Multi-omic studies on missense PLG variants in families with otitis media.
Author
Bootpetch, Tori CHafrén, Lena
Elling, Christina L
Baschal, Erin E
Manichaikul, Ani W
Pine, Harold S
Szeremeta, Wasyl
Scholes, Melissa A
Cass, Stephen P
Larson, Eric D
Chan, Kenny H
Ishaq, Rafaqat
Prager, Jeremy D
Shaikh, Rehan S
Gubbels, Samuel P
Yousaf, Ayesha
Wine, Todd M
Bamshad, Michael J
Yoon, Patricia J
Jenkins, Herman A
Nickerson, Deborah A
Streubel, Sven-Olrik
Friedman, Norman R
Frank, Daniel N
Einarsdottir, Elisabet
Kere, Juha
Riazuddin, Saima
Daly, Kathleen A
Leal, Suzanne M
Ryan, Allen F
Mattila, Petri S
Ahmed, Zubair M
Sale, Michele M
Chonmaitree, Tasnee
Santos-Cortez, Regie Lyn P
Date
2020-09-14Journal
Scientific ReportsPublisher
Springer NatureType
Article
Metadata
Show full item recordAbstract
Otitis media (OM), a very common disease in young children, can result in hearing loss. In order to potentially replicate previously reported associations between OM and PLG, exome and Sanger sequencing, RNA-sequencing of saliva and middle ear samples, 16S rRNA sequencing, molecular modeling, and statistical analyses including transmission disequilibrium tests (TDT) were performed in a multi-ethnic cohort of 718 families and simplex cases with OM. We identified four rare PLG variants c.112A > G (p.Lys38Glu), c.782G > A (p.Arg261His), c.1481C > T (p.Ala494Val) and c.2045 T > A (p.Ile682Asn), and one common variant c.1414G > A (p.Asp472Asn). However TDT analyses for these PLG variants did not demonstrate association with OM in 314 families. Additionally PLG expression is very low or absent in normal or diseased middle ear in mouse and human, and salivary expression and microbial α-diversity were non-significant in c.1414G > A (p.Asp472Asn) carriers. Based on molecular modeling, the novel rare variants particularly c.782G > A (p.Arg261His) and c.2045 T > A (p.Ile682Asn) were predicted to affect protein structure. Exploration of other potential disease mechanisms will help elucidate how PLG contributes to OM susceptibility in humans. Our results underline the importance of following up findings from genome-wide association through replication studies, preferably using multi-omic datasets.Identifier to cite or link to this item
http://hdl.handle.net/10713/13774ae974a485f413a2113503eed53cd6c53
10.1038/s41598-020-70498-w
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