Authors
Yanni Zeng, Pau Navarro, Ana M Fernandez-Pujals, Lynsey S Hall, Toni-Kim Clarke, Pippa A Thomson, Blair H Smith, Lynne J Hocking, Sandosh Padmanabhan, Caroline Hayward, Donald J MacIntyre, Naomi R Wray, Ian J Deary, David J Porteous, Chris S Haley, Andrew M McIntosh
Publication date
2017/2/15
Journal
Biological psychiatry
Volume
81
Issue
4
Pages
336-346
Publisher
Elsevier
Description
Background
Genome-wide association studies (GWASs) of major depressive disorder (MDD) have identified few significant associations. Testing the aggregation of genetic variants, in particular biological pathways, may be more powerful. Regional heritability analysis can be used to detect genomic regions that contribute to disease risk.
Methods
We integrated pathway analysis and multilevel regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS samples [Generation Scotland: The Scottish Family Health Study (GS:SFHS, N = 6455) and Psychiatric Genomics Consortium (PGC:MDD) (N = 18,759)]. A polygenic risk score (PRS) composed of single nucleotide polymorphisms from the pathway most consistently associated with MDD was created, and its accuracy to predict MDD, using area under the curve, logistic regression, and …
Scholar articles
Y Zeng, P Navarro, AM Fernandez-Pujals, LS Hall… - Biological psychiatry, 2017