scholarly journals Genetics of age-related white matter lesions from linkage to genome wide association studies

2012 ◽  
Vol 322 (1-2) ◽  
pp. 82-86 ◽  
Author(s):  
Paul Freudenberger ◽  
Reinhold Schmidt ◽  
Helena Schmidt
Keyword(s):  
White Matter ◽  
Association Studies ◽  
White Matter Lesions ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Age Related ◽  
Genome Wide

scholarly journals Genome-wide association study of telomere length among South Asians identifies a second RTEL1 association signal

2017 ◽  
Vol 55 (1) ◽  
pp. 64-71 ◽  
Author(s):  
Dayana A Delgado ◽  
Chenan Zhang ◽  
Lin S Chen ◽  
Jianjun Gao ◽  
Shantanu Roy ◽  
...  
Keyword(s):  
Telomere Length ◽  
South Asian ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Genome Wide Association Studies ◽  
Age Related ◽  
Genome Wide ◽  
Potential Biomarker

BackgroundLeucocyte telomere length (TL) is a potential biomarker of ageing and risk for age-related disease. Leucocyte TL is heritable and shows substantial differences by race/ethnicity. Recent genome-wide association studies (GWAS) report ~10 loci harbouring SNPs associated with leucocyte TL, but these studies focus primarily on populations of European ancestry.ObjectiveThis study aims to enhance our understanding of genetic determinants of TL across populations.MethodsWe performed a GWAS of TL using data on 5075 Bangladeshi adults. We measured TL using one of two technologies (qPCR or a Luminex-based method) and used standardised variables as TL phenotypes.ResultsOur results replicate previously reported associations in the TERC and TERT regions (P=2.2×10−8 and P=6.4×10−6, respectively). We observed a novel association signal in the RTEL1 gene (intronic SNP rs2297439; P=2.82×10−7) that is independent of previously reported TL-associated SNPs in this region. The minor allele for rs2297439 is common in South Asian populations (≥0.25) but at lower frequencies in other populations (eg, 0.07 in Northern Europeans). Among the eight other previously reported association signals, all were directionally consistent with our study, but only rs8105767 (ZNF208) was nominally significant (P=0.003). SNP-based heritability estimates were as high as 44% when analysing close relatives but much lower when analysing distant relatives only.ConclusionsIn this first GWAS of TL in a South Asian population, we replicate some, but not all, of the loci reported in prior GWAS of individuals of European ancestry, and we identify a novel second association signal at the RTEL1 locus.

scholarly journals A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei Liu ◽  
Åsa Johansson ◽  
Helge Rask-Andersen ◽  
Mathias Rask-Andersen
Keyword(s):  
Hearing Loss ◽  
Association Studies ◽  
Molecular Study ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Confidence Set ◽  
Age Related ◽  
Genome Wide ◽  
The Uk ◽  
Age Related Hearing Loss

Abstract Background Sensorineural hearing loss is one of the most common sensory deficiencies. However, the molecular contribution to age-related hearing loss is not fully elucidated. Methods We performed genome-wide association studies (GWAS) for hearing loss-related traits in the UK Biobank (N = 362,396) and selected a high confidence set of ten hearing-associated gene products for staining in human cochlear samples: EYA4, LMX1A, PTK2/FAK, UBE3B, MMP2, SYNJ2, GRM5, TRIOBP, LMO-7, and NOX4. Results All proteins were found to be expressed in human cochlear structures. Our findings illustrate cochlear structures that mediate mechano-electric transduction of auditory stimuli, neuronal conductance, and neuronal plasticity to be involved in age-related hearing loss. Conclusions Our results suggest common genetic variation to influence structural resilience to damage as well as cochlear recovery after trauma, which protect against accumulated damage to cochlear structures and the development of hearing loss over time.

scholarly journals Genome-wide association study identifies 44 independent genomic loci for self-reported adult hearing difficulty in the UK Biobank cohort

2019 ◽  
Author(s):  
Helena RR. Wells ◽  
Maxim B. Freidin ◽  
Fatin N. Zainul Abidin ◽  
Antony Payton ◽  
Piers Dawes ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Genome Wide Association Study ◽  
Association Studies ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Age Related ◽  
Genome Wide ◽  
Hearing Difficulty ◽  
The Uk

Age-related hearing impairment (ARHI) is the most common sensory impairment in the aging population; a third of individuals are affected by disabling hearing loss by the age of 651. ARHI is a multifactorial condition caused by both genetic and environmental factors, with estimates of heritability between 35% and 55%2–4. The genetic risk factors and underlying biological pathology of ARHI are largely unknown, meaning that targets for new therapies remain elusive. We performed genome-wide association studies (GWAS) for two self-reported hearing phenotypes, hearing difficulty (HDiff) and hearing aid use (HAid), using over 250,000 UK Biobank5 volunteers aged between 40-69 years. We identified 44 independent genome-wide significant loci (P<5E-08), 33 of which have not previously been associated with any form of hearing loss. Gene sets from these loci are enriched in auditory processes such as synaptic activities, nervous system processes, inner ear morphology and cognition. Immunohistochemistry for protein localisation in adult mouse cochlea indicate metabolic, sensory and neuronal functions for NID2, CLRN2 and ARHGEF28 identified in the GWAS. These results provide new insight into the genetic landscape underlying susceptibility to ARHI.

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