Hearing function: Identification of new candidate genes further explaining the complexity of this sensory ability

Maria Pina Concas; Anna Morgan; Fabrizio Serra; Andries Paul Nagtegaal; Berthe C. Oosterloo; Sudha Seshadri; Nancy Heard-Costa; Guy Van Camp; Erik Fransen; Margherita Francescatto; Giancarlo Logroscino; Rodolfo Sardone; Nicola Quaranta; Paolo Gasparini; Giorgia Girotto

doi:10.3390/genes12081228

Hearing function: Identification of new candidate genes further explaining the complexity of this sensory ability

Maria Pina Concas^*
, Anna Morgan
, Fabrizio Serra
, Andries Paul Nagtegaal
, Berthe C. Oosterloo
, Sudha Seshadri
, Nancy Heard-Costa
, Guy Van Camp
, Erik Fransen
, Margherita Francescatto
, Giancarlo Logroscino
, Rodolfo Sardone
, Nicola Quaranta
, Paolo Gasparini
, Giorgia Girotto

^*Corresponding author for this work

Otorhinolaryngology and Head and Neck Surgery

IRCCS Ospedale Infantile Burlo Garofolo - Trieste
The Framingham Heart Study
University of Texas Health Science Center at San Antonio
Boston University School of Medicine
University of Antwerp
University of Trieste
University of Bari Aldo Moro
IRCCS Ente Ospedaliero specializzato in gastroenterologia Saverio De Bellis - Castellana Grotte (BA)

Research output: Contribution to journal › Article › Academic › peer-review

5 Citations (Scopus)

28 Downloads (Pure)

Abstract

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.

Original language	English
Article number	1228
Journal	Genes
Volume	12
Issue number	8
DOIs	https://doi.org/10.3390/genes12081228
Publication status	Published - 10 Aug 2021

Bibliographical note

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.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Access to Document

10.3390/genes12081228Licence: CC BY

Hearing Function Identification of New Candidate Genes Further Explaining the Complexity of This Sensory AbilityFinal published version, 1.01 MBLicence: CC BY

Cite this

Concas, M. P., Morgan, A., Serra, F., Nagtegaal, A. P., Oosterloo, B. C., Seshadri, S., Heard-Costa, N., Van Camp, G., Fransen, E., Francescatto, M., Logroscino, G., Sardone, R., Quaranta, N., Gasparini, P., & Girotto, G. (2021). Hearing function: Identification of new candidate genes further explaining the complexity of this sensory ability. Genes, 12(8), Article 1228. https://doi.org/10.3390/genes12081228

@article{2dd878af88b24c89a361652ac4b0956f,

title = "Hearing function: Identification of new candidate genes further explaining the complexity of this sensory ability",

abstract = "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 \textasciitilde{}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.",

author = "Concas, \{Maria Pina\} and Anna Morgan and Fabrizio Serra and Nagtegaal, \{Andries Paul\} and Oosterloo, \{Berthe C.\} and Sudha Seshadri and Nancy Heard-Costa and \{Van Camp\}, Guy and Erik Fransen and Margherita Francescatto and Giancarlo Logroscino and Rodolfo Sardone and Nicola Quaranta and Paolo Gasparini and Giorgia Girotto",

note = "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: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = aug,

day = "10",

doi = "10.3390/genes12081228",

language = "English",

volume = "12",

journal = "Genes",

issn = "2073-4425",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "8",

}

Concas, MP, Morgan, A, Serra, F, Nagtegaal, AP, Oosterloo, BC, Seshadri, S, Heard-Costa, N, Van Camp, G, Fransen, E, Francescatto, M, Logroscino, G, Sardone, R, Quaranta, N, Gasparini, P & Girotto, G 2021, 'Hearing function: Identification of new candidate genes further explaining the complexity of this sensory ability', Genes, vol. 12, no. 8, 1228. https://doi.org/10.3390/genes12081228

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 - 2021/8/10

Y1 - 2021/8/10

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.

UR - https://www.scopus.com/pages/publications/85113185838

U2 - 10.3390/genes12081228

DO - 10.3390/genes12081228

M3 - Article

C2 - 34440402

AN - SCOPUS:85113185838

SN - 2073-4425

VL - 12

JO - Genes

JF - Genes

IS - 8

M1 - 1228

ER -

Hearing function: Identification of new candidate genes further explaining the complexity of this sensory ability

Abstract

Bibliographical note

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this