TABLE 2.
Application of LCL models to pharmacogenomics
| LCL-Based Model | Genetic Approach | Endophenotype | Phenotype | Reference |
|---|---|---|---|---|
| Pregenomic era (before 2003) | ||||
| Patients with HNSCC and unaffected family members | Heritability | Drug sensitivity | Cloos et al., 1999 | |
| Patients with MS and unaffected family members | Heritability | Sensitivity to ionizing radiation | Gipps and Kidson, 1984 | |
| Patients with Wilms' tumor | Candidate gene | Drug sensitivity | Imray et al., 1984 | |
| Patients with Werner syndrome | Candidate gene | Drug sensitivity | Poot et al., 1999 | |
| Postgenomic era (2003 to present) | ||||
| CEPH Pedigrees | Heritability, linkage analysis | Expression | Morley et al., 2004 | |
| HapMap trios | eQTL | Expression | Cheung et al., 2005; Stranger et al., 2005; Spielman et al., 2007; Storey et al., 2007; Stranger et al., 2007a,b; Duan et al., 2008; Huang et al., 2008d; Zhang et al., 2008, 2009; Kudaravalli et al., 2009 | |
| CEPH Pedigrees | Heritability, linkage analysis | Drug sensitivity | Dolan et al., 2004; Watters et al., 2004 | |
| CEPH Pedigrees/HapMap trios | Heritability, linkage-directed association studies | Drug sensitivity | Duan et al., 2007; Shukla et al., 2008, 2009; Bleibel et al., 2009 | |
| CEPH pedigrees | Linkage analysis, association studies | Expression | Response to ionizing radiation | Smirnov et al., 2009 |
| Human Variation Panel | Transcriptional profiling | Drug sensitivity | Li et al., 2008 | |
| Patients with breast cancer, with and without BRCA1/2 mutations | Transcriptional profiling | Response to ionizing radiation | Waddell et al., 2008 | |
| HapMap trios | Transcriptional profiling | Drug sensitivity | Fry et al., 2008 | |
| Subjects with HNSCC and control subjects | Transcriptional profiling | Drug sensitivity | Cloos et al., 2006 | |
| SOPHIE population | Candidate gene | Allelic imbalance | Urban et al., 2006; Tahara et al., 2009 | |
| Polymorphism Discovery Resource | Candidate gene | Allelic imbalance | Poonkuzhali et al., 2008 | |
| HapMap trios | Candidate gene | Allelic imbalance | Johnson et al., 2008 | |
| Subjects with type 2 diabetes and control subjects | Candidate gene | Allelic imbalance | Elbein et al., 2007 | |
| HapMap trios | Candidate gene | Drug sensitivity | Hartford et al., 2009 | |
| Human Variation Panel | Candidate gene | Drug sensitivity | Wang et al., 2008 | |
| Human Variation Panel/CEPH unrelateds | Candidate gene | Drug sensitivity | Innocenti et al., 2009 | |
| Schizophrenia case-control study | Candidate gene | Expression | Chagnon et al., 2008 | |
| HapMap trios | GWAS | Expression | Drug sensitivity | Huang et al., 2007a,b, 2008b,c,; Hartford et al., 2009 |
HNSCC, head and neck squamous cell carcinoma; MS, multiple sclerosis.