MyMedR

Displaying all 18 publications

Abstract:

Sort:

Fulltext Expert appraisal of criteria for assessing gaming disorder: an international Delphi study

Castro-Calvo J, King DL, Stein DJ, Brand M, Carmi L, Chamberlain SR, et al.

Addiction, 2021 09;116(9):2463-2475.
PMID: 33449441 DOI: 10.1111/add.15411

BACKGROUND AND AIMS: Following the recognition of 'internet gaming disorder' (IGD) as a condition requiring further study by the DSM-5, 'gaming disorder' (GD) was officially included as a diagnostic entity by the World Health Organization (WHO) in the 11th revision of the International Classification of Diseases (ICD-11). However, the proposed diagnostic criteria for gaming disorder remain the subject of debate, and there has been no systematic attempt to integrate the views of different groups of experts. To achieve a more systematic agreement on this new disorder, this study employed the Delphi expert consensus method to obtain expert agreement on the diagnostic validity, clinical utility and prognostic value of the DSM-5 criteria and ICD-11 clinical guidelines for GD.
METHODS: A total of 29 international experts with clinical and/or research experience in GD completed three iterative rounds of a Delphi survey. Experts rated proposed criteria in progressive rounds until a pre-determined level of agreement was achieved.
RESULTS: For DSM-5 IGD criteria, there was an agreement both that a subset had high diagnostic validity, clinical utility and prognostic value and that some (e.g. tolerance, deception) had low diagnostic validity, clinical utility and prognostic value. Crucially, some DSM-5 criteria (e.g. escapism/mood regulation, tolerance) were regarded as incapable of distinguishing between problematic and non-problematic gaming. In contrast, ICD-11 diagnostic guidelines for GD (except for the criterion relating to diminished non-gaming interests) were judged as presenting high diagnostic validity, clinical utility and prognostic value.
CONCLUSIONS: This Delphi survey provides a foundation for identifying the most diagnostically valid and clinically useful criteria for GD. There was expert agreement that some DSM-5 criteria were not clinically relevant and may pathologize non-problematic patterns of gaming, whereas ICD-11 diagnostic guidelines are likely to diagnose GD adequately and avoid pathologizing.
Hemodynamic response to exercise and head-up tilt of patients implanted with a rotary blood pump: a computational modeling study

Lim E, Salamonsen RF, Mansouri M, Gaddum N, Mason DG, Timms DL, et al.

Artif Organs, 2015 Feb;39(2):E24-35.
PMID: 25345482 DOI: 10.1111/aor.12370

The present study investigates the response of implantable rotary blood pump (IRBP)-assisted patients to exercise and head-up tilt (HUT), as well as the effect of alterations in the model parameter values on this response, using validated numerical models. Furthermore, we comparatively evaluate the performance of a number of previously proposed physiologically responsive controllers, including constant speed, constant flow pulsatility index (PI), constant average pressure difference between the aorta and the left atrium, constant average differential pump pressure, constant ratio between mean pump flow and pump flow pulsatility (ratioP I or linear Starling-like control), as well as constant left atrial pressure ( P l a ¯ ) control, with regard to their ability to increase cardiac output during exercise while maintaining circulatory stability upon HUT. Although native cardiac output increases automatically during exercise, increasing pump speed was able to further improve total cardiac output and reduce elevated filling pressures. At the same time, reduced venous return associated with upright posture was not shown to induce left ventricular (LV) suction. Although P l a ¯ control outperformed other control modes in its ability to increase cardiac output during exercise, it caused a fall in the mean arterial pressure upon HUT, which may cause postural hypotension or patient discomfort. To the contrary, maintaining constant average pressure difference between the aorta and the left atrium demonstrated superior performance in both exercise and HUT scenarios. Due to their strong dependence on the pump operating point, PI and ratioPI control performed poorly during exercise and HUT. Our simulation results also highlighted the importance of the baroreflex mechanism in determining the response of the IRBP-assisted patients to exercise and postural changes, where desensitized reflex response attenuated the percentage increase in cardiac output during exercise and substantially reduced the arterial pressure upon HUT.
A method for control of an implantable rotary blood pump for heart failure patients using noninvasive measurements

Lim E, Alomari AH, Savkin AV, Dokos S, Fraser JF, Timms DL, et al.

Artif Organs, 2011 Aug;35(8):E174-80.
PMID: 21843286 DOI: 10.1111/j.1525-1594.2011.01268.x

We propose a deadbeat controller for the control of pulsatile pump flow (Q(p) ) in an implantable rotary blood pump (IRBP). Noninvasive measurements of pump speed and current are used as inputs to a dynamical model of Q(p) estimation, previously developed and verified in our laboratory. The controller was tested using a lumped parameter model of the cardiovascular system (CVS), in combination with the stable dynamical models of Q(p) and differential pressure (head) estimation for the IRBP. The control algorithm was tested with both constant and sinusoidal reference Q(p) as input to the CVS model. Results showed that the controller was able to track the reference input with minimal error in the presence of model uncertainty. Furthermore, Q(p) was shown to settle to the desired reference value within a finite number of sampling periods. Our results also indicated that counterpulsation yields the minimum left ventricular stroke work, left ventricular end diastolic volume, and aortic pulse pressure, without significantly affecting mean cardiac output and aortic pressure.
Fulltext Culture and personal influences on cardiopulmonary resuscitation- results of international survey

Ozer J, Alon G, Leykin D, Varon J, Aharonson-Daniel L, Einav S

BMC Med Ethics, 2019 12 26;20(1):102.
PMID: 31878920 DOI: 10.1186/s12910-019-0439-x

BACKGROUND: The ethical principle of justice demands that resources be distributed equally and based on evidence. Guidelines regarding forgoing of CPR are unavailable and there is large variance in the reported rates of attempted CPR in in-hospital cardiac arrest. The main objective of this work was to study whether local culture and physician preferences may affect spur-of-the-moment decisions in unexpected in-hospital cardiac arrest.
METHODS: Cross sectional questionnaire survey conducted among a convenience sample of physicians that likely comprise code team members in their country (Indonesia, Israel and Mexico). The questionnaire included details regarding respondent demographics and training, personal value judgments and preferences as well as professional experience regarding CPR and forgoing of resuscitation.
RESULTS: Of the 675 questionnaires distributed, 617 (91.4%) were completed and returned. Country of practice and level of knowledge about resuscitation were strongly associated with avoiding CPR performance. Mexican physicians were almost twicemore likely to forgo CPR than their Israeli and Indonesian/Malaysian counterparts [OR1.84 (95% CI 1.03, 3.26), p = 0.038]. Mexican responders also placed greater emphasison personal and patient quality of life (p
Environmental and anthropogenic factors synergistically affect space use of jaguars

Thompson JJ, Morato RG, Niebuhr BB, Alegre VB, Oshima JEF, de Barros AE, et al.

Curr Biol, 2021 Aug 09;31(15):3457-3466.e4.
PMID: 34237270 DOI: 10.1016/j.cub.2021.06.029

Large terrestrial carnivores have undergone some of the largest population declines and range reductions of any species, which is of concern as they can have large effects on ecosystem dynamics and function.1-4 The jaguar (Panthera onca) is the apex predator throughout the majority of the Neotropics; however, its distribution has been reduced by >50% and it survives in increasingly isolated populations.5 Consequently, the range-wide management of the jaguar depends upon maintaining core populations connected through multi-national, transboundary cooperation, which requires understanding the movement ecology and space use of jaguars throughout their range.6-8 Using GPS telemetry data for 111 jaguars from 13 ecoregions within the four biomes that constitute the majority of jaguar habitat, we examined the landscape-level environmental and anthropogenic factors related to jaguar home range size and movement parameters. Home range size decreased with increasing net productivity and forest cover and increased with increasing road density. Speed decreased with increasing forest cover with no sexual differences, while males had more directional movements, but tortuosity in movements was not related to any landscape factors. We demonstrated a synergistic relationship between landscape-scale environmental and anthropogenic factors and jaguars' spatial needs, which has applications to the conservation strategy for the species throughout the Neotropics. Using large-scale collaboration, we overcame limitations from small sample sizes typical in large carnivore research to provide a mechanism to evaluate habitat quality for jaguars and an inferential modeling framework adaptable to the conservation of other large terrestrial carnivores.
A distinct Y-STR haplotype for Amelogenin negative males characterized by a large Y(p)11.2 (DYS458-MSY1-AMEL-Y) deletion

Chang YM, Perumal R, Keat PY, Yong RY, Kuehn DL, Burgoyne L

Forensic Sci Int, 2007 Mar 2;166(2-3):115-20.
PMID: 16765004

The use of STR multiplexes with the incorporated gender marker Amelogenin is common practice in forensic DNA analysis. However, when a known male sample shows a dropout of the Amelogenin Y-allele, the STR system falsely genotypes it as a female. To date, our laboratory has observed 18 such cases: 12 from our Y-STR database and six from casework. A study on 980 male individuals in the Malaysian population using the AmpFlSTR Y-filer has revealed a distinct Y-chromosome haplotype associated with the Amelogenin nulls. Our results showed that whilst the Amelogenin nulls were noticeably absent among the Chinese, both the Indians and Malays exhibited such mutations at 3.2 and 0.6%, respectively. It was also found that the Amelogenin negative individuals predominantly belonged to the J2e lineage, suggesting the possibility of a common ancestor for at least some of these chromosomes. The null frequencies showed concordance with the data published in Chang et al. [Higher failures of Amelogenin sex test in an Indian population group, J. Forensic Sci. 48 (2003) 1309-1313] on a smaller Malaysian population of 338 males which used a Y-STR triplex. In the current study, apart from the absence of the Amelogenin Y-locus, a complete absence of the DYS458 locus in all the nulls was also observed. This study together with the 2003 study has indicated a similar deletion region exists on the Y(p)11.2 band in all the 18 Y-chromosomes. Using bioinformatics, this deletion has been mapped to a region of at least 1.13 Mb on the Y(p)11.2 encompassing the Amelogenin, MSY1 minisatellite and DYS458 locus. Further, the Y-filer haplotypes revealed an additional null at Y-GATA H4 in two of the Indian males presented here.
Haplotype diversity of 16 Y-chromosomal STRs in three main ethnic populations (Malays, Chinese and Indians) in Malaysia

Chang YM, Perumal R, Keat PY, Kuehn DL

Forensic Sci Int, 2007 Mar 22;167(1):70-6.
PMID: 16457976

We have analyzed 16 Y-STR loci (DYS456, DYS389I, DYS390, DYS389II, DYS458, DYS19, DYS385a/b, DYS393, DYS391, DYS439, DYS635 or Y-GATA C4, DYS392, Y-GATA H4, DYS437, DYS438 and DYS448) from the non-recombining region of the human Y-chromosome in 980 male individuals from three main ethnic populations in Malaysia (Malay, Chinese, Indian) using the AmpFlSTR((R)) Y-filertrade mark (Applied Biosystems, Foster City, CA). The observed 17-loci haplotypes and the individual allele frequencies for each locus were estimated, whilst the locus diversity, haplotype diversity and discrimination capacity were calculated in the three ethnic populations. Analysis of molecular variance indicated that 88.7% of the haplotypic variation is found within population and 11.3% is between populations (fixation index F(ST)=0.113, p=0.000). This study has revealed Y-chromosomes with null alleles at several Y-loci, namely DYS458, DYS392, DYS389I, DYS389II, DYS439, DYS448 and Y-GATA H4; and several occurrences of duplications at the highly polymorphic DYS385 loci. Some of these deleted loci were in regions of the Y(q) arm that have been implicated in the occurrence of male infertility.
Editorial: Curcuminoids: their pleiotropism against hallmarks of cancers

Pouliquen DL, Gall Trošelj K, Anto RJ, Naidu R

Front Pharmacol, 2023;14:1266793.
PMID: 37675041 DOI: 10.3389/fphar.2023.1266793
Fulltext Key enablers and barriers of solar paver technologies for the advancement of environmental sustainability

Teh PL, Adebanjo D, Kong DLY

Heliyon, 2021 Oct;7(10):e08189.
PMID: 34729431 DOI: 10.1016/j.heliyon.2021.e08189

Global initiatives to improve environmental sustainability have centered on reducing energy consumption and developing technological solutions for greener power generation. Current insights on innovations for environmental sustainability are primarily from developed countries, with limited studies originating from developing countries. This study focuses on solar paver technology, a potential innovation for sustainable generation of power. The interest in this technology lies in its dual-purpose ability to enable both functional road surfaces and the use of solar roadways that can generate electricity to power other road infrastructure such as electric lights. To maximize the potential of success of deployment of solar pavers, it is important to investigate the practicalities of solar pavers and understand the perceptions of stakeholders that will be responsible for the implementation of solar pavers. This research addresses this gap in knowledge. Thirty construction industry stakeholders in Malaysia were interviewed through focus group discussions and interviews. This study applied the diffusion of innovation theory to develop an understanding of the nuances of solar pavers. The findings identified three superordinate categories (motivation, opportunity, and ability) and nine categories (compliance with green initiatives, promote corporate social responsibility, dual functionality, financial incentives, sunny climate, increased environmental awareness, green experience, experts network and familiarity with solar technology) as the key enablers. Key barriers constitute two superordinate categories (challenges and weaknesses) and ten categories (reluctant authority, vandalism, complexity of installation and maintenance, high humidity and rainfall, negative environmental impact, high cost, design flaws, low efficiency, questionable practicality, and better comparative opportunities). There is an acceptance of solar pavers by the stakeholders and cost and ownership structures are the key to the deployment. The findings provide fresh insights into a new form of sustainable solar paver engendering new streams of research in construction engineering and technology management. Implications for management and organizational research are discussed.
Fulltext Identification of pathways for bipolar disorder: a meta-analysis

Nurnberger JI, Koller DL, Jung J, Edenberg HJ, Foroud T, Guella I, et al.

JAMA Psychiatry, 2014 Jun;71(6):657-64.
PMID: 24718920 DOI: 10.1001/jamapsychiatry.2014.176

IMPORTANCE: Genome-wide investigations provide systematic information regarding the neurobiology of psychiatric disorders.
OBJECTIVE: To identify biological pathways that contribute to risk for bipolar disorder (BP) using genes with consistent evidence for association in multiple genome-wide association studies (GWAS).
DATA SOURCES: Four independent data sets with individual genome-wide data available in July 2011 along with all data sets contributed to the Psychiatric Genomics Consortium Bipolar Group by May 2012. A prior meta-analysis was used as a source for brain gene expression data.
STUDY SELECTION: The 4 published GWAS were included in the initial sample. All independent BP data sets providing genome-wide data in the Psychiatric Genomics Consortium were included as a replication sample.
DATA EXTRACTION AND SYNTHESIS: We identified 966 genes that contained 2 or more variants associated with BP at P
Fulltext Including gaming disorder in the ICD-11: The need to do so from a clinical and public health perspective

Rumpf HJ, Achab S, Billieux J, Bowden-Jones H, Carragher N, Demetrovics Z, et al.

J Behav Addict, 2018 09 01;7(3):556-561.
PMID: 30010410 DOI: 10.1556/2006.7.2018.59

The proposed introduction of gaming disorder (GD) in the 11th revision of the International Classification of Diseases (ICD-11) developed by the World Health Organization (WHO) has led to a lively debate over the past year. Besides the broad support for the decision in the academic press, a recent publication by van Rooij et al. (2018) repeated the criticism raised against the inclusion of GD in ICD-11 by Aarseth et al. (2017). We argue that this group of researchers fails to recognize the clinical and public health considerations, which support the WHO perspective. It is important to recognize a range of biases that may influence this debate; in particular, the gaming industry may wish to diminish its responsibility by claiming that GD is not a public health problem, a position which maybe supported by arguments from scholars based in media psychology, computer games research, communication science, and related disciplines. However, just as with any other disease or disorder in the ICD-11, the decision whether or not to include GD is based on clinical evidence and public health needs. Therefore, we reiterate our conclusion that including GD reflects the essence of the ICD and will facilitate treatment and prevention for those who need it.
Fulltext Gaming disorder: Its delineation as an important condition for diagnosis, management, and prevention

Saunders JB, Hao W, Long J, King DL, Mann K, Fauth-Bühler M, et al.

J Behav Addict, 2017 Sep 01;6(3):271-279.
PMID: 28816494 DOI: 10.1556/2006.6.2017.039

Online gaming has greatly increased in popularity in recent years, and with this has come a multiplicity of problems due to excessive involvement in gaming. Gaming disorder, both online and offline, has been defined for the first time in the draft of 11th revision of the International Classification of Diseases (ICD-11). National surveys have shown prevalence rates of gaming disorder/addiction of 10%-15% among young people in several Asian countries and of 1%-10% in their counterparts in some Western countries. Several diseases related to excessive gaming are now recognized, and clinics are being established to respond to individual, family, and community concerns, but many cases remain hidden. Gaming disorder shares many features with addictions due to psychoactive substances and with gambling disorder, and functional neuroimaging shows that similar areas of the brain are activated. Governments and health agencies worldwide are seeking for the effects of online gaming to be addressed, and for preventive approaches to be developed. Central to this effort is a need to delineate the nature of the problem, which is the purpose of the definitions in the draft of ICD-11.
Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials

Jones MN, Palmer KR, Pathirana MM, Cecatti JG, Filho OBM, Marions L, et al.

Lancet, 2022 Nov 12;400(10364):1681-1692.
PMID: 36366885 DOI: 10.1016/S0140-6736(22)01845-1

BACKGROUND: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods.
METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924).
FINDINGS: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%).
INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events.
FUNDING: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.
Fulltext Phylogenetic classification of the world's tropical forests

Slik JWF, Franklin J, Arroyo-Rodríguez V, Field R, Aguilar S, Aguirre N, et al.

Proc Natl Acad Sci U S A, 2018 02 20;115(8):1837-1842.
PMID: 29432167 DOI: 10.1073/pnas.1714977115

Knowledge about the biogeographic affinities of the world's tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world's tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
Fulltext An estimate of the number of tropical tree species

Slik JW, Arroyo-Rodríguez V, Aiba S, Alvarez-Loayza P, Alves LF, Ashton P, et al.

Proc Natl Acad Sci U S A, 2015 Jun 16;112(24):7472-7.
PMID: 26034279 DOI: 10.1073/pnas.1423147112

The high species richness of tropical forests has long been recognized, yet there remains substantial uncertainty regarding the actual number of tropical tree species. Using a pantropical tree inventory database from closed canopy forests, consisting of 657,630 trees belonging to 11,371 species, we use a fitted value of Fisher's alpha and an approximate pantropical stem total to estimate the minimum number of tropical forest tree species to fall between ∼ 40,000 and ∼ 53,000, i.e., at the high end of previous estimates. Contrary to common assumption, the Indo-Pacific region was found to be as species-rich as the Neotropics, with both regions having a minimum of ∼ 19,000-25,000 tree species. Continental Africa is relatively depauperate with a minimum of ∼ 4,500-6,000 tree species. Very few species are shared among the African, American, and the Indo-Pacific regions. We provide a methodological framework for estimating species richness in trees that may help refine species richness estimates of tree-dependent taxa.
Fulltext The Scales Project, a cross-national dataset on the interpretation of thermal perception scales

Schweiker M, Abdul-Zahra A, André M, Al-Atrash F, Al-Khatri H, Alprianti RR, et al.

Sci Data, 2019 11 26;6(1):289.
PMID: 31772199 DOI: 10.1038/s41597-019-0272-6

Thermal discomfort is one of the main triggers for occupants' interactions with components of the built environment such as adjustments of thermostats and/or opening windows and strongly related to the energy use in buildings. Understanding causes for thermal (dis-)comfort is crucial for design and operation of any type of building. The assessment of human thermal perception through rating scales, for example in post-occupancy studies, has been applied for several decades; however, long-existing assumptions related to these rating scales had been questioned by several researchers. The aim of this study was to gain deeper knowledge on contextual influences on the interpretation of thermal perception scales and their verbal anchors by survey participants. A questionnaire was designed and consequently applied in 21 language versions. These surveys were conducted in 57 cities in 30 countries resulting in a dataset containing responses from 8225 participants. The database offers potential for further analysis in the areas of building design and operation, psycho-physical relationships between human perception and the built environment, and linguistic analyses.
Fulltext Publisher Correction: The Scales Project, a cross-national dataset on the interpretation of thermal perception scales

Schweiker M, Abdul-Zahra A, André M, Al-Atrash F, Al-Khatri H, Alprianti RR, et al.

Sci Data, 2020 01 06;7(1):11.
PMID: 31907360 DOI: 10.1038/s41597-019-0348-3

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Fulltext Assessing the causal role of epigenetic clocks in the development of multiple cancers: a Mendelian randomization study

Morales Berstein F, McCartney DL, Lu AT, Tsilidis KK, Bouras E, Haycock P, et al.

Elife, 2022 Mar 29;11.
PMID: 35346416 DOI: 10.7554/eLife.75374

BACKGROUND: Epigenetic clocks have been associated with cancer risk in several observational studies. Nevertheless, it is unclear whether they play a causal role in cancer risk or if they act as a non-causal biomarker.
METHODS: We conducted a two-sample Mendelian randomization (MR) study to examine the genetically predicted effects of epigenetic age acceleration as measured by HannumAge (nine single-nucleotide polymorphisms (SNPs)), Horvath Intrinsic Age (24 SNPs), PhenoAge (11 SNPs), and GrimAge (4 SNPs) on multiple cancers (i.e. breast, prostate, colorectal, ovarian and lung cancer). We obtained genome-wide association data for biological ageing from a meta-analysis (N = 34,710), and for cancer from the UK Biobank (N cases = 2671-13,879; N controls = 173,493-372,016), FinnGen (N cases = 719-8401; N controls = 74,685-174,006) and several international cancer genetic consortia (N cases = 11,348-122,977; N controls = 15,861-105,974). Main analyses were performed using multiplicative random effects inverse variance weighted (IVW) MR. Individual study estimates were pooled using fixed effect meta-analysis. Sensitivity analyses included MR-Egger, weighted median, weighted mode and Causal Analysis using Summary Effect Estimates (CAUSE) methods, which are robust to some of the assumptions of the IVW approach.
RESULTS: Meta-analysed IVW MR findings suggested that higher GrimAge acceleration increased the risk of colorectal cancer (OR = 1.12 per year increase in GrimAge acceleration, 95% CI 1.04-1.20, p = 0.002). The direction of the genetically predicted effects was consistent across main and sensitivity MR analyses. Among subtypes, the genetically predicted effect of GrimAge acceleration was greater for colon cancer (IVW OR = 1.15, 95% CI 1.09-1.21, p = 0.006), than rectal cancer (IVW OR = 1.05, 95% CI 0.97-1.13, p = 0.24). Results were less consistent for associations between other epigenetic clocks and cancers.
CONCLUSIONS: GrimAge acceleration may increase the risk of colorectal cancer. Findings for other clocks and cancers were inconsistent. Further work is required to investigate the potential mechanisms underlying the results.
FUNDING: FMB was supported by a Wellcome Trust PhD studentship in Molecular, Genetic and Lifecourse Epidemiology (224982/Z/22/Z which is part of grant 218495/Z/19/Z). KKT was supported by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme) and by the Hellenic Republic's Operational Programme 'Competitiveness, Entrepreneurship & Innovation' (OΠΣ 5047228). PH was supported by Cancer Research UK (C18281/A29019). RMM was supported by the NIHR Biomedical Research Centre at University Hospitals Bristol and Weston NHS Foundation Trust and the University of Bristol and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). RMM is a National Institute for Health Research Senior Investigator (NIHR202411). The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. GDS and CLR were supported by the Medical Research Council (MC_UU_00011/1 and MC_UU_00011/5, respectively) and by a Cancer Research UK (C18281/A29019) programme grant (the Integrative Cancer Epidemiology Programme). REM was supported by an Alzheimer's Society project grant (AS-PG-19b-010) and NIH grant (U01 AG-18-018, PI: Steve Horvath). RCR is a de Pass Vice Chancellor's Research Fellow at the University of Bristol.

Filters

Please provide feedback to Administrator (afdal@afpm.org.my)

External Links