Genome-wide association study of the common retinal disorder epiretinal membrane: Significant risk loci in each of three American populations.

Epiretinal membrane (ERM) is a common retinal condition characterized by the presence of fibrocellular tissue on the retinal surface, often with visual distortion and loss of visual acuity. We studied European American (EUR), African American (AFR), and Latino (admixed American, AMR) ERM participants in the Million Veteran Program (MVP) for genome-wide association analysis-a total of 38,232 case individuals and 557,988 control individuals. We completed a genome-wide association study (GWAS) in each population separately, and then results were meta-analyzed. Genome-wide significant (GWS) associations were observed in all three populations studied: 31 risk loci in EUR subjects, 3 in AFR, and 2 in AMR, with 48 in trans-ancestry meta-analysis. Many results replicated in the FinnGen sample. Several GWS variants associate to alterations in gene expression in the macula. ERM showed significant genetic correlation to multiple traits. Pathway enrichment analyses implicated collagen and collagen-adjacent mechanisms, among others. This well-powered ERM GWAS identified novel genetic associations that point to biological mechanisms for ERM.

Genome-wide association study identifies 30 obsessive-compulsive disorder associated loci.

Obsessive-compulsive disorder (OCD) affects ~1% of the population and exhibits a high SNP-heritability, yet previous genome-wide association studies (GWAS) have provided limited information on the genetic etiology and underlying biological mechanisms of the disorder. We conducted a GWAS meta-analysis combining 53,660 OCD cases and 2,044,417 controls from 28 European-ancestry cohorts revealing 30 independent genome-wide significant SNPs and a SNP-based heritability of 6.7%. Separate GWAS for clinical, biobank, comorbid, and self-report sub-groups found no evidence of sample ascertainment impacting our results. Functional and positional QTL gene-based approaches identified 249 significant candidate risk genes for OCD, of which 25 were identified as putatively causal, highlighting WDR6, DALRD3, CTNND1 and genes in the MHC region. Tissue and single-cell enrichment analyses highlighted hippocampal and cortical excitatory neurons, along with D1- and D2-type dopamine receptor-containing medium spiny neurons, as playing a role in OCD risk. OCD displayed significant genetic correlations with 65 out of 112 examined phenotypes. Notably, it showed positive genetic correlations with all included psychiatric phenotypes, in particular anxiety, depression, anorexia nervosa, and Tourette syndrome, and negative correlations with a subset of the included autoimmune disorders, educational attainment, and body mass index.. This study marks a significant step toward unraveling its genetic landscape and advances understanding of OCD genetics, providing a foundation for future interventions to address this debilitating disorder.

Genetic influences and causal pathways shared between cannabis use disorder and other substance use traits.

Cannabis use disorder (CanUD) has increased with the legalization of the use of cannabis. Around 20% of individuals using cannabis develop CanUD, and the number of users has grown with increasing ease of access. CanUD and other substance use disorders (SUDs) are associated phenotypically and genetically. We leveraged new CanUD genomics data to undertake genetically-informed analyses with unprecedented power, to investigate the genetic architecture and causal relationships between CanUD and lifetime cannabis use with risk for developing SUDs and substance use traits. Analyses included calculating local and global genetic correlations, genomic structural equation modeling (genomicSEM), and Mendelian Randomization (MR). Results from the genetic correlation and genomicSEM analyses demonstrated that CanUD and cannabis use differ in their relationships with SUDs and substance use traits. We found significant causal effects of CanUD influencing all the analyzed traits: opioid use disorder (OUD) (Inverse variant weighted, IVW ß = 0.925 ± 0.082), problematic alcohol use (PAU) (IVW ß = 0.443 ± 0.030), drinks per week (DPW) (IVW ß = 0.182 ± 0.025), Fagerström Test for Nicotine Dependence (FTND) (IVW ß = 0.183 ± 0.052), cigarettes per day (IVW ß = 0.150 ± 0.045), current versus former smokers (IVW ß = 0.178 ± 0.052), and smoking initiation (IVW ß = 0.405 ± 0.042). We also found evidence of bidirectionality showing that OUD, PAU, smoking initiation, smoking cessation, and DPW all increase risk of developing CanUD. For cannabis use, bidirectional relationships were inferred with PAU, smoking initiation, and DPW; cannabis use was also associated with a higher risk of developing OUD (IVW ß = 0.785 ± 0.266). GenomicSEM confirmed that CanUD and cannabis use load onto different genetic factors. We conclude that CanUD and cannabis use can increase the risk of developing other SUDs. This has substantial public health implications; the move towards legalization of cannabis use may be expected to increase other kinds of problematic substance use. These harmful outcomes are in addition to the medical harms associated directly with CanUD.

Automated control and stabilization of ultrabroadband laser pulse angular dispersion.

We present an innovative automatic control of angular dispersion for high-power laser systems. A novel, to the best of our knowledge, diagnostic has been developed to visualize angular dispersion in ultrashort near-infrared laser pulses for on-shot analysis. The output of a commercial ultrabroadband oscillator was prepared with an arbitrary chromatic dispersion and sent through a compensation system composed of 4° glass wedges in motorized mounts. These wedges were rotationally controlled in discrete steps about the beam axis in accordance with the diagnostic, via an automated feedback loop, to successfully eliminate angular dispersion to a precision of 5 nrad/nm. The system can be implemented to maintain a zero or nonzero target dispersion for experiments.

A genome-wide investigation into the underlying genetic architecture of personality traits and overlap with psychopathology.

Personality is influenced by both genetic and environmental factors and is associated with other psychiatric traits such as anxiety and depression. The "Big Five" personality traits, which include neuroticism, extraversion, agreeableness, conscientiousness, and openness, are a widely accepted and influential framework for understanding and describing human personality. Of the big five personality traits, neuroticism has most often been the focus of genetic studies and is linked to various mental illnesses including depression, anxiety, and schizophrenia. Our knowledge of the genetic architecture of the other four personality traits is more limited. Utilizing the Million Veteran Program (MVP) cohort we conducted a genome-wide association study (GWAS) in individuals of European and African ancestry. Adding other published data, we performed GWAS meta-analysis for each of the five personality traits with sample sizes ranging from 237,390 to 682,688. We identified 158, 14, 3, 2, and 7 independent genome-wide significant (GWS) loci associated with neuroticism, extraversion, agreeableness, conscientiousness, and openness, respectively. These findings represent 55 novel loci for neuroticism, as well as the first GWS loci discovered for extraversion and agreeableness. Gene-based association testing revealed 254 genes showing significant association with at least one of the five personality traits. Transcriptome-wide and proteome-wide analysis identified altered expression of genes and proteins such as CRHR1, SLC12A5, MAPT, and STX4. Pathway enrichment and drug perturbation analyses identified complex biology underlying human personality traits. We also studied the inter-relationship of personality traits with 1,437 other traits in a phenome-wide genetic correlation analysis, identifying new associations. Mendelian randomization showed positive bidirectional effects between neuroticism and depression and anxiety while a negative bidirectional effect was observed for agreeableness and these psychiatric traits. This study improves our comprehensive understanding of the genetic architecture underlying personality traits and their relationship to other complex human traits.

Multi-ancestry study of the genetics of problematic alcohol use in over 1 million individuals.

Problematic alcohol use (PAU), a trait that combines alcohol use disorder and alcohol-related problems assessed with a questionnaire, is a leading cause of death and morbidity worldwide. Here we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals (European, N = 903,147; African, N = 122,571; Latin American, N = 38,962; East Asian, N = 13,551; and South Asian, N = 1,716 ancestries). We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by a computational drug repurposing analysis. Cross-ancestry polygenic risk scores showed better performance of association in independent samples than single-ancestry polygenic risk scores. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. This study advances our knowledge of the genetic etiology of PAU, and these findings may bring possible clinical applicability of genetics insights-together with neuroscience, biology and data science-closer.

Multi-ancestry genome-wide association study of cannabis use disorder yields insight into disease biology and public health implications.

As recreational use of cannabis is being decriminalized in many places and medical use widely sanctioned, there are growing concerns about increases in cannabis use disorder (CanUD), which is associated with numerous medical comorbidities. Here we performed a genome-wide association study of CanUD in the Million Veteran Program (MVP), followed by meta-analysis in 1,054,365 individuals (ncases = 64,314) from four broad ancestries designated by the reference panel used for assignment (European n = 886,025, African n = 123,208, admixed American n = 38,289 and East Asian n = 6,843). Population-specific methods were applied to calculate single nucleotide polymorphism-based heritability within each ancestry. Statistically significant single nucleotide polymorphism-based heritability for CanUD was observed in all but the smallest population (East Asian). We discovered genome-wide significant loci unique to each ancestry: 22 in European, 2 each in African and East Asian, and 1 in admixed American ancestries. A genetically informed causal relationship analysis indicated a possible effect of genetic liability for CanUD on lung cancer risk, suggesting potential unanticipated future medical and psychiatric public health consequences that require further study to disentangle from other known risk factors such as cigarette smoking.

Genome-wide association studies and cross-population meta-analyses investigating short and long sleep duration.

Sleep duration has been linked to a wide range of negative health outcomes and to reduced life expectancy. We present genome-wide association studies of short ( ≤ 5 h) and long ( ≥ 10 h) sleep duration in adults of European (N = 445,966), African (N = 27,785), East Asian (N = 3141), and admixed-American (N = 16,250) ancestry from UK Biobank and the Million Veteran Programme. In a cross-population meta-analysis, we identify 84 independent loci for short sleep and 1 for long sleep. We estimate SNP-based heritability for both sleep traits in each ancestry based on population derived linkage disequilibrium (LD) scores using cov-LDSC. We identify positive genetic correlation between short and long sleep traits (rg = 0.16 ± 0.04; p = 0.0002), as well as similar patterns of genetic correlation with other psychiatric and cardiometabolic phenotypes. Mendelian randomisation reveals a directional causal relationship between short sleep and depression, and a bidirectional causal relationship between long sleep and depression.

Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals.

Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature.

Genome-Wide Investigation of Maximum Habitual Alcohol Intake in US Veterans in Relation to Alcohol Consumption Traits and Alcohol Use Disorder.

Importance: Alcohol genome-wide association studies (GWASs) have generally focused on alcohol consumption and alcohol use disorder (AUD); few have examined habitual drinking behaviors like maximum habitual alcohol intake (MaxAlc). Objectives: To identify genetic loci associated with MaxAlc and to elucidate the genetic architecture across alcohol traits. Design, Setting, and Participants: This MaxAlc genetic association study was performed among Million Veteran Program participants enrolled from January 10, 2011, to September 30, 2020. Ancestry-specific GWASs were conducted in participants with European (n = 218 623) and African (n = 29 132) ancestry, then meta-analyzed (N = 247 755). Linkage-disequilibrium score regression was used to estimate single nucleotide variant (SNV)-heritability and genetic correlations (rg) with other alcohol and psychiatric traits. Genomic structural equation modeling (gSEM) was used to evaluate genetic associations between MaxAlc and other alcohol traits. Mendelian randomization was used to examine potential causal relationships between MaxAlc and liver enzyme levels. MTAG (multitrait analysis of GWAS) was used to analyze MaxAlc and problematic alcohol use (PAU) jointly. Exposures: Genetic associations. Main Outcomes and Measures: MaxAlc was defined from the following survey item: "in a typical month, what is/was the largest number of drinks of alcohol you may have had in one day?" with ordinal responses from 0 to 15 or more drinks. Results: GWASs were conducted on sample sizes of as many as 247 455 US veterans. Participants were 92.68% male and had mean (SD) age of 65.92 (11.70) years. The MaxAlc GWAS resulted in 15 genome-wide significant loci. Top associations in European-ancestry and African-ancestry participants were with known functional variants in the ADH1B gene, namely rs1229984 (P = 3.12 × 10-101) and rs2066702 (P = 6.30 × 10-17), respectively. Novel associations were also found. SNV-heritability was 6.65% (SE, 0.41) in European-ancestry participants and 3.42% (SE, 1.46) in African-ancestry participants. MaxAlc was positively correlated with PAU (rg = 0.79; P = 3.95 × 10-149) and AUD (rg = 0.76; P = 1.26 × 10-127) and had negative rg with the UK Biobank "alcohol usually taken with meals" (rg = -0.53; P = 1.40 × 10-50). For psychiatric traits, MaxAlc had the strongest genetic correlation with suicide attempt (rg = 0.40; P = 3.02 × 10-21). gSEM supported a 2-factor model with MaxAlc loading on a factor with PAU and AUD and other alcohol consumption measures loading on a separate factor. Mendelian randomization supported an association between MaxAlc and the liver enzyme gamma-glutamyltransferase (ß = 0.012; P = 2.66 × 10-10). MaxAlc MTAG resulted in 31 genome-wide significant loci. Conclusions and Relevance: The findings suggest that MaxAlc closely aligns genetically with PAU traits. This study improves understanding of the mechanisms associated with normative alcohol consumption vs problematic habitual use and AUD as well as how MaxAlc relates to psychiatric and medical conditions genetically and biologically.

Genome-wide association study in individuals of European and African ancestry and multi-trait analysis of opioid use disorder identifies 19 independent genome-wide significant risk loci.

Despite the large toll of opioid use disorder (OUD), genome-wide association studies (GWAS) of OUD to date have yielded few susceptibility loci. We performed a large-scale GWAS of OUD in individuals of European (EUR) and African (AFR) ancestry, optimizing genetic informativeness by performing MTAG (Multi-trait analysis of GWAS) with genetically correlated substance use disorders (SUDs). Meta-analysis included seven cohorts: the Million Veteran Program, Psychiatric Genomics Consortium, iPSYCH, FinnGen, Partners Biobank, BioVU, and Yale-Penn 3, resulting in a total N = 639,063 (Ncases = 20,686;Neffective = 77,026) across ancestries. OUD cases were defined as having a lifetime OUD diagnosis, and controls as anyone not known to meet OUD criteria. We estimated SNP-heritability (h2SNP) and genetic correlations (rg). Based on genetic correlation, we performed MTAG on OUD, alcohol use disorder (AUD), and cannabis use disorder (CanUD). A leave-one-out polygenic risk score (PRS) analysis was performed to compare OUD and OUD-MTAG PRS as predictors of OUD case status in Yale-Penn 3. The EUR meta-analysis identified three genome-wide significant (GWS; p ≤ 5 × 10-8) lead SNPs-one at FURIN (rs11372849; p = 9.54 × 10-10) and two OPRM1 variants (rs1799971, p = 4.92 × 10-09; rs79704991, p = 1.11 × 10-08; r2 = 0.02). Rs1799971 (p = 4.91 × 10-08) and another OPRM1 variant (rs9478500; p = 1.95 × 10-08; r2 = 0.03) were identified in the cross-ancestry meta-analysis. Estimated h2SNP was 12.75%, with strong rg with CanUD (rg = 0.82; p = 1.14 × 10-47) and AUD (rg = 0.77; p = 6.36 × 10-78). The OUD-MTAG resulted in a GWAS Nequivalent = 128,748 and 18 independent GWS loci, some mapping to genes or gene regions that have previously been associated with psychiatric or addiction phenotypes. The OUD-MTAG PRS accounted for 3.81% of OUD variance (beta = 0.61;s.e. = 0.066; p = 2.00 × 10-16) compared to 2.41% (beta = 0.45; s.e. = 0.058; p = 2.90 × 10-13) explained by the OUD PRS. The current study identified OUD variant associations at OPRM1, single variant associations with FURIN, and 18 GWS associations in the OUD-MTAG. The genetic architecture of OUD is likely influenced by both OUD-specific loci and loci shared across SUDs.

Selection on ancestral genetic variation fuels repeated ecotype formation in bottlenose dolphins.

Studying repeated adaptation can provide insights into the mechanisms allowing species to adapt to novel environments. Here, we investigate repeated evolution driven by habitat specialization in the common bottlenose dolphin. Parapatric pelagic and coastal ecotypes of common bottlenose dolphins have repeatedly formed across the oceans. Analyzing whole genomes of 57 individuals, we find that ecotype evolution involved a complex reticulated evolutionary history. We find parallel linked selection acted upon ancient alleles in geographically distant coastal populations, which were present as standing genetic variation in the pelagic populations. Candidate loci evolving under parallel linked selection were found in ancient tracts, suggesting recurrent bouts of selection through time. Therefore, despite the constraints of small effective population size and long generation time on the efficacy of selection, repeated adaptation in long-lived social species can be driven by a combination of ecological opportunities and selection acting on ancestral standing genetic variation.

Ancestry may confound genetic machine learning: Candidate-gene prediction of opioid use disorder as an example.

BACKGROUND: Machine learning (ML) models are beginning to proliferate in psychiatry, however machine learning models in psychiatric genetics have not always accounted for ancestry. Using an empirical example of a proposed genetic test for OUD, and exploring a similar test for tobacco dependence and a simulated binary phenotype, we show that genetic prediction using ML is vulnerable to ancestral confounding. METHODS: We utilize five ML algorithms trained with 16 brain reward-derived "candidate" SNPs proposed for commercial use and examine their ability to predict OUD vs. ancestry in an out-of-sample test set (N = 1000, stratified into equal groups of n = 250 cases and controls each of European and African ancestry). We rerun analyses with 8 random sets of allele-frequency matched SNPs. We contrast findings with 11 genome-wide significant variants for tobacco smoking. To document generalizability, we generate and test a random phenotype. RESULTS: None of the 5 ML algorithms predict OUD better than chance when ancestry was balanced but were confounded with ancestry in an out-of-sample test. In addition, the algorithms preferentially predicted admixed subpopulations. Random sets of variants matched to the candidate SNPs by allele frequency produced similar bias. Genome-wide significant tobacco smoking variants were also confounded by ancestry. Finally, random SNPs predicting a random simulated phenotype show that the bias attributable to ancestral confounding could impact any ML-based genetic prediction. CONCLUSIONS: Researchers and clinicians are encouraged to be skeptical of claims of high prediction accuracy from ML-derived genetic algorithms for polygenic traits like addiction, particularly when using candidate variants.

Economic Impact of COVID-19 Lockdown on Italian NHS: Focus on Diabetes Mellitus.

BACKGROUND: In Italy, the adoption of a total lockdown has generated almost total suspension of outpatient visits except for emergencies. Even after lockdown, the pandemic fear created additional barriers to access the health services. The aim of our study is to evaluate the economic impact of the lockdown for COVID-19 on public health in Italy, focusing on its effects on diabetic population. MATERIALS AND METHODS: We analyzed the impact of the lockdown on excess mortality and morbidity in the Italian diabetic population during 2020. The analysis was divided into several steps: a quantification of specialist visit reduction, the calculation of excess mortality in the diabetic population, the economic evaluation of the slowdown in the use of innovative diabetic therapies. Furthermore, the impact of the lockdown on the reduction of procedures and follow-up visits in diabetic population was evaluated. The overall impact of the pandemic and lockdown effects on costs and quality of life was then calculated. RESULTS: During 2020, a drop of 28% in patient access has been observed. Diabetic patients recorded a twice higher mortality value compared to general population (20.4% vs 10.2%). The analysis of market data revealed a slowdown in consumption of new antidiabetic therapies (-14%, 27% vs 41%). We estimated an expense of €26.6 million for NHS and a loss of 257 utilities in diabetic population due to the missed benefits related to slowdown in innovative antidiabetic drugs use and non-optimal follow-up and control of diabetes complications. In simulation scenarios, we also estimated an overall expenditure ranging from €38.7 to 94.0 million and a loss of 294-836 utilities. CONCLUSION: Diabetic population paid a high tribute to pandemic and lockdown, both in terms of number of deaths and burden of diabetic complications, together with an overall deterioration of quality of life.

Detecting Selection from Linked Sites Using an F-Model.

Allele frequencies vary across populations and loci, even in the presence of migration. While most differences may be due to genetic drift, divergent selection will further increase differentiation at some loci. Identifying those is key in studying local adaptation, but remains statistically challenging. A particularly elegant way to describe allele frequency differences among populations connected by migration is the F-model, which measures differences in allele frequencies by population specific FST coefficients. This model readily accounts for multiple evolutionary forces by partitioning FST coefficients into locus- and population-specific components reflecting selection and drift, respectively. Here we present an extension of this model to linked loci by means of a hidden Markov model (HMM), which characterizes the effect of selection on linked markers through correlations in the locus specific component along the genome. Using extensive simulations, we show that the statistical power of our method is up to twofold higher than that of previous implementations that assume sites to be independent. We finally evidence selection in the human genome by applying our method to data from the Human Genome Diversity Project (HGDP).

Pulse front tilt control using non-collimated beams in a single pass grating compressor.

High power laser systems based on the chirped pulse amplification (CPA) technique make use of grating pairs to compress the pulse to a short duration. When designing the pulse compressor, it is normally assumed that good beam collimation is a strong requirement in order to avoid spatio-temporal couplings. We analyze the propagation through a single pass compressor without the good collimation approximation and show that this results in a compressed pulse exhibiting pulse front tilt, whose magnitude is proportional to the normalized distance to the beam waist, providing a simple mechanism for controlling the tilt angle. We perform experimental measurements in a large-scale CPA laser for a range of beam curvatures that confirm these results.

Control of temporal shape of nanosecond long lasers using feedback loops.

We present developments in the control of the temporal pulse shape of nanosecond lasers. An active feedback loop between a regenerative amplified laser's output and input was controlled in order to obtain the desired pulse shape. We used several algorithms to achieve this and the differences caused by the target pulse shape and duration are compared. It is found that the algorithm based on the ratio of the target pulse shape and measured pulse profile provides the most robust solution. The methods proposed here can be used to obtain any pulse shape with minimal knowledge of the laser amplification system.

The Discovery of Wild Date Palms in Oman Reveals a Complex Domestication History Involving Centers in the Middle East and Africa.

For many crops, wild relatives constitute an extraordinary resource for cultivar improvement [1, 2] and also help to better understand the history of their domestication [3]. However, the wild ancestor species of several perennial crops have not yet been identified. Perennial crops generally present a weak domestication syndrome allowing cultivated individuals to establish feral populations difficult to distinguish from truly wild populations, and there is frequently ongoing gene flow between wild relatives and the crop that might erode most genetic differences [4]. Here we report the discovery of populations of the wild ancestor species of the date palm (Phoenix dactylifera L.), one of the oldest and most important cultivated fruit plants in hot and arid regions of the Old World. We discovered these wild individuals in remote and isolated mountainous locations of Oman. They are genetically more diverse than and distinct from a representative sample of Middle Eastern cultivated date palms and exhibit rounded seed shapes resembling those of a close sister species and archeological samples, but not modern cultivars. Whole-genome sequencing of several wild and cultivated individuals revealed a complex domestication history involving the contribution of at least two wild sources to African cultivated date palms. The discovery of wild date palms offers a unique chance to further elucidate the history of this iconic crop that has constituted the cornerstone of traditional oasis polyculture systems for several thousand years [5].

Picosecond optical parametric chirped pulse amplifier as a preamplifier to generate high-energy seed pulses for contrast enhancement.

We present the design, implementation, and testing of a novel picosecond optical parametric preamplifier system to generate high-energy seed pulses for the Vulcan laser facility. The preamplifier amplifies 100 fs pulses stretched to 3 ps pulses from 10 pJ to 70 µJ in a single stage of amplification before the pulses are further amplified in the Vulcan high-power Nd:glass laser facility to the petawatt power level. This increased seed energy has led to an improvement of the nanosecond amplified spontaneous emission contrast intensity to 10(-10) of the main pulse, without degrading the output of the laser system.

Probe transit effect in interferometry of fast moving samples.

When a fast moving transparent sample (with a speed close to c) is probed with a laser pulse, some artifacts can occur from data analysis. These artifacts are connected to the transit time of the probe through the sample and can mask the presence of a steep gradient of refractive index in the sample. We study this problem in the case of interferometry. In fact, the problem can affect the femtosecond interferometry of the media under ultrafast ionization by a propagating laser pulse. Two algorithms are introduced: the first based on the phase difference and the second based on visibility. Both algorithms allow for the reconstruction, under suitable assumptions, of an approximated refractive index profile from the distorted fringes.