TY - JOUR
T1 - Hearing function
T2 - Identification of new candidate genes further explaining the complexity of this sensory ability
AU - Concas, Maria Pina
AU - Morgan, Anna
AU - Serra, Fabrizio
AU - Nagtegaal, Andries Paul
AU - Oosterloo, Berthe C.
AU - Seshadri, Sudha
AU - Heard-Costa, Nancy
AU - Van Camp, Guy
AU - Fransen, Erik
AU - Francescatto, Margherita
AU - Logroscino, Giancarlo
AU - Sardone, Rodolfo
AU - Quaranta, Nicola
AU - Gasparini, Paolo
AU - Girotto, Giorgia
N1 - Funding Information:
This research was funded by: FVG-VBI-CAR: BENEFICENTIA Stiftung, D70-RESRICGIRO-TTO to GG and SENSAGING (D70-PRINSENSAGING-19: CUP J94I19000930006) to PG. SR: sponsors of Marco Polo scientific expedition 2010 and Ministry of Health RC 35/09 to PG. RS: funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. FHS: supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195, HHSN268201500001I, 75N92019D00031, and AG054076). This manuscript was not prepared in collaboration with investigators of the Framingham Heart Study and did not necessarily reflect the opinions or views of the Framingham Heart Study, Boston University, or NHLBI. SIA: funded by the Italian Ministry of Health with the “Ricerca Corrente 2019” Grant and under the Aging Network of Italian Research Hospitals (IRCCS).
Funding Information:
Funding: This research was funded by: FVG-VBI-CAR: BENEFICENTIA Stiftung, D70-RESRICGIRO-TTO to GG and SENSAGING (D70-PRINSENSAGING-19: CUP J94I19000930006) to PG. SR: sponsors of Marco Polo scientific expedition 2010 and Ministry of Health RC 35/09 to PG. RS: funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. FHS: supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with Boston University (Contract No. N01-HC-25195, HHSN268201500001I, 75N92019D00031, and AG054076). This manuscript was not
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021
Y1 - 2021
N2 - To date, the knowledge of the genetic determinants behind the modulation of hearing ability is relatively limited. To investigate this trait, we performed Genome-Wide Association Study (GWAS) meta-analysis using genotype and audiometric data (hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and pure-tone averages of thresholds at low, medium, and high frequencies) collected in nine cohorts from Europe, South-Eastern USA, Caucasus, and Central Asia, for an overall number of ~9000 subjects. Three hundred seventy-five genes across all nine analyses were tagged by single nucleotide polymorphisms (SNPs) reaching a suggestive p-value (p < 10−5 ). Amongst these, 15 were successfully replicated using a gene-based approach in the independent Italian Salus in the Apulia cohort (n = 1774) at the nominal significance threshold (p < 0.05). In addition, the expression level of the replicated genes was assessed in published human and mouse inner ear datasets. Considering expression patterns in humans and mice, eleven genes were considered particularly promising candidates for the hearing function: BNIP3L, ELP5, MAP3K20, MATN2, MTMR7, MYO1E, PCNT, R3HDM1, SLC9A9, TGFB2, and YTHDC2. These findings represent a further contribution to our understanding of the genetic basis of hearing function and its related diseases.
AB - To date, the knowledge of the genetic determinants behind the modulation of hearing ability is relatively limited. To investigate this trait, we performed Genome-Wide Association Study (GWAS) meta-analysis using genotype and audiometric data (hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and pure-tone averages of thresholds at low, medium, and high frequencies) collected in nine cohorts from Europe, South-Eastern USA, Caucasus, and Central Asia, for an overall number of ~9000 subjects. Three hundred seventy-five genes across all nine analyses were tagged by single nucleotide polymorphisms (SNPs) reaching a suggestive p-value (p < 10−5 ). Amongst these, 15 were successfully replicated using a gene-based approach in the independent Italian Salus in the Apulia cohort (n = 1774) at the nominal significance threshold (p < 0.05). In addition, the expression level of the replicated genes was assessed in published human and mouse inner ear datasets. Considering expression patterns in humans and mice, eleven genes were considered particularly promising candidates for the hearing function: BNIP3L, ELP5, MAP3K20, MATN2, MTMR7, MYO1E, PCNT, R3HDM1, SLC9A9, TGFB2, and YTHDC2. These findings represent a further contribution to our understanding of the genetic basis of hearing function and its related diseases.
KW - GWAS
KW - Gene expression
KW - Hearing
KW - Inner ear
KW - Meta-analysis
UR - http://www.scopus.com/inward/record.url?scp=85113185838&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85113185838&partnerID=8YFLogxK
U2 - 10.3390/genes12081228
DO - 10.3390/genes12081228
M3 - Article
C2 - 34440402
AN - SCOPUS:85113185838
VL - 12
JO - Genes
JF - Genes
SN - 2073-4425
IS - 8
M1 - 1228
ER -