BUHMBOX: Distinguishing pleiotropy and heterogeneity
BUHMBOX is a tool to distinguish pleiotropy and heterogeneitiy. Suppose that we collect disease A cases. Then we observe that known disease B risk alleles are enriched within disease A cases. Is this because disease A and B have pleiotropy, or because disease A patients have a subset that shows genetic characteristics of disease B? BUHMBOX (Breaking Up Heterogeneous Mixture Based On Cross-locus correlations) is a tool to distinguish these two situations.
The intuition under BUHMBOX is that we will observe weak positive correlations between disease-B-loci in disease A cases, if it were due to heterogeneity, because of the subgrouping. Thus BUHMBOX aggregrates the correlations into one statistic. To strictly control for false positives, BUHMBOX uses pruning, PCs, and comparison to controls.
- Download: BUHMBOX v0.38 (R script) <--- right click and download
- Download: BUHMBOX power calculation code (R script) <--- right click and download
- Manual: BUHMBOX
- Manual: BUHMBOX Power calculation
Buhm HanÂ¶*, Jennie G Pouget*, Kamil Slowikowski, Eli Stahl, Cue Hyunkyu Lee, Dorothee Diogo, Xinli Hu, Yu Rang Park, Eunji Kim, Peter K Gregersen, Solbritt RantapĂ¤Ă¤ Dahlqvist, Jane Worthington, Javier Martin, Steve Eyre, Lars Klareskog, Tom Huizinga, Wei-Min Chen, Suna Onengut-Gumuscu, Stephen S Rich, Major Depressive Disorder Working Group of the Psychiatric Genomics Consortium, Naomi R Wray, Soumya RaychaudhuriÂ¶ "A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases." Nature Genetics. In Press doi:10.1038/ng.3572
Also was at Biorxiv: http://biorxiv.org/content/early/2015/11/06/030783
You can contact us at buhmhan AT amc DOT seoul DOT kr