Skip to main content
Top
Published in: Journal of the Association for Research in Otolaryngology 6/2023

30-11-2023 | Original Article

Genome-Wide Association Study of Chronic Dizziness in the Elderly Identifies Loci Implicating MLLT10, BPTF, LINC01224, and ROS1

Authors: Royce Clifford, Daniel Munro, Daniel Dochtermann, Poornima Devineni, Saiju Pyarajan, Francesca Telese, Abraham A. Palmer, Pejman Mohammadi, Rick Friedman, Million Veteran Program

Published in: Journal of the Association for Research in Otolaryngology | Issue 6/2023

Login to get access

Abstract

Purpose

Chronic age-related imbalance is a common cause of falls and subsequent death in the elderly and can arise from dysfunction of the vestibular system, an elegant neuroanatomical group of pathways that mediates human perception of acceleration, gravity, and angular head motion. Studies indicate that 27–46% of the risk of age-related chronic imbalance is genetic; nevertheless, the underlying genes remain unknown.

Methods

The cohort consisted of 50,339 cases and 366,900 controls in the Million Veteran Program. The phenotype comprised cases with two ICD diagnoses of vertigo or dizziness at least 6 months apart, excluding acute or recurrent vertiginous syndromes and other non-vestibular disorders. Genome-wide association studies were performed as individual logistic regressions on European, African American, and Hispanic ancestries followed by trans-ancestry meta-analysis. Downstream analysis included case-case-GWAS, fine mapping, probabilistic colocalization of significant variants and genes with eQTLs, and functional analysis of significant hits.

Results

Two significant loci were identified in Europeans, another in the Hispanic population, and two additional in trans-ancestry meta-analysis, including three novel loci. Fine mapping revealed credible sets of intronic single nucleotide polymorphisms (SNPs) in MLLT10 - a histone methyl transferase cofactor, BPTF - a subunit of a nucleosome remodeling complex implicated in neurodevelopment, and LINC01224 - a proto-oncogene receptor tyrosine kinase.

Conclusion

Despite the difficulties of phenotyping the nature of chronic imbalance, we replicated two loci from previous vertigo GWAS studies and identified three novel loci. Findings suggest candidates for further study and ultimate treatment of this common elderly disorder.
Appendix
Available only for authorised users
Literature
3.
go back to reference Kippenbrock T, Soja ME (2007) Preventing falls in the elderly: interviewing patients who have fallen. Researchers attempt to identify fall-risk factors from the patients’ point of view. Geriatr Nurs 14:205–9 Kippenbrock T, Soja ME (2007) Preventing falls in the elderly: interviewing patients who have fallen. Researchers attempt to identify fall-risk factors from the patients’ point of view. Geriatr Nurs 14:205–9
5.
go back to reference Cutson TM (1994) Falls in the elderly. Am Fam Physician 49:149–156PubMed Cutson TM (1994) Falls in the elderly. Am Fam Physician 49:149–156PubMed
6.
go back to reference Teixeira AR, Wender MH, Gonçalves AK, Freitas CDLR, dos Santos AMPV, Soldera CLC (2016) Dizziness, physical exercise, falls, and depression in adults and the elderly. Int Arch Otorhinolaryngol 20:124–131PubMed Teixeira AR, Wender MH, Gonçalves AK, Freitas CDLR, dos Santos AMPV, Soldera CLC (2016) Dizziness, physical exercise, falls, and depression in adults and the elderly. Int Arch Otorhinolaryngol 20:124–131PubMed
7.
go back to reference Mitchell AJ, Vaze A, Rao S (2009) Clinical diagnosis of depression in primary care: a meta-analysis. Lancet 374:609–619PubMed Mitchell AJ, Vaze A, Rao S (2009) Clinical diagnosis of depression in primary care: a meta-analysis. Lancet 374:609–619PubMed
8.
go back to reference Furman JM, Redfern MS (2001) Effect of aging on the otolith-ocular reflex. J Vestib Res 11:91–103PubMed Furman JM, Redfern MS (2001) Effect of aging on the otolith-ocular reflex. J Vestib Res 11:91–103PubMed
9.
go back to reference Baloh RW, Jacobson KM, Socotch TM (1993) The effect of aging on visual-vestibuloocular responses. Exp Brain Res 95:509–516PubMed Baloh RW, Jacobson KM, Socotch TM (1993) The effect of aging on visual-vestibuloocular responses. Exp Brain Res 95:509–516PubMed
10.
go back to reference Matheson AJ, Darlington CL, Smith PF (1999) Further evidence for age-related deficits in human postural function. J Vestib Res 9:261–264PubMed Matheson AJ, Darlington CL, Smith PF (1999) Further evidence for age-related deficits in human postural function. J Vestib Res 9:261–264PubMed
11.
go back to reference Rauch SD, Velazquez-Villaseñor L, Dimitri PS, Merchant SN (2001) Decreasing hair cell counts in aging humans. Ann N Y Acad Sci 942:220–227PubMed Rauch SD, Velazquez-Villaseñor L, Dimitri PS, Merchant SN (2001) Decreasing hair cell counts in aging humans. Ann N Y Acad Sci 942:220–227PubMed
12.
go back to reference Jang YS, Hwang CH, Shin JY, Bae WY, Kim LS (2006) Age-related changes on the morphology of the otoconia. Laryngoscope 116:996–1001PubMed Jang YS, Hwang CH, Shin JY, Bae WY, Kim LS (2006) Age-related changes on the morphology of the otoconia. Laryngoscope 116:996–1001PubMed
13.
go back to reference Walther LE, Westhofen M (2007) Presbyvertigo-aging of otoconia and vestibular sensory cells. J Vestib Res 17:89–92PubMed Walther LE, Westhofen M (2007) Presbyvertigo-aging of otoconia and vestibular sensory cells. J Vestib Res 17:89–92PubMed
14.
go back to reference Maes L, Dhooge I, D’haenens W, Bockstael A, Keppler H, Philips B, Swinnen F, Vinck BM (2010) The effect of age on the sinusoidal harmonic acceleration test, pseudorandom rotation test, velocity step test, caloric test, and vestibular-evoked myogenic potential test. Ear Hear 31:84–94 Maes L, Dhooge I, D’haenens W, Bockstael A, Keppler H, Philips B, Swinnen F, Vinck BM (2010) The effect of age on the sinusoidal harmonic acceleration test, pseudorandom rotation test, velocity step test, caloric test, and vestibular-evoked myogenic potential test. Ear Hear 31:84–94
16.
go back to reference Wagner H, Melhus H, Pedersen NL, Michaëlsson K (2009) Heritability of impaired balance: a nationwide cohort study in twins. Osteoporosis Int 20:577–583 Wagner H, Melhus H, Pedersen NL, Michaëlsson K (2009) Heritability of impaired balance: a nationwide cohort study in twins. Osteoporosis Int 20:577–583
17.
go back to reference El Haber N, Hill KD, Cassano A-MT, Paton LM, Macinnis RJ, Cui JS, Hopper JL, Wark JD (2006) Genetic and environmental influences on variation in balance performance among female twin pairs aged 21–82 years. Am J Epidemiol 164:246–56 El Haber N, Hill KD, Cassano A-MT, Paton LM, Macinnis RJ, Cui JS, Hopper JL, Wark JD (2006) Genetic and environmental influences on variation in balance performance among female twin pairs aged 21–82 years. Am J Epidemiol 164:246–56
18.
go back to reference Skuladottir ATh, Bjornsdottir G, Nawaz MS, Petersen H, Rognvaldsson S, Moore KHS, Olafsson PI, Magnusson SH, Bjornsdottir A, Sveinsson OA, Sigurdardottir GR, Saevarsdottir S, Ivarsdottir EV, Stefansdottir L, Gunnarsson B, Muhlestein JB, Knowlton KU, Jones DA, Nadauld LD, Hartmann AM, Rujescu D, Strupp M, Walters GB, Thorgeirsson TE, Jonsdottir I, Holm H, Thorleifsson G, Gudbjartsson DF, Sulem P, Stefansson H, Stefansson K (2021) A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo. Commun Biol 4:1148PubMedPubMedCentral Skuladottir ATh, Bjornsdottir G, Nawaz MS, Petersen H, Rognvaldsson S, Moore KHS, Olafsson PI, Magnusson SH, Bjornsdottir A, Sveinsson OA, Sigurdardottir GR, Saevarsdottir S, Ivarsdottir EV, Stefansdottir L, Gunnarsson B, Muhlestein JB, Knowlton KU, Jones DA, Nadauld LD, Hartmann AM, Rujescu D, Strupp M, Walters GB, Thorgeirsson TE, Jonsdottir I, Holm H, Thorleifsson G, Gudbjartsson DF, Sulem P, Stefansson H, Stefansson K (2021) A genome-wide meta-analysis uncovers six sequence variants conferring risk of vertigo. Commun Biol 4:1148PubMedPubMedCentral
19.
go back to reference Xiao AY, Tan ML, Plana MN, Yadav D, Zamora J, Petrov MS (2018) The use of international classification of diseases codes to identify patients with pancreatitis: a systematic review and meta-analysis of diagnostic accuracy studies. Clin Transl Gastroenterol 9. https://doi.org/10.1038/s41424-018-0060-1 Xiao AY, Tan ML, Plana MN, Yadav D, Zamora J, Petrov MS (2018) The use of international classification of diseases codes to identify patients with pancreatitis: a systematic review and meta-analysis of diagnostic accuracy studies. Clin Transl Gastroenterol 9. https://​doi.​org/​10.​1038/​s41424-018-0060-1
20.
go back to reference Foley HE, Knight JC, Ploughman M, Asghari S, Audas R (2020) Identifying cases of chronic pain using health administrative data: a validation study. Can J Pain 4:252–267PubMedPubMedCentral Foley HE, Knight JC, Ploughman M, Asghari S, Audas R (2020) Identifying cases of chronic pain using health administrative data: a validation study. Can J Pain 4:252–267PubMedPubMedCentral
21.
go back to reference Wassermann A, Finn S, Axer H (2022) Age-associated characteristics of patients with chronic dizziness and vertigo. J Geriatr Psychiatry Neurol 35:580–585PubMed Wassermann A, Finn S, Axer H (2022) Age-associated characteristics of patients with chronic dizziness and vertigo. J Geriatr Psychiatry Neurol 35:580–585PubMed
22.
go back to reference Müller KJ, Becker-Bense S, Strobl R, Grill E, Dieterich M (2022) Chronic vestibular syndromes in the elderly: presbyvestibulopathy—an isolated clinical entity? Eur J Neurol 29:1825–1835PubMed Müller KJ, Becker-Bense S, Strobl R, Grill E, Dieterich M (2022) Chronic vestibular syndromes in the elderly: presbyvestibulopathy—an isolated clinical entity? Eur J Neurol 29:1825–1835PubMed
24.
go back to reference Yetiser S (2020) Review of the pathology underlying benign paroxysmal positional vertigo. J Int Med Res 48:300060519892370PubMed Yetiser S (2020) Review of the pathology underlying benign paroxysmal positional vertigo. J Int Med Res 48:300060519892370PubMed
25.
go back to reference Fang H, Hui Q, Lynch J, Honerlaw J, Assimes TL, Huang J, Vujkovic M, Damrauer SM, Pyarajan S, Gaziano JM, DuVall SL, O’Donnell CJ, Cho K, Chang K-M, Wilson PWF, Tsao PS, Sun YV, Tang H, Gaziano JM, Ramoni R, Breeling J, Chang K-M, Huang G, Muralidhar S, O’Donnell CJ, Tsao PS, Muralidhar S, Moser J, Whitbourne SB, Brewer J V., Concato J, Warren S, Argyres DP, Stephens B, Brophy MT, Humphries DE, Do N, Shayan S, Nguyen X-MT, Pyarajan S, Cho K, Hauser E, Sun Y, Zhao H, Wilson P, McArdle R, Dellitalia L, Harley J, Whittle J, Beckham J, Wells J, Gutierrez S, Gibson G, Kaminsky L, Villareal G, Kinlay S, Xu J, Hamner M, Haddock KS, Bhushan S, Iruvanti P, Godschalk M, Ballas Z, Buford M, Mastorides S, Klein J, Ratcliffe N, Florez H, Swann A, Murdoch M, Sriram P, Yeh SS, Washburn R, Jhala D, Aguayo S, Cohen D, Sharma S, Callaghan J, Oursler KA, Whooley M, Ahuja S, Gutierrez A, Schifman R, Greco J, Rauchman M, Servatius R, Oehlert M, Wallbom A, Fernando R, Morgan T, Stapley T, Sherman S, Anderson G, Sonel E, Boyko E, Meyer L, Gupta S, Fayad J, Hung A, Lichy J, Hurley R, Robey B, Striker R (2019) Harmonizing genetic ancestry and self-identified race/ethnicity in genome-wide association studies. Am J Human Gen 105:763–72 Fang H, Hui Q, Lynch J, Honerlaw J, Assimes TL, Huang J, Vujkovic M, Damrauer SM, Pyarajan S, Gaziano JM, DuVall SL, O’Donnell CJ, Cho K, Chang K-M, Wilson PWF, Tsao PS, Sun YV, Tang H, Gaziano JM, Ramoni R, Breeling J, Chang K-M, Huang G, Muralidhar S, O’Donnell CJ, Tsao PS, Muralidhar S, Moser J, Whitbourne SB, Brewer J V., Concato J, Warren S, Argyres DP, Stephens B, Brophy MT, Humphries DE, Do N, Shayan S, Nguyen X-MT, Pyarajan S, Cho K, Hauser E, Sun Y, Zhao H, Wilson P, McArdle R, Dellitalia L, Harley J, Whittle J, Beckham J, Wells J, Gutierrez S, Gibson G, Kaminsky L, Villareal G, Kinlay S, Xu J, Hamner M, Haddock KS, Bhushan S, Iruvanti P, Godschalk M, Ballas Z, Buford M, Mastorides S, Klein J, Ratcliffe N, Florez H, Swann A, Murdoch M, Sriram P, Yeh SS, Washburn R, Jhala D, Aguayo S, Cohen D, Sharma S, Callaghan J, Oursler KA, Whooley M, Ahuja S, Gutierrez A, Schifman R, Greco J, Rauchman M, Servatius R, Oehlert M, Wallbom A, Fernando R, Morgan T, Stapley T, Sherman S, Anderson G, Sonel E, Boyko E, Meyer L, Gupta S, Fayad J, Hung A, Lichy J, Hurley R, Robey B, Striker R (2019) Harmonizing genetic ancestry and self-identified race/ethnicity in genome-wide association studies. Am J Human Gen 105:763–72
26.
go back to reference Hunter-Zinck H, Shi Y, Li M, Gorman BR, Ji SG, Sun N, Webster T, Liem A, Hsieh P, Devineni P, Karnam P, Gong X, Radhakrishnan L, Schmidt J, Assimes TL, Huang J, Pan C, Humphries D, Brophy M, Moser J, Muralidhar S, Huang GD, Przygodzki R, Concato J, Gaziano JM, Gelernter J, O’Donnell CJ, Hauser ER, Zhao H, O’Leary TJ, Tsao PS, Pyarajan S (2020) Genotyping array design and data quality control in the Million Veteran Program. Am J Hum Genet 106:535–548PubMedPubMedCentral Hunter-Zinck H, Shi Y, Li M, Gorman BR, Ji SG, Sun N, Webster T, Liem A, Hsieh P, Devineni P, Karnam P, Gong X, Radhakrishnan L, Schmidt J, Assimes TL, Huang J, Pan C, Humphries D, Brophy M, Moser J, Muralidhar S, Huang GD, Przygodzki R, Concato J, Gaziano JM, Gelernter J, O’Donnell CJ, Hauser ER, Zhao H, O’Leary TJ, Tsao PS, Pyarajan S (2020) Genotyping array design and data quality control in the Million Veteran Program. Am J Hum Genet 106:535–548PubMedPubMedCentral
27.
go back to reference Chang CC, Chow CC, Tellier LCAM, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4:1–16 Chang CC, Chow CC, Tellier LCAM, Vattikuti S, Purcell SM, Lee JJ (2015) Second-generation PLINK: rising to the challenge of larger and richer datasets. Gigascience 4:1–16
28.
go back to reference Zhou W, Nielsen JB, Fritsche LG, Dey R, Maiken E, Wolford BN, Lefaive J, Vandehaar P, Sarah A, Gifford A, Bastarache LA, Wei W, Denny JC, Hveem K, Kang HM, Abecasis GR, Willer CJ (2019) Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. Nat Genetics 50:1335–1341 Zhou W, Nielsen JB, Fritsche LG, Dey R, Maiken E, Wolford BN, Lefaive J, Vandehaar P, Sarah A, Gifford A, Bastarache LA, Wei W, Denny JC, Hveem K, Kang HM, Abecasis GR, Willer CJ (2019) Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies. Nat Genetics 50:1335–1341
29.
go back to reference Patterson N, Price AL, Reich D (2006) Population structure and eigenanalysis. PLoS Genet 2:190 Patterson N, Price AL, Reich D (2006) Population structure and eigenanalysis. PLoS Genet 2:190
30.
go back to reference Mbatchou J, Barnard L, Backman J, Marcketta A, Kosmicki JA, Ziyatdinov A, Benner C, O’Dushlaine C, Barber M, Boutkov B, Habegger L, Ferreira M, Baras A, Reid J, Abecasis G, Maxwell E, Marchini J (2021) Computationally efficient whole-genome regression for quantitative and binary traits. Nat Genet 53. https://doi.org/10.1038/s41588-021-00870-7 Mbatchou J, Barnard L, Backman J, Marcketta A, Kosmicki JA, Ziyatdinov A, Benner C, O’Dushlaine C, Barber M, Boutkov B, Habegger L, Ferreira M, Baras A, Reid J, Abecasis G, Maxwell E, Marchini J (2021) Computationally efficient whole-genome regression for quantitative and binary traits. Nat Genet 53. https://​doi.​org/​10.​1038/​s41588-021-00870-7
31.
go back to reference Willer CJ, Li Y, Abecasis GR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26:2190–2191PubMedPubMedCentral Willer CJ, Li Y, Abecasis GR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26:2190–2191PubMedPubMedCentral
32.
go back to reference Bulik-Sullivan BK, Loh P-R, Finucane HK, Ripke S, Yang J, Patterson N, Daly MJ, Price AL, Neale BM (2015) LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet 47:291–295PubMedPubMedCentral Bulik-Sullivan BK, Loh P-R, Finucane HK, Ripke S, Yang J, Patterson N, Daly MJ, Price AL, Neale BM (2015) LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat Genet 47:291–295PubMedPubMedCentral
34.
go back to reference Finucane, H, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y et al (2015) Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat Genet 47:1228–35 Finucane, H, Bulik-Sullivan B, Gusev A, Trynka G, Reshef Y et al (2015) Partitioning heritability by functional annotation using genome-wide association summary statistics. Nat Genet 47:1228–35
36.
go back to reference Clifford RE, Maihofer AX, Stein MB, Ryan AF, Nievergelt CM (2020) Novel risk loci in tinnitus and causal inference with neuropsychiatric disorders among adults of European ancestry. JAMA Otolaryngol Head Neck Surg 146:1015–1025PubMedPubMedCentral Clifford RE, Maihofer AX, Stein MB, Ryan AF, Nievergelt CM (2020) Novel risk loci in tinnitus and causal inference with neuropsychiatric disorders among adults of European ancestry. JAMA Otolaryngol Head Neck Surg 146:1015–1025PubMedPubMedCentral
37.
go back to reference Peyrot WJ, Price AL (2021) Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS. Nat Genet 53:445–454PubMedPubMedCentral Peyrot WJ, Price AL (2021) Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS. Nat Genet 53:445–454PubMedPubMedCentral
38.
go back to reference Hukku A, Pividori M, Luca F, Pique-Regi R, Im HK, Wen X (2021) Probabilistic colocalization of genetic variants from complex and molecular traits: promise and limitations. Am J Hum Genet 108:25–35PubMed Hukku A, Pividori M, Luca F, Pique-Regi R, Im HK, Wen X (2021) Probabilistic colocalization of genetic variants from complex and molecular traits: promise and limitations. Am J Hum Genet 108:25–35PubMed
40.
go back to reference GTEx Consortium (2020) The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science (1979) 369:1318–30 GTEx Consortium (2020) The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science (1979) 369:1318–30
44.
go back to reference Watanabe K, Taskesen E, van Bochoven A, Posthuma D (2017) Functional mapping and annotation of genetic associations with FUMA. Nat Commun 8:1826PubMedPubMedCentral Watanabe K, Taskesen E, van Bochoven A, Posthuma D (2017) Functional mapping and annotation of genetic associations with FUMA. Nat Commun 8:1826PubMedPubMedCentral
45.
go back to reference de Leeuw CA, Mooij JM, Heskes T, Posthuma D (2015) MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol 11:e1004219PubMedPubMedCentral de Leeuw CA, Mooij JM, Heskes T, Posthuma D (2015) MAGMA: generalized gene-set analysis of GWAS data. PLoS Comput Biol 11:e1004219PubMedPubMedCentral
47.
go back to reference Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J (1979) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 2009(326):289–293 Lieberman-Aiden E, van Berkum NL, Williams L, Imakaev M, Ragoczy T, Telling A, Amit I, Lajoie BR, Sabo PJ, Dorschner MO, Sandstrom R, Bernstein B, Bender MA, Groudine M, Gnirke A, Stamatoyannopoulos J, Mirny LA, Lander ES, Dekker J (1979) Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science 2009(326):289–293
48.
go back to reference Orvis J, Gottfried B, Kancherla J, Adkins RS, Song Y, Dror AA, Olley D, Rose K, Chrysostomou E, Kelly MC, Milon B, Matern MS, Azaiez H, Herb B, Colantuoni C, Carter RL, Ament SA, Kelley MW, White O, Bravo HC, Mahurkar A, Hertzano R (2021) gEAR: Gene Expression Analysis Resource portal for community-driven, multi-omic data exploration. Nat Methods 18:843–844PubMedPubMedCentral Orvis J, Gottfried B, Kancherla J, Adkins RS, Song Y, Dror AA, Olley D, Rose K, Chrysostomou E, Kelly MC, Milon B, Matern MS, Azaiez H, Herb B, Colantuoni C, Carter RL, Ament SA, Kelley MW, White O, Bravo HC, Mahurkar A, Hertzano R (2021) gEAR: Gene Expression Analysis Resource portal for community-driven, multi-omic data exploration. Nat Methods 18:843–844PubMedPubMedCentral
49.
go back to reference Watanabe K, Stringer S, Frei O, Umićević Mirkov M, de Leeuw C, Polderman TJC, van der Sluis S, Andreassen OA, Neale BM, Posthuma D (2019) A global overview of pleiotropy and genetic architecture in complex traits. Nat Genet 51:1339–1348PubMed Watanabe K, Stringer S, Frei O, Umićević Mirkov M, de Leeuw C, Polderman TJC, van der Sluis S, Andreassen OA, Neale BM, Posthuma D (2019) A global overview of pleiotropy and genetic architecture in complex traits. Nat Genet 51:1339–1348PubMed
50.
go back to reference Hromatka BS, Tung JY, Kiefer AK, Do CB, Hinds DA, Eriksson N (2015) Genetic variants associated with motion sickness point to roles for inner ear development, neurological processes and glucose homeostasis. Hum Mol Genet 24:2700–2708PubMedPubMedCentral Hromatka BS, Tung JY, Kiefer AK, Do CB, Hinds DA, Eriksson N (2015) Genetic variants associated with motion sickness point to roles for inner ear development, neurological processes and glucose homeostasis. Hum Mol Genet 24:2700–2708PubMedPubMedCentral
51.
go back to reference Rujescu D, Hartmann AM, Giegling I, Konte B, Herrling M, Himmelein S, Strupp M (2018) Genome-wide association study in vestibular neuritis: involvement of the host factor for HSV-1 replication. Front Neurol 9:1–9 Rujescu D, Hartmann AM, Giegling I, Konte B, Herrling M, Himmelein S, Strupp M (2018) Genome-wide association study in vestibular neuritis: involvement of the host factor for HSV-1 replication. Front Neurol 9:1–9
52.
go back to reference Strupp M, Maul S, Konte B, Hartmann AM, Giegling I, Wollenteit S, Feil K, Rujescu D (2020) A variation in FGF14 is associated with downbeat nystagmus in a genome-wide association study. Cerebellum 19:348–357PubMed Strupp M, Maul S, Konte B, Hartmann AM, Giegling I, Wollenteit S, Feil K, Rujescu D (2020) A variation in FGF14 is associated with downbeat nystagmus in a genome-wide association study. Cerebellum 19:348–357PubMed
53.
go back to reference Vietri Rudan M, Barrington C, Henderson S, Ernst C, Odom DT, Tanay A, Hadjur S (2015) Comparative Hi-C reveals that CTCF underlies evolution of chromosomal domain architecture. Cell Rep 10:1297–1309PubMedPubMedCentral Vietri Rudan M, Barrington C, Henderson S, Ernst C, Odom DT, Tanay A, Hadjur S (2015) Comparative Hi-C reveals that CTCF underlies evolution of chromosomal domain architecture. Cell Rep 10:1297–1309PubMedPubMedCentral
55.
go back to reference Rudnicki A, Isakov O, Ushakov K, Shivatzki S, Weiss I, Friedman LM, Shomron N, Avraham KB (2014) Next-generation sequencing of small RNAs from inner ear sensory epithelium identifies microRNAs and defines regulatory pathways. BMC Genomics 15:1–12 Rudnicki A, Isakov O, Ushakov K, Shivatzki S, Weiss I, Friedman LM, Shomron N, Avraham KB (2014) Next-generation sequencing of small RNAs from inner ear sensory epithelium identifies microRNAs and defines regulatory pathways. BMC Genomics 15:1–12
56.
go back to reference Shen J, Scheffer DI, Kwan KY, Corey DP (2015) SHIELD: an integrative gene expression database for inner ear research. Database 2015:1–9 Shen J, Scheffer DI, Kwan KY, Corey DP (2015) SHIELD: an integrative gene expression database for inner ear research. Database 2015:1–9
58.
go back to reference Agrawal Y, Carey JP, della Santina CC, Schubert MC, Minor LB. (2009) Disorders of balance and vestibular function in US adults: data from the National Health and Nutrition Examination Survey, 2001–2004. Arch Intern Med 169:938–944PubMed Agrawal Y, Carey JP, della Santina CC, Schubert MC, Minor LB. (2009) Disorders of balance and vestibular function in US adults: data from the National Health and Nutrition Examination Survey, 2001–2004. Arch Intern Med 169:938–944PubMed
59.
go back to reference Agrawal Y, van de Berg R, Wuyts F, Walther L, Magnusson M, Oh E, Sharpe M, Strupp M (2019) Presbyvestibulopathy: diagnostic criteria consensus document of the classification committee of the Bárány Society. J Vestib Res 29:161–170PubMedPubMedCentral Agrawal Y, van de Berg R, Wuyts F, Walther L, Magnusson M, Oh E, Sharpe M, Strupp M (2019) Presbyvestibulopathy: diagnostic criteria consensus document of the classification committee of the Bárány Society. J Vestib Res 29:161–170PubMedPubMedCentral
61.
go back to reference Sessoms PH, Gottshall KR, Sturdy J, Viirre E (2015) Head stabilization measurements as a potential evaluation tool for comparison of persons with TBI and vestibular dysfunction with healthy controls. Mil Med 180:135–142PubMed Sessoms PH, Gottshall KR, Sturdy J, Viirre E (2015) Head stabilization measurements as a potential evaluation tool for comparison of persons with TBI and vestibular dysfunction with healthy controls. Mil Med 180:135–142PubMed
62.
go back to reference Fu W, Zhao J, Hu W, Dai L, Jiang Z, Zhong S, Deng B, Huang Y, Wu W, Yin J (2021) LINC01224/ZNF91 promote stem cell-like properties and drive radioresistance in non-small cell lung cancer. Cancer Manag Res 13:5671–5681PubMedPubMedCentral Fu W, Zhao J, Hu W, Dai L, Jiang Z, Zhong S, Deng B, Huang Y, Wu W, Yin J (2021) LINC01224/ZNF91 promote stem cell-like properties and drive radioresistance in non-small cell lung cancer. Cancer Manag Res 13:5671–5681PubMedPubMedCentral
64.
66.
67.
go back to reference Stankiewicz P, Khan TN, Szafranski P, Slattery L, Streff H, Vetrini F, Bernstein JA, Brown CW, Rosenfeld JA, Rednam S, Scollon S, Bergstrom KL, Parsons DW, Plon SE, Vieira MW, Quaio CRDC, Baratela WAR, Acosta Guio JC, Armstrong R, Mehta SG, Rump P, Pfundt R, Lewandowski R, Fernandes EM, Shinde DN, Tang S, Hoyer J, Zweier C, Reis A, Bacino CA, Xiao R, Breman AM, Smith JL, Katsanis N, Bostwick B, Popp B, Davis EE, Yang Y (2017) Haploinsufficiency of the chromatin remodeler BPTF causes syndromic developmental and speech delay, postnatal microcephaly, and dysmorphic features. Am J Hum Genet 101:503–515PubMed Stankiewicz P, Khan TN, Szafranski P, Slattery L, Streff H, Vetrini F, Bernstein JA, Brown CW, Rosenfeld JA, Rednam S, Scollon S, Bergstrom KL, Parsons DW, Plon SE, Vieira MW, Quaio CRDC, Baratela WAR, Acosta Guio JC, Armstrong R, Mehta SG, Rump P, Pfundt R, Lewandowski R, Fernandes EM, Shinde DN, Tang S, Hoyer J, Zweier C, Reis A, Bacino CA, Xiao R, Breman AM, Smith JL, Katsanis N, Bostwick B, Popp B, Davis EE, Yang Y (2017) Haploinsufficiency of the chromatin remodeler BPTF causes syndromic developmental and speech delay, postnatal microcephaly, and dysmorphic features. Am J Hum Genet 101:503–515PubMed
68.
go back to reference Schmoker AM, Weinert JL, Markwood JM, Albretsen KS, Lunde ML, Weir ME, Ebert AM, Hinkle KL, Ballif BA (2020) FYN and ABL regulate the interaction networks of the DCBLD receptor family. Mol Cell Proteomics 19:1586–1601PubMedPubMedCentral Schmoker AM, Weinert JL, Markwood JM, Albretsen KS, Lunde ML, Weir ME, Ebert AM, Hinkle KL, Ballif BA (2020) FYN and ABL regulate the interaction networks of the DCBLD receptor family. Mol Cell Proteomics 19:1586–1601PubMedPubMedCentral
Metadata
Title
Genome-Wide Association Study of Chronic Dizziness in the Elderly Identifies Loci Implicating MLLT10, BPTF, LINC01224, and ROS1
Authors
Royce Clifford
Daniel Munro
Daniel Dochtermann
Poornima Devineni
Saiju Pyarajan
Francesca Telese
Abraham A. Palmer
Pejman Mohammadi
Rick Friedman
Million Veteran Program
Publication date
30-11-2023
Publisher
Springer US
Published in
Journal of the Association for Research in Otolaryngology / Issue 6/2023
Print ISSN: 1525-3961
Electronic ISSN: 1438-7573
DOI
https://doi.org/10.1007/s10162-023-00917-y

Other articles of this Issue 6/2023

Journal of the Association for Research in Otolaryngology 6/2023 Go to the issue