Biology subjects

Ioannidis, J.

Publications and source records attributed to Ioannidis, J..

18 recordsLinked to original sources

bioRxiv2026

Mapping scientific cosmopolitanism: scientists with publication records substantially split across multiple countries

We used Scopus data on 243949 top-cited scientists to map scientific cosmopolitanism defined as having at least two different countries that contribute alone at least 10 percent of an author published record as indexed in Scopus. 20.4 percent of the top-cited authors were cosmopolitan based on this definition. Based on current author affiliation, rates varied widely from 9% to 76% across countries with at least 250 top-cited authors. Countries with few top-cited authors had almost always high rates of cosmopolitanism. The proportion of top-cited authors who are cosmopolitan has steadily increased over time in younger generations among those who started publishing after 1965 reaching 43% recently. Large differences were also seen across scientific subfields from 1% in General Psychology and Cognitive Sciences to 46% in Econometrics. Across the 30 country pairs that were most over-represented, countries shared borders, languages, most common religion pairs, or any of these features in 15, 19, 26, and 29 cases, respectively. The map of cosmopolitan authors reveals a large and increasing proportion of the most influential scientists who share two or more scientific homes that each has made a substantial contribution to their career. Cosmopolitanism among scientists requires better study to help facilitate its potential positive contributions not only to individual scientists but to science and society more broadly.

scientific communication and education↗

bioRxiv2025

Science-wide mapping and ranking of institutions based on affiliated authors

Standardized information on the size of institutions and on their concentration of high-impact scientists is missing. Here, we generate institution-level data on 6,979 institutions with >=50 authors who have had >=15 Scopus-indexed items. We present data on the number and proportion of top-cited authors (according to a composite citation indicator) for each institution. The primary analysis considers 1,214,702 authors (145,704 top-cited in career-long impact) who started publishing in 1980 or later, have published >=40 Scopus-indexed items and >=5 single-, first- or last-authored items. There is modest overlap among top institutions based on volume and based on number of top-cited authors. However, there is minimal overlap when institutions with the highest proportions of top-cited authors are considered; these include mostly research institutes and tech organizations and a minority of universities. Institutions with few eligible authors have large uncertainty. We propose a percentile ranking of the 2,380 largest institutions that adjusts the number of top-cited authors for the proportion of those who have high (>95th percentile) self-citation rates and high rates of publications in Scopus-discontinued titles and further penalizes for authorships of retracted papers not due to publisher/journal errors. Institutions with the highest self-citation, discontinuation, and retraction penalties cluster in specific countries. Among countries with >=15 institutions among the 2,380, Saudi Arabia, China, Malaysia, Iran, India and Indonesia have the lowest median percentile rankings of their institutions (3.9th-21st percentile) due to high penalties. The publicly available datasets that we provide allow institution-level research assessments balancing high impact against retractions and gaming practices.

scientific communication and education↗

bioRxiv2025

Most science is published from countries lacking in democracy and freedom of press

BackgroundDemocracy and freedom of press may affect how science is prioritized, produced, communicated and disseminated. We aimed to map the production of scientific publications worldwide in terms of democracy and freedom of press ratings of countries. MethodsThis is a bibliometric study cross-linking global bibliometric data with democracy ratings and freedom of the press indices for countries around the world. Democracy ratings used the Democracy Index in 2024 and in 2006 (when first released by the Economist Intelligence Unit) and Freedom of Press ratings used the 2024 index by Reports Without Borders. The Scopus database was used for publications from each country. Fractional counts were assigned for publications co-authored by authors from different countries. Full articles, reviews, conference papers, books and book chapters were included. ResultsIn 2024, countries characterized as full democracies produced only 22% of the Scopus-indexed publications, versus 66% in 2006. There was no correlation between the ratio of publications indexed in 2024 versus 2006 and the absolute or relative change in Democracy Index between 2006 and 2024 (r=0.02 and r=0.00, respectively). 78% of publications in 2024 came from countries with problematic (including USA) or worse (including China) rating for freedom of press. Proportions of publications originated from countries with problematic or worse situations were 81%, 91%, 61%, 62%, and 63% for political, economic, legislative, sociocultural, and safety/security dimensions, respectively. Results were similar when limited to articles published in 2024 in journals with continuous annual presence in Scopus during 2006-2024. 87.1% of the highly cited papers published in 2024 (with 150 or more Scopus citations by November 23, 2025) have at least one author from a country that is not full democracy and 98.8% of these highly cited papers have at least one author from a country that does not have good freedom of press. ConclusionsMost published science originates from countries struggling or suffering in democracy and/or freedom of press. The deeper causes and implications of this emerging landscape require further study.

scientific communication and education↗

bioRxiv2025

Reporting quality, effect sizes, and biases for aging interventions: a methodological appraisal of the DrugAge database

Though interest has grown significantly over the past decades in interventions that may slow the aging process, most evidence for these interventions still comes from experiments in non-human animals. These studies may suffer from design, quality and reporting issues. The quality and reporting of preclinical studies have not yet been studied systematically in anti-aging research. Here we analyzed the DrugAge database, assessing reporting study quality, bias and effect sizes across 667 anti-aging preclinical studies. We found significant shortcomings in reporting of crucial design features such as randomization and blinding, as well as large variation in reporting quality and effects across species. Non-mammal findings typically did not translate to mammals. Although anti-aging interventions may have different effects depending on when they are started, most studies began giving the intervention under investigation very early in the organisms lifespan. Our findings suggest there is substantial room for improvement in preclinical anti-aging research.

physiology↗

bioRxiv2024

Features and signals in precocious citation impact: a meta-research study

Some scientists reach top citation impact in a very short time once they start publishing. The current analysis defined precocious citation impact as rising to become a top-cited scientist within t[≤]8 years after the first publication year. Ultra-precocious citation impact was defined similarly for t [≤]5 years. Top-cited authors included those in the top-2% of a previously validated composite citation indicator across 174 subfields of science or in the top-100,000 authors of that composite citation indicator across all science based on Scopus. Annual data between 2017 and 2023 show a strong increase over time, with 469 precocious and 66 ultra-precocious citation impact Scopus author IDs in 2023. In-depth assessment of validated ultra-precocious scientists in 2023, showed significantly higher frequency of less developed country affiliation (71%), clustering in 4 high-risk subfields (Environmental Sciences, Energy, Artificial Intelligence & Image Processing, Mechanical Engineering & Transports) (64%), self-citations for their field above the 95th percentile (31%), being top-cited only when self-citations were included (20%), citations to citing papers ratio for their field above the 95th percentile (15%), extreme publishing behavior (7%), and extreme citation orchestration metric c/h2<2.45 (15%) compared with all top-cited authors (p<0.005 for all signals). The 17 ultra-precocious citation impact authors in the 2017-2020 top-cited lists who had retractions by October 2024 showed on average 4 of these 7 signal indicators at the time they entered the top-cited list. While some authors with precocious citation impact may be stellar scientists, others probably herald massive manipulative or fraudulent behaviors infiltrating the scientific literature. Significance statementExtreme performance may herald either extreme excellence or extreme inappropriate and outright fraudulent practices. Some authors reach the very top ranks in cumulative citation impact within only a few years, while even accomplished scientists take decades to reach these levels, if ever. A science-wide analysis of the authors with the most impressively precocious citation performance reveals that most of them come from less developed countries with limited resources, they heavily cluster in some scientific subfields, and they often have multiple signal indicators that may suggest problematic behavior. Some of these scientists are unquestionably excellent, while others may be manipulative or fraudulent. Evaluation of extreme cases allows science-wide views of the penetration of massive manipulative practices in scientific publication and citation.

scientific communication and education↗

bioRxiv2024

A stable Netrin-1 fluorescent reporter chicken reveals cell-specific molecular signaturesduring optic fissure closure.

NTN1 is expressed in a wide range of developmental tissues and is essential for normal development. Here we describe the generation of a Netrin-1 reporter chicken line (NTN1-T2A-eGFP) by targeting green fluorescent protein into the NTN1 locus using CRISPR/Cas9 methodology. Our strategy gave 100% transmission of heterozygous (NTN1T2A-eGFP/+) embryos in which GFP localisation faithfully replicated endogenous NTN1 expression in the optic fissure and neural tube floorplate. Furthermore, all NTN1T2A-eGFP/+ embryos and hatched birds appeared phenotypically normal. We applied this resource to a pertinent developmental context - coloboma is a structural eye malformation characterised by failure of epithelial fusion during optic fissure closure (OFC) and NTN1 is specifically expressed in fusion pioneer cells at the edges of the optic fissure. We therefore optimised the isolation of GFP expressing cells from embryonic NTN1T2A-eGFP/+ eyes using spectral fluorescence cell-sorting and applied transcriptomic profiling of pioneer cells, which revealed multiple new OFC markers and novel pathways for developmental tissue fusion and coloboma. This work provides a novel fluorescent NTN1 chicken reporter line with broad experimental utility and is the first to directly molecularly characterise pioneer cells during OFC.

developmental biology↗

bioRxiv2024

Updated science-wide author databases of standardized citation indicators including retraction data

Citation metrics are widely used in research appraisal, but they provide incomplete views of scientists impact and research track record. Other indicators of research practices should be linked to citation data. We have updated a Scopus-based database of highly-cited scientists (top-2% in each scientific subfield according to a composite citation indicator) to incorporate retraction data. Using data from the Retraction Watch database (RWDB), retraction records were linked to Scopus citation data. Of 55,237 items in RWDB as of August 15, 2024, we excluded non-retractions, retractions clearly not due to any author error, retractions where the paper had been republished, and items not linkable to Scopus records. Eventually 39,468 eligible retractions were linked to Scopus. Among 217,097 top-cited scientists in career-long impact and 223,152 in single recent year (2023) impact, 7,083 (3.3%) and 8,747 (4.0%), respectively, had at least one retraction. Scientists with retracted publications had younger publication age, higher self-citation rates, and larger publication volume than those without any retracted publications. Retractions were more common in the life sciences and rare or nonexistent in several other disciplines. In several developing countries, very high proportions of top-cited scientists had retractions (highest in Senegal (66.7%), Ecuador (28.6%) and Pakistan (27.8%) in career-long citation impact lists). Variability in retraction rates across fields and countries suggests differences in research practices, scrutiny, and ease of retraction. Addition of retraction data enhances the granularity of top-cited scientists profiles, aiding in responsible research evaluation. However, caution is needed when interpreting retractions, as they do not always signify misconduct; further analysis on a case-by-case basis is essential. The database should hopefully provide a resource for meta-research and deeper insights into scientific practices.

scientific communication and education↗

bioRxiv2024

Leading researchers in the leadership of leading research universities: meta-research analysis

It is unknown to what extent leading researchers are currently involved in the leadership of leading research universities as presidents or as executive board members. The academic administrative leader (president or equivalent role) of each of the 146 Carnegie tier 1 USA universities and of any of the top-100 universities per Times Higher Education (THE) 2024 ranking and the members of the executive governing bodies (Board of Trustees, Council, Corporation or similar) for the each of the top-20 universities per THE 2024 ranking were examined for high citation impact in their scientific subfield. Highly-cited was defined as the top-2% of a composite citation indicator (that considers citations, h-index, co-authorship adjusted hm-index and citations to papers as single, first, last authors) in their main scientific subfield based on career-long impact until end-2022 among all scholars focusing in the same subfield and having published [≥]5 full papers. Very highly-cited was similarly defined as the top-0.2%. Science was divided into 174 fields per Science-Metrix classification. 38/146 (26%) tier 1 USA university leaders as of end-2023 were highly-cited and 5/146 (3%) were very highly-cited. The respective figures for the top-100 THE 2024 universities globally were 43/100 and 12/100. For the 13 US universities among the top-20 of THE 2024, the probability of their leader being highly-cited was lower (6/13, 46%) than the probability of a randomly chosen active full tenured professor from their faculty being highly-cited (52-77%). Across 444 board members of 14 top-10 THE 2024 universities with data, only 65 (15%) were academics, and 19 (4%) were highly-cited; academics were rare in USA university boards. Board members had predominantly careers in for-profit companies. In conclusion, leading research universities have a dearth of leaders who are high-impact researchers.

scientific communication and education↗

bioRxiv2024

When most fMRI connectivity cannot be detected: insights from time course reliability

The level of correlation between two phenomena is limited by the accuracy at which these phenomena are measured. Despite numerous group reliability studies, the strength of the fMRI connectivity correlation that can be detected given underlying within subject time course reliability remains elusive. Moreover, it is unclear how within subject time course reliability limits the robust detection of connectivity on the group level. We estimated connectivity from 50 individuals engaged in a working memory task. The grand mean connectivity of the connectome equaled r =0.41 (95% CI 0.31-0.50) for the test run and r =0.40 (95% CI 0.29-0.49) for the retest run. However, mean connectivity was reduced to r=0.09 (95% C.I. 0.03-0.16) when test-retest reliability and residual auto-correlations of single time courses were considered, suggesting that less than a quarter of the observed connectivity is reliably detectable. Null hypothesis significance testing (NHST)-based analysis revealed that within subject time course reliability markedly affects the significance levels at which paths can be detected at the group level. This was in particular the case when samples were small or connectome coordinates were randomly selected. With a sample of 50 individuals, the connectome of a test session was completely reproduced in retest sessions at P < 2.54e-6. Despite perfect group reproducibility at conservative p-values, on average only 0.81 percent of the observed connectivity could be attributed to working memory-related time course fluctuations after corrections. Time course reliability can offer valuable insights on the detectable connectivity and should be assessed more frequently in fMRI investigations.

neuroscience↗

bioRxiv2023

Evolving patterns of extremely productive publishing behavior across science

Extreme publishing behavior may reflect a combination of some authors with genuinely high publication output and of other people who have their names listed too frequently in publications because of consortium agreements, gift authorship or other spurious practices. We aimed to evaluate the evolution of extreme publishing behavior across countries and scientific fields during 2000-2022. Extreme publishing behavior was defined as having >60 full articles (original articles, reviews, conference papers) in a single calendar year and indexed in Scopus. We identified 3,191 authors with extreme publishing behavior across science excluding Physics and 12,624 such authors in Physics. While Physics had much higher numbers of extreme publishing authors in the past, in 2022 extreme publishing authors was almost as numerous in non-Physics and Physics disciplines (1,226 vs. 1,480). Excluding Physics, China had the largest number of extreme publishing authors, followed by the USA. The largest fold-wise increases between 2016 and 2022 (5-19-fold) occurred in Thailand, Saudi Arabia, Spain, India, Italy, Russia, Pakistan, and South Korea. Excluding Physics, most extreme publishing authors were in Clinical Medicine, but from 2016 to 2022 the largest relative increases (>6-fold) were seen in Agriculture, Fisheries & Forestry, Biology, and Mathematics and Statistics. Extreme publishing authors accounted for 4,360 of the 10,000 most-cited authors (based on raw citation count) across science. While most Physics authors with extreme publishing behavior had modest citation impact in a composite citation indicator that adjusts for co-authorship and author positions, 67% of authors with extreme publishing behavior in non-Physics fields remained within the top-2% according to that indicator among all authors with >=5 full articles. Extreme publishing behavior has become worryingly common across scientific fields with rapidly increasing rates in some countries and settings and may herald a rapid depreciation of authorship standards.

scientific communication and education↗

bioRxiv2023

Differential correction of gender imbalance for top-cited scientists across scientific subfields over time

We evaluated how the gender composition of top-cited authors within different subfields of research has evolved over time. We considered 9,071,122 authors with at least 5 full papers in Scopus as of September 1, 2022. Using a previously validated composite citation indicator, we identified the 2% top-cited authors for each of 174 science subfields (Science-Metrix classification) in 4 separate publication age cohorts (first publication pre-1992, 1992-2001, 2002-2011, post-2011). Using NamSor we assigned 3,784,507 authors as men, and 2,011,616 as women (for 36.1% gender assignment uncertain). Men outnumbered women 1.88-fold among all authors, decreasing from 3.93-fold to 1.36-fold over time. Men outnumbered women 3.21-fold among top-cited authors, decreasing from 6.41-fold to 2.28-fold over time. In the youngest (post-2011) cohort, 32/174 (18%) subfields had >=50% women, 97/174 (56%) subfields had >=30% women, and 3 subfields had =<10% women among the top-cited authors. Gender imbalances in author numbers decreased sharply over time in both high-income countries (including the USA) and other countries, but the latter had little improvement in gender imbalances for top-cited authors. In random samples of 100 women and 100 men from the youngest (post-2011) cohort, in-depth assessment showed that most were currently (April 2023) working in academic environments. 32 women and 44 men had some faculty appointment, but only 2 women and 2 men were full professors. Our analysis shows large heterogeneity across scientific disciplines in the amelioration of gender imbalances with more prominent imbalances persisting among top-cited authors and slow promotion pathways even for the most-cited young scientists.

scientific communication and education↗

bioRxiv2023

Paired associated SARS-CoV-2 spike variable positions: a network analysis approach to emerging variants

Amino acids in variable positions of proteins may be correlated, with potential structural and functional implications. Here, we apply exact tests of independence in R x C contingency tables to examine noise-free associations between variable positions of the SARS-CoV-2 spike protein, using as a paradigm sequences from Greece deposited in GISAID (N=6,683/1,078 full-length) for the period February 29, 2020 to April 26, 2021 that essentially covers the first three pandemic waves. We examine the fate and complexity of these associations by network analysis, using associated positions (exact p[≤]0.001 and Average Product Correction [≥]2) as links and the corresponding positions as nodes . We found a temporal linear increase of positional differences and a gradual expansion of the number of position associations over time, represented by a temporally evolving intricate web, resulting in a non-random complex network of 69 nodes and 252 links. Overconnected nodes corresponded to the most adapted variant positions in the population, suggesting a direct relation between network degree and position functional importance. Modular analysis revealed 25 k-cliques comprising three to 11 nodes. At different k- clique resolutions, one to four communities were formed, capturing epistatic associations of circulating variants (Alpha, Beta, B.1.1.318), but also Delta, which dominated the evolutionary landscape later in the pandemic. Cliques of aminoacidic positional associations tended to occur in single sequences, enabling the recognition of epistatic positions in real-world virus populations. Our findings provide a novel way of understanding epistatic relationships in viral proteins with potential applications in the design of virus control procedures. ImportancePaired positional associations of adapted amino acids in virus proteins may provide new insights for understanding virus evolution and variant formation. We investigated potential intramolecular relationships between variable SARS-CoV-2 spike positions by exact tests of independence in R x C contingency tables, having applied Average Product Correction (APC) to eliminate background noise. Associated positions (exact p[≤]0.001 and APC[≥]2) formed a non- random, epistatic network of 25 cliques and 1-4 communities at different clique resolutions, revealing evolutionary ties between variable positions of circulating variants, and a predictive potential of previously unknown network positions. Cliques of different sizes represented theoretical combinations of changing residues in sequence space, allowing the identification of significant aminoacidic combinations in single sequences of real-world populations. Our analytic approach that links network structural aspects to mutational aminoacidic combinations in the spike sequence population offers a novel way to understand virus epidemiology and evolution.

microbiology↗

bioRxiv2022

Prolific non-research authors in high impact scientific journals: meta-research study

Journalistic papers published in high impact journals can be very influential, especially in hot fields. This meta-research analysis aimed to evaluate the publication profiles, impact, and disclosures of conflicts of interest of non-research authors who had published >200 Scopus-indexed papers in Nature, Science, PNAS, Cell, BMJ, Lancet, JAMA or New England Journal of Medicine. 154 prolific authors were identified, 148 of whom had published 67,825 papers in their main affiliated journal in a non-researcher capacity. Of 25 massively prolific authors with over 700 publications in one of these journals, only 3 had a PhD degree in any subject matter. Only 2 of the 25 disclosed potential conflicts with some specificity. The practice of assigning so much power to non-researchers in shaping scientific discourse should be further debated and disclosures of potential conflicts of interest should be emphasized.

scientific communication and education↗

bioRxiv2022

Estrogen suppresses DMRT1 expression during ovarian development in the chicken

Primary sex determination is the choice between two different developmental fates, a testis or an ovary. This selection is thought to require the action of a master regulator gene that triggers expression of a gene cascade in the bipotential gonad precursor in one sex. The selection of a particular developmental pathway is also thought to suppress the alternative developmental pathway. In birds, where the male is the homogametic sex (ZZ) and females the heterogametic sex (ZW), the Z-linked transcription factor DMRT1 is considered the master regulator and has been shown to be essential for testis development, and to also inhibit the ovarian pathway. Here, we characterise in detail, DMRT1 transcription and protein levels during gonadal development in the chick. Our analysis suggests that DMRT1 protein levels are equivalent in male and female gonads during the bipotential phase of development, and that DMRT1 protein levels are reduced in the developing ovary during the differentiation phase. The reduction in DMRT1 protein levels in the somatic cells of the female medulla, coincides with the induction of aromatase expression and the initiation of estrogen synthesis. Analysis of sex-reversed gonads and mixed-sex chimeric gonads, suggests that the reduction in DMRT1 protein is due to inhibition of DMRT1 expression by estrogen. Our data suggests that estrogen signalling is involved in primary sex determination by regulation of DMRT1 protein expression.

developmental biology↗

bioRxiv2021

Comprehensive mapping of local and diaspora scientists: a database and analysis of 63951 Greek scientists

Research policy and planning for a given country may benefit from reliable data on both its scientific workforce as well as the diaspora of scientists for countries with substantial brain drain. Here we use a systematic approach using Scopus to generate a comprehensive country-level database of all scientists in Greece. Moreover, we expand that database to include also Greek diaspora scientists. The database that we have compiled includes 63951 scientists who have published at least 5 papers indexed in Scopus. Of those, 35116 have an affiliation in Greece. We validate the sensitivity and specificity of the database against different control sets of scientists. We also analyze the scientific disciplines of these scientists according to the Science Metrix classification (174 subfield disciplines) and provide detailed data on each of the 63951 scientists using multiple citation indicators and a composite thereof. These analyses demonstrate differential concentrations in specific subfields for the local versus the diaspora cohorts, as well as an advantage of the diaspora cohort in terms of citation indicators especially among top-impact researchers. The approach that we have taken can be applied to map also the scientific workforce of other countries and nations for evaluation, planning and policy purposes.

scientific communication and education↗

bioRxiv2020

The rapid, massive infection of the scientific literature and authors by COVID-19

We examined the extent to which the scientific workforce in different fields was engaged in publishing COVID-19-related papers. According to Scopus (data cut, August 1, 2021), 210,183 COVID-19-related publications included 720,801 unique authors, of which 360,005 authors had published at least 5 full papers in their career and 23,520 authors were at the top 2% of their scientific subfield based on a career-long composite citation indicator. The growth of COVID-19 authors was far more rapid and massive compared with cohorts of authors historically publishing on H1N1, Zika, Ebola, HIV/AIDS and tuberculosis. All 174 scientific subfields had some specialists who had published on COVID-19. In 109 of the 174 subfields of science, at least one in ten active, influential (top-2% composite citation indicator) authors in the subfield had authored something on COVID-19. 52 hyper-prolific authors had already at least 60 (and up to 227) COVID-19 publications each. Among the 300 authors with the highest composite citation indicator for their COVID-19 publications, most common countries were USA (n=67), China (n=52), UK (n=32), and Italy (n=18). The rapid and massive involvement of the scientific workforce in COVID-19-related work is unprecedented and creates opportunities and challenges. There is evidence for hyper-prolific productivity.

scientific communication and education↗

bioRxiv2020

Primary sex determination in chickens depends on DMRT1 dosage, but gonadal sex does not determine secondary sexual characteristics in adult birds

In birds, males are the homogametic sex (ZZ) and females the heterogametic sex (ZW), and primary sex determination is thought to depend on a sex chromosome gene dosage mechanism. Previous studies have suggested that the most likely sex-determinant is the Z chromosome gene DMRT1 (Doublesex and Mab-3 Related Transcription factor 1). To clarify this issue, we used a CRISPR-Cas9 based mono-allelic targeting approach and sterile surrogate hosts to generate birds with targeted mutations in the DMRT1 gene. The resulting chromosomally male (ZZ) chicken with a single functional copy of DMRT1 developed ovaries in place of testes, demonstrating the avian sex determining mechanism is based on DMRT1 dosage. These ZZ ovaries expressed typical female markers and showed clear evidence of follicular development. However, these ZZ adult birds with an ovary in place of testes were indistinguishable in appearance to wild type adult males, supporting the concept of cell-autonomous sex identity (CASI) in birds. In experiments where oestrogen synthesis was blocked in control ZW embryos, the resulting gonads developed as testes. In contrast, if oestrogen synthesis was blocked in ZW embryos that lacked DMRT1, the gonads invariably adopted an ovarian fate. Our analysis shows that DMRT1 is the key sex determination switch in birds and that it is essential for testis development, but that production of oestrogen is also a key factor in primary sex determination in chickens, and that this production is linked to DMRT1 expression.

developmental biology↗

bioRxiv2018

Systematic meta-analyses identify differentially expressed microRNAs in Parkinson’s disease

ObjectiveMicroRNA-mediated (dys)regulation of gene expression has been implicated in Parkinsons disease (PD), although results of microRNA expression studies remain inconclusive. We aimed to identify microRNAs that show consistent differential expression across all published expression studies in PD.\n\nMethodsWe performed a systematic literature search on microRNA expression studies in PD and extracted data from eligible publications. After stratification for brain, blood, and cerebrospinal fluid (CSF)-derived specimen we performed meta-analyses across microRNAs assessed in three or more independent datasets. Meta-analyses were performed using effect-size and p-value based methods, as applicable.\n\nResultsAfter screening 599 publications we identified 47 datasets eligible for meta-analysis. On these, we performed 160 meta-analyses on microRNAs quantified in brain (n=125), blood (n=31), or CSF samples (n=4). Twenty-one meta-analyses were performed using effect sizes. We identified 13 significantly (Bonferroni-adjusted =3.13x10-4) differentially expressed microRNAs in brain (n=3) and blood (n=10) with consistent effect directions across studies. The most compelling findings were with hsa-miR-132-3p (p=6.37x10-5), hsa-miR-497-5p (p=1.35x10-4), and hsa-miR-133b (p=1.90x10-4) in brain, and with hsa-miR-221-3p (p=4.49x10-35), hsa-miR-214-3p (p=2.00x10-34), and hsa-miR-29c-3p (p=3.00x10-12) in blood. No significant signals were found in CSF. Analyses of GWAS data for target genes of brain microRNAs showed significant association (=9.40x10-5) of genetic variants in nine loci.\n\nInterpretationWe identified several microRNAs that showed highly significant differential expression in PD. Future studies may assess the possible role of the identified brain miRNAs in pathogenesis and disease progression as well as the potential of the top blood microRNAs as biomarkers for diagnosis, progression or prediction of PD.

genetics↗