MH / NIMH NIH HHS / United States
R01 AG040060 / AG / NIA NIH HHS / United States
R01 MH094343 / MH / NIMH NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
EB008432 / EB / NIBIB NIH HHS / United States
U54 EB020403 / EB / NIBIB NIH HHS / United States
R01 EB008432 / EB / NIBIB NIH HHS / United States
NS080655 / NS / NINDS NIH HHS / United States
MH085667 / MH / NIMH NIH HHS / United States
R01 MH089722 / MH / NIMH NIH HHS / United States
R01 NS080655 / NS / NINDS NIH HHS / United States
R01 MH097268 / MH / NIMH NIH HHS / United States
R01 MH101244 / MH / NIMH NIH HHS / United States
AG040060 / AG / NIA NIH HHS / United States
R01 MH085667 / MH / NIMH NIH HHS / United States