The UK Adult Twin Registry (TwinsUK)

2006 ◽  
Vol 9 (6) ◽  
pp. 899-906 ◽  
Author(s):  
Tim D. Spector ◽  
Frances M. K. Williams
Keyword(s):  
Aging Process ◽  
Association Studies ◽  
Media Campaigns ◽  
The United Kingdom ◽  
Twin Registry ◽  
Age Related ◽  
Genome Wide ◽  
The Uk ◽  
Intermediate Traits ◽  
Genome Wide Scan

AbstractThe UK Adult Twin Registry was started in 1993 and consists of approximately 10,000 monozygotic (MZ) and dizygotic (DZ) adult Caucasian twins aged 16 to 85 years from all over the United Kingdom, plus some parents and siblings. It now incorporates previous twin registries from the Institute of Psychiatry and Aberdeen University. This is a volunteer sample recruited by successive media campaigns without selecting for particular diseases or traits. All twins receive a series of detailed disease and environmental questionnaires. The majority of twins have been assessed in detail clinically at several time points for several hundred phenotypes related to common diseases or intermediate traits. The focus to date has been primarily in 5 areas — cardiovascular, metabolic, musculoskeletal, ophthalmologic diseases as well as the aging process. Over 3000 DZ twins have had a 10cM genome-wide scan performed and 5000 twins tagged for over 200 candidate genes allowing both linkage and association studies. The resource has led to many successful and innovative research projects particularly in common age-related diseases, and has led to collaborations with over 80 groups worldwide.

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.

scholarly journals Reproducibility in the UK Biobank of Genome-Wide Significant Signals Discovered in Earlier Genome-wide Association Studies

2020 ◽  
Author(s):  
Jack W. O’Sullivan ◽  
John P. A. Ioannidis
Keyword(s):  
Effect Size ◽  
Association Studies ◽  
Genome Wide Association ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Uk Biobank ◽  
Single Nucleotide ◽  
Genome Wide ◽  
The Uk ◽  
Open Question

AbstractWith the establishment of large biobanks, discovery of single nucleotide polymorphism (SNPs) that are associated with various phenotypes has been accelerated. An open question is whether SNPs identified with genome-wide significance in earlier genome-wide association studies (GWAS) are replicated also in later GWAS conducted in biobanks. To address this question, the authors examined a publicly available GWAS database and identified two, independent GWAS on the same phenotype (an earlier, “discovery” GWAS and a later, replication GWAS done in the UK biobank). The analysis evaluated 136,318,924 SNPs (of which 6,289 had reached p<5e-8 in the discovery GWAS) from 4,397,962 participants across nine phenotypes. The overall replication rate was 85.0% and it was lower for binary than for quantitative phenotypes (58.1% versus 94.8% respectively). There was a18.0% decrease in SNP effect size for binary phenotypes, but a 12.0% increase for quantitative phenotypes. Using the discovery SNP effect size, phenotype trait (binary or quantitative), and discovery p-value, we built and validated a model that predicted SNP replication with area under the Receiver Operator Curve = 0.90. While non-replication may often reflect lack of power rather than genuine false-positive findings, these results provide insights about which discovered associations are likely to be seen again across subsequent GWAS.

Age-related maculopathy: an expanded genome-wide scan with evidence of susceptibility loci within the 1q31 and 17q25 regions

2001 ◽  
Vol 132 (5) ◽  
pp. 682-692 ◽  
Author(s):  
Daniel E Weeks ◽  
Yvette P Conley ◽  
Hui-ju Tsai ◽  
Tammy S Mah ◽  
Philip J Rosenfeld ◽  
...  
Keyword(s):  
Susceptibility Loci ◽  
Age Related ◽  
Genome Wide ◽  
Genome Wide Scan

scholarly journals CONVERGENT AGING LOCI: PATHWAYS THAT TRANSCEND INDIVIDUAL DISEASES

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S221-S221
Author(s):  
Luke C Pilling ◽  
Luigi Ferrucci ◽  
David Melzer
Keyword(s):  
Disease Risk ◽  
Association Studies ◽  
Genome Wide Association Studies ◽  
Telomere Shortening ◽  
Chronic Disease Risk ◽  
Trade Offs ◽  
Age Related ◽  
Genome Wide ◽  
Artery Disease

Abstract Thousands of loci across the genome have been identified for specific diseases in genome-wide association studies (GWAS), yet very few are associated with lifespan itself. We hypothesized that specific biological pathways transcend individual diseases and affect health and lifespan more broadly. Using the published results for the most recent GWAS for 10 key age-related diseases (including coronary artery disease, type-2 diabetes, and several cancers) we identified 22 loci with a strong genetic association with at least three of the diseases. These multi-trait aging loci include known genes affecting multiple diverse health end points, such as CDKN2A/B (9p21.3) and APOE. There are also novel multi-trait genes including SH2B3 and CASC8, likely involved in hallmark pathways of aging biology, including telomere shortening and inflammation. Several of these loci involve trade-offs between chronic disease risk and cancer.

scholarly journals A Genome-Wide Scan Reveals Important Roles of DNA Methylation in Human Longevity by Regulating Age-Related Disease Genes

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120388 ◽  
Author(s):  
Fu-Hui Xiao ◽  
Yong-Han He ◽  
Qi-Gang Li ◽  
Huan Wu ◽  
Long-Hai Luo ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Human Longevity ◽  
Disease Genes ◽  
Related Disease ◽  
Age Related ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Scan

scholarly journals Novel genetic determinants of telomere length from a trans-ethnic analysis of 109,122 whole genome sequences in TOPMed

2019 ◽  
Author(s):  
Margaret A Taub ◽  
Matthew P Conomos ◽  
Rebecca Keener ◽  
Kruthika R Iyer ◽  
Joshua S Weinstock ◽  
...  
Keyword(s):  
Telomere Length ◽  
Association Studies ◽  
P Value ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Genetic Determinants ◽  
Age Related ◽  
Genome Wide ◽  
Variant Genotype ◽  
Effect Heterogeneity

ABSTRACTTelomeres shorten in replicating somatic cells, and telomere length (TL) is associated with age-related diseases 1,2. To date, 17 genome-wide association studies (GWAS) have identified 25 loci for leukocyte TL 3–19, but were limited to European and Asian ancestry individuals and relied on laboratory assays of TL. In this study from the NHLBI Trans-Omics for Precision Medicine (TOPMed) program, we used whole genome sequencing (WGS) of whole blood for variant genotype calling and the bioinformatic estimation of TL in n=109,122 trans-ethnic (European, African, Asian and Hispanic/Latino) individuals. We identified 59 sentinel variants (p-value <5×10−9) from 36 loci (20 novel, 13 replicated in external datasets). There was little evidence of effect heterogeneity across populations, and 10 loci had >1 independent signal. Fine-mapping at OBFC1 indicated the independent signals colocalized with cell-type specific eQTLs for OBFC1 (STN1). We further identified two novel genes, DCLRE1B (SNM1B) and PARN, using a multi-variant gene-based approach.

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