Pleiotropy in complex traits: challenges and strategies

Abstract

Genome-wide association studies have identified many variants that each affects multiple traits, particularly across autoimmune diseases, cancers and neuropsychiatric disorders, suggesting that pleiotropic effects on human complex traits may be widespread. However, systematic detection of such effects is challenging and requires new methodologies and frameworks for interpreting cross-phenotype results. In this Review, we discuss the evidence for pleiotropy in contemporary genetic mapping studies, new and established analytical approaches to identifying pleiotropic effects, sources of spurious cross-phenotype effects and study design considerations. We also outline the molecular and clinical implications of such findings and discuss future directions of research.

Leveraging Multi-ethnic Evidence for Risk Assessment of Quantitative Traits in Minority Populations

“…Recent studies have demonstrated widespread pleiotropy: genetic loci that simultaneously influence related and sometimes seemingly unrelated traits. 34 Integrating pleiotropic information to jointly predict related traits has shown promise. 35 Extending XP-BLUP to leverage both trans-ethnic and cross-trait information may be particularly useful for under-studied traits.…”

Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene

“…Such pleiotropic effects have been demonstrated across several psychiatric disorders (Solovieff et al, 2013). For example, a recent study that examined schizophrenia (SCZ), bipolar disorder (BPD), MDD, and attention-deficit/hyperactivity disorder (ADHD) found that SNP-based heritability ranged from 17 to 29% within disorders.…”

Identification of pleiotropic genes and gene sets underlying growth and immunity traits: a case study on Meishan pigs

“…The former is known as biological pleiotropy, whereas the latter is a type of spurious pleiotropy (Solovieff et al, 2013). In this study, we investigated the genetic background of relationships between immunity and growth not only from the view of biological pleiotropy and spurious pleiotropy but also with the idea that genes that are involved in the same pathway could interact with one another, which can be regarded as another type of pleiotropy -namely, mediated pleiotropy (as reviewed by Solovieff et al, 2013).…”