TY - JOUR
T1 - Population-scale analysis of common and rare genetic variation associated with hearing loss in adults
AU - GHS-REGN DiscovEHR collaboration
AU - Regeneron Genetics Center
AU - Research Program Management
AU - Translational and Analytical Genetics
AU - Clinical Informatics
AU - Genome Informatics
AU - Sequencing and Lab Operations
AU - RGC Management and Leadership Team
AU - Decibel-REGN collaboration
AU - Program Management & Alliance Management
AU - Collaboration Core Team
AU - Praveen, Kavita
AU - Dobbyn, Lee
AU - Gurski, Lauren
AU - Ayer, Ariane H.
AU - Staples, Jeffrey
AU - Mishra, Shawn
AU - Bai, Yu
AU - Kaufman, Alexandra
AU - Moscati, Arden
AU - Benner, Christian
AU - Chen, Esteban
AU - Chen, Siying
AU - Popov, Alexander
AU - Smith, Janell
AU - Williams, Marc
AU - Wagner, Jen
AU - Sturm, Amy
AU - Strande, Natasha
AU - Still, Christopher
AU - Person, Thomas Nate
AU - Oetjens, Matthew
AU - Mirshahi, Tooraj
AU - Meyer, Michelle
AU - Metpally, Raghu P.
AU - Martin, Christa L.
AU - Manus, J. Neil
AU - Ledbetter, David H.
AU - Leader, Joseph B.
AU - Kirchner, H. Lester
AU - Kelly, Melissa
AU - Hartzel, Dustin N.
AU - Davis, F. Daniel
AU - Colonie, Ryan D.
AU - Carey, David J.
AU - Buchanan, Adam
AU - Boris, Derek
AU - Bodian, Dale
AU - Blank, Jackie
AU - Adams, Lance J.
AU - Mitnaul, Lyndon J.
AU - LeBlanc, Michelle G.
AU - Mighty, Jason
AU - Gelfman, Sahar
AU - Di Gioia, Alessandro
AU - Yadav, Ashish
AU - Sharma, Deepika
AU - Li, Dadong
AU - Cantor, Michael
AU - Banerjee, Nilanjana
AU - Staples, Jeffrey C.
N1 - Publisher Copyright:
© The Author(s) 2022.
PY - 2022/12
Y1 - 2022/12
N2 - To better understand the genetics of hearing loss, we performed a genome-wide association meta-analysis with 125,749 cases and 469,497 controls across five cohorts. We identified 53/c loci affecting hearing loss risk, including common coding variants in COL9A3 and TMPRSS3. Through exome sequencing of 108,415 cases and 329,581 controls, we observed rare coding associations with 11 Mendelian hearing loss genes, including additive effects in known hearing loss genes GJB2 (Gly12fs; odds ratio [OR] = 1.21, P = 4.2 × 10−11) and SLC26A5 (gene burden; OR = 1.96, P = 2.8 × 10−17). We also identified hearing loss associations with rare coding variants in FSCN2 (OR = 1.14, P = 1.9 × 10−15) and KLHDC7B (OR = 2.14, P = 5.2 × 10−30). Our results suggest a shared etiology between Mendelian and common hearing loss in adults. This work illustrates the potential of large-scale exome sequencing to elucidate the genetic architecture of common disorders where both common and rare variation contribute to risk.
AB - To better understand the genetics of hearing loss, we performed a genome-wide association meta-analysis with 125,749 cases and 469,497 controls across five cohorts. We identified 53/c loci affecting hearing loss risk, including common coding variants in COL9A3 and TMPRSS3. Through exome sequencing of 108,415 cases and 329,581 controls, we observed rare coding associations with 11 Mendelian hearing loss genes, including additive effects in known hearing loss genes GJB2 (Gly12fs; odds ratio [OR] = 1.21, P = 4.2 × 10−11) and SLC26A5 (gene burden; OR = 1.96, P = 2.8 × 10−17). We also identified hearing loss associations with rare coding variants in FSCN2 (OR = 1.14, P = 1.9 × 10−15) and KLHDC7B (OR = 2.14, P = 5.2 × 10−30). Our results suggest a shared etiology between Mendelian and common hearing loss in adults. This work illustrates the potential of large-scale exome sequencing to elucidate the genetic architecture of common disorders where both common and rare variation contribute to risk.
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U2 - 10.1038/s42003-022-03408-7
DO - 10.1038/s42003-022-03408-7
M3 - Article
C2 - 35661827
AN - SCOPUS:85131701650
SN - 2399-3642
VL - 5
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 540
ER -