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This lecture discusses the common disease - common variant hypothesis versus the role of low-frequency, high-penetrance variants in complex traits. It covers the discovery of disease variants using GWAS and targeted sequencing, emphasizing the need for large populations. The lecture also explores the significance of odds ratios and the challenges in identifying causal variants. Additionally, it delves into whole genome association studies, P-values, Bonferroni correction, and the concept of 'missing heritability' in genetic studies.