Insights into complex trait etiology through rare variant aggregate association testing: implementing sequence and imputed data
Il 29/05/2025 ore 14.30 - 16.30
Area di Ricerca Napoli 1 - Conference Room
Via Pietro Castellino 111
Napoli
Semina hel by prof. Suzanne M. Leal PHD, Columbia University- Dept of Neurology.
Abstract
Rare-variant (RV) aggregate association analysis (AAA) can increase the power to detect associations compared to analyzing individual variants. The utility and caveats of performing RVAAA is demonstrated through a study of age-related (AR) hearing loss (HL) which analyzed UK Biobank exome sequence data and self-reported HL phenotypes. The study brings new insights into the etiology of ARHL, demonstrating many Mendelian genes, i.e., 32, which have been implicated in early onset HL also play a role in the etiology of ARHL. Additionally, RV in Mendelian HL genes typically exhibited higher effect sizes for ARHL compared to those in other associated genes.
To date RVAAA has been performed by analyzing sequence data, however generating these data for well powered complex trait studies can be prohibitively costly. Using imputation, many variants including RVs can be computationally generated. To investigate performing RVAAA using imputed variants, variants were imputed for UK Biobank study subjects who have exome sequence and genotype array data using the HRC_r1.1 (N=64,976 Haplotypes) and TOPMed_r3 (N=267,194 haplotypes) reference panels. Simulation studies were used to evaluate the power of performing RVAAA using imputed variants and the results compared to analyzing exome sequence data. Lipid levels were also analyzed, performing RVAAA using exome sequence data and imputed variants obtained from the UK Biobank. Even when ultra-RVs were analyzed, significant associations for the imputed variants could be detected, e.g. for PCSK9. Although, there is a decrease in power when performing RVAAA using imputed variants compared to analyzing sequence data it still a viable approach to detect complex trait associations.
Organizzato da:
Istituto di Biochimica e Biologia cellulare
Referente organizzativo:
Emilia Vitale
CNR - Dipartimento Scienze biomediche
Area di Ricerca Napoli 1
Via Pietro Castellino 111
Napoli
emilia.vitale@cnr.it
Modalità di accesso: ingresso libero
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