@article{210eed4617a24ec8961f7ceda1e4a92f,
title = "Polygenic risk and white matter integrity in individuals at high risk of mood disorder",
abstract = "Background: Bipolar disorder (BD) and major depressive disorder (MDD) are highly heritable and genetically overlapping conditions characterized by episodic elevation and/or depression of mood. Both demonstrate abnormalities in white matter integrity, measured with diffusion tensor magnetic resonance imaging, that are also heritable. However, it is unclear how these abnormalities relate to the underlying genetic architecture of each disorder. Genome-wide association studies have demonstrated a significant polygenic contribution to BD and MDD, where risk is attributed to the summation of many alleles of small effect. Determining the effects of an overall polygenic risk profile score on neuroimaging abnormalities might help to identify proxy measures of genetic susceptibility and thereby inform models of risk prediction. Methods: In the current study, we determined the extent to which common genetic variation underlying risk to mood disorders (BD and MDD) was related to fractional anisotropy, an index of white matter integrity. This was conducted in unaffected individuals at familial risk of mood disorder (n = 70) and comparison subjects (n = 62). Polygenic risk scores were calculated separately for BD and MDD on the basis of genome-wide association study data from the Psychiatric GWAS Consortia. Results: We report that a higher polygenic risk allele load for MDD was significantly associated with decreased white matter integrity across both groups in a large cluster, with a peak in the right-sided superior longitudinal fasciculus. Conclusions: These findings suggest that the polygenic approach to examining brain imaging data might be a useful means of identifying traits linked to the genetic risk of mood disorders.",
keywords = "Bipolar disorder, diffusion tensor MRI, major depressive disorder, mood disorder, polygenic, white matter",
author = "Whalley, {Heather C.} and Emma Sprooten and Suzanna Hackett and Lynsey Hall and Blackwood, {Douglas H.} and Glahn, {David C.} and Mark Bastin and Jeremy Hall and Lawrie, {Stephen M.} and Sussmann, {Jessika E.} and McIntosh, {Andrew M.}",
note = "Funding Information: This study was conducted at the Brain Research Imaging Centre ( http://www.bric.ed.ac.uk ), which is supported by SINAPSE (Scottish Imaging Network, a Platform for Scientific Excellence; http://www.sinapse.ac.uk ). Funding Information: HCW is supported by a Dorothy Hodgkin Fellowship from the Royal Society (DH080018). JH is supported by a Scottish Senior Clinical Fellowship. JES is supported by a Clinical Research Training Fellowship from the Wellcome Trust. AMM was supported by the Health Foundation through a Clinician Scientist Fellowship (Ref: 2268/4295), by the Brain and Behaviour Research Foundation through a Brain & Behavior Research Foundation Independent Investigator Award, and by a Scottish Funding Council Senior Clinical Fellowship. HCW, ES, JH, SML, and AMM have received financial support from Pfizer (formerly Wyeth) in relation to imaging studies of people with schizophrenia and bipolar disorder. SML and AMM have done consultancy work for Roche Pharmaceuticals in connection with a possible new treatment for schizophrenia. SML has also received honoraria for lectures, chairing meetings, and consultancy work from Janssen in connection with brain imaging and therapeutic initiatives for psychosis. SH, LH, DHB, DCG, MB, and JES report no biomedical financial interests or potential conflicts of interest. Funding Information: We acknowledge the financial support of National Health Service Research Scotland, through the Scottish Mental Health Research Network ( http://www.smhrn.org.uk ), who provided assistance with subject recruitment and cognitive assessments. All imaging aspects also received financial support from the Dr. Mortimer and Theresa Sackler Foundation. ",
year = "2013",
month = aug,
day = "15",
doi = "10.1016/j.biopsych.2013.01.027",
language = "English",
volume = "74",
pages = "280--286",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier Inc.",
number = "4",
}