A bivariate mann-whitney approach for unraveling genetic variants and interactions contributing to comorbidity

Yalu Wen, Daniel J. Schaid, Qing Lu

Research output: Contribution to journalArticlepeer-review


Although comorbidity among complex diseases (e.g., drug dependence syndromes) is well documented, genetic variants contributing to the comorbidity are still largely unknown. The discovery of genetic variants and their interactions contributing to comorbidity will likely shed light on underlying pathophysiological and etiological processes, and promote effective treatments for comorbid conditions. For this reason, studies to discover genetic variants that foster the development of comorbidity represent high-priority research projects, as manifested in the behavioral genetics studies now underway. The yield from these studies can be enhanced by adopting novel statistical approaches, with the capacity of considering multiple genetic variants and possible interactions. For this purpose, we propose a bivariate Mann-Whitney (BMW) approach to unravel genetic variants and interactions contributing to comorbidity, as well as those unique to each comorbid condition. Through simulations, we found BMW outperformed two commonly adopted approaches in a variety of underlying disease and comorbidity models. We further applied BMW to datasets from the Study of Addiction: Genetics and Environment, investigating the contribution of 184 known nicotine dependence (ND) and alcohol dependence (AD) single nucleotide polymorphisms (SNPs) to the comorbidity of ND and AD. The analysis revealed a candidate SNP from CHRNA5, rs16969968, associated with both ND and AD, and replicated the findings in an independent dataset with a P-value of 1.06 × 10-03.

Original languageEnglish (US)
Pages (from-to)248-255
Number of pages8
JournalGenetic epidemiology
Issue number3
StatePublished - Apr 2013


  • Alcohol dependence
  • CHRNA5
  • Forward selection
  • High-order interaction
  • Nicotine dependence

ASJC Scopus subject areas

  • Epidemiology
  • Genetics(clinical)


Dive into the research topics of 'A bivariate mann-whitney approach for unraveling genetic variants and interactions contributing to comorbidity'. Together they form a unique fingerprint.

Cite this