The high-risk pedigree (HRP) is used to identify rare, highly penetrant, Mendelian-like, disease-related variants. However, for high genetic heterogeneity or complex traits disease, the effectiveness of HRPs will reduce. Researchers from USA and France cooperate to develop a new strategy combining high density SNP array and bioinformatics approach to analyze HRP. They sequenced 28 individuals from 11 pedigrees, and 2000 cases of multiple myeloma and unaffected controls to find two genes, USP45 (6q16, influencing DNA repair through endonuclease regulation) and ARID1A (1p36.11, a key gene in the SWI/SNF chromatin remodeling complex) highly suspected to cause multiple myeloma. The new method successfully identified more genes associated with rare and complex diseases.