02245nas a2200253   4500008004100000022001400041245013700055210006900192260001600261490000700277520134400284100002701628700002001655700002401675700002601699700001801725700001801743700002101761700001901782700002801801700002001829700002601849856011601875       2023                        eng d  a1999-492300aA Comprehensive Analysis of 21 Actionable Pharmacogenes in the Spanish Population: From Genetic Characterisation to Clinical Impact.0 aComprehensive Analysis of 21 Actionable Pharmacogenes in the Spa  c2023 Apr 190 v153 a<p>The implementation of pharmacogenetics (PGx) is a main milestones of precision medicine nowadays in order to achieve safer and more effective therapies. Nevertheless, the implementation of PGx diagnostics is extremely slow and unequal worldwide, in part due to a lack of ethnic PGx information. We analysed genetic data from 3006 Spanish individuals obtained by different high-throughput (HT) techniques. Allele frequencies were determined in our population for the main 21 actionable PGx genes associated with therapeutical changes. We found that 98% of the Spanish population harbours at least one allele associated with a therapeutical change and, thus, there would be a need for a therapeutical change in a mean of 3.31 of the 64 associated drugs. We also identified 326 putative deleterious variants that were not previously related with PGx in 18 out of the 21 main PGx genes evaluated and a total of 7122 putative deleterious variants for the 1045 PGx genes described. Additionally, we performed a comparison of the main HT diagnostic techniques, revealing that after whole genome sequencing, genotyping with the PGx HT array is the most suitable solution for PGx diagnostics. Finally, all this information was integrated in the Collaborative Spanish Variant Server to be available to and updated by the scientific community.</p>1 aNúñez-Torres, Rocío1 aPita, Guillermo1 aPeña-Chilet, Maria1 aLópez-López, Daniel1 aZamora, Jorge1 aRoldán, Gema1 aHerráez, Belén1 aAlvarez, Nuria1 aAlonso, María, Rosario1 aDopazo, Joaquin1 aGonzález-Neira, Anna  uhttp://clinbioinfosspa.es/content/comprehensive-analysis-21-actionable-pharmacogenes-spanish-population-genetic02663nas a2200301   4500008004100000022001400041245008600055210006900141260001600210300000700226490000700233520168700240100002601927700001801953700002901971700002302000700002102023700002102044700002602065700002202091700002002113700002702133700002602160700002402186700002002210710002902230856010202259       2023                        eng d  a1479-736400aA crowdsourcing database for the copy-number variation of the Spanish population.0 acrowdsourcing database for the copynumber variation of the Spani  c2023 Mar 09  a200 v173 a<p><b>BACKGROUND: </b>Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants.</p><p><b>RESULTS: </b>Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/ .</p><p><b>CONCLUSION: </b>SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database.</p>1 aLópez-López, Daniel1 aRoldán, Gema1 aFernandez-Rueda, Jose, L1 aBostelmann, Gerrit1 aCarmona, Rosario1 aAquino, Virginia1 aPerez-Florido, Javier1 aOrtuno, Francisco1 aPita, Guillermo1 aNúñez-Torres, Rocío1 aGonzález-Neira, Anna1 aPeña-Chilet, Maria1 aDopazo, Joaquin1 aCSVS Crowdsourcing Group  uhttp://clinbioinfosspa.es/content/crowdsourcing-database-copy-number-variation-spanish-population08208nas a2202125   4500008004100000022001400041245005800055210005600113260001600169520175300185100001701938700002901955700002801984700002002012700002702032700002002059700003002079700003402109700002902143700002702172700003102199700002002230700002502250700002002275700002802295700002302323700002102346700001902367700002902386700002302415700001802438700002202456700002402478700002902502700002902531700002902560700002102589700002502610700002302635700001802658700002002676700002002696700002602716700002402742700001802766700002202784700002402806700003102830700002802861700001802889700002102907700003202928700002502960700003102985700003003016700002403046700001903070700003303089700002903122700002903151700003403180700002803214700002503242700002503267700003303292700003203325700002903357700003303386700002703419700003003446700002903476700002803505700002503533700002903558700002003587700002803607700002103635700002603656700002603682700003303708700002703741700002303768700003103791700001903822700002703841700002403868700002603892700002203918700002003940700002203960700002103982700002804003700002004031700002504051700002004076700002904096700002604125700003004151700001804181700002604199700002104225700002704246700002804273700003304301700003104334700002804365700002704393700001604420700002504436700002404461700002004485700002704505700003704532700002104569700002504590700002004615700002504635700002104660700001704681700002204698700002004720700002304740700003004763700002404793700001804817700002204835700001904857700002204876700002804898700001904926700001904945700001704964700002004981700002605001700001905027700002005046700002205066700001905088700003105107700002205138700002205160700002105182700001805203700002105221700002605242700002605268700003005294700002105324700002305345700002405368700002005392700002305412700001605435700002005451700003205471700002005503700001805523700002005541700001805561700001705579700002005596700001805616700001805634700001805652700001905670700002205689700002305711700003005734700001805764700002605782700002205808700002805830700001905858700002105877700002205898710002505920710002505945710002405970856008805994       2022                        eng d  a1460-208300aNovel genes and sex differences in COVID-19 severity.0 aNovel genes and sex differences in COVID19 severity  c2022 Jun 163 a<p>Here we describe the results of a genome-wide study conducted in 11 939 COVID-19 positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (p < 5x10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (p = 1.3x10-22 and p = 8.1x10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (p = 4.4x10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (p = 2.7x10-8) and ARHGAP33 (p = 1.3x10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, p = 4.1x10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥ 60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.</p>1 aCruz, Raquel1 ade Almeida, Silvia, Diz-1 aHeredia, Miguel, López1 aQuintela, Inés1 aCeballos, Francisco, C1 aPita, Guillermo1 aLorenzo-Salazar, José, M1 aGonzález-Montelongo, Rafaela1 aGago-Domínguez, Manuela1 aPorras, Marta, Sevilla1 aCastaño, Jair, Antonio Te1 aNevado, Julián1 aAguado, Jose, María1 aAguilar, Carlos1 aAguilera-Albesa, Sergio1 aAlmadana, Virginia1 aAlmoguera, Berta1 aAlvarez, Nuria1 aAndreu-Bernabeu, Álvaro1 aArana-Arri, Eunate1 aArango, Celso1 aArranz, María, J1 aArtiga, Maria-Jesus1 aBaptista-Rosas, Raúl, C1 aBarreda-Sánchez, María1 aBelhassen-Garcia, Moncef1 aBezerra, Joao, F1 aBezerra, Marcos, A C1 aBoix-Palop, Lucía1 aBrión, Maria1 aBrugada, Ramón1 aBustos, Matilde1 aCalderón, Enrique, J1 aCarbonell, Cristina1 aCastano, Luis1 aCastelao, Jose, E1 aConde-Vicente, Rosa1 aCordero-Lorenzana, Lourdes1 aCortes-Sanchez, Jose, L1 aCorton, Marta1 aDarnaude, Teresa1 aDe Martino-Rodríguez, Alba1 aCampo-Pérez, Victor1 aBustamante, Aranzazu, Diaz1 aDomínguez-Garrido, Elena1 aLuchessi, André, D1 aEirós, Rocío1 aSanabria, Gladys, Mercedes E1 aFariñas, María, Carmen1 aFernández-Robelo, Uxía1 aFernández-Rodríguez, Amanda1 aFernández-Villa, Tania1 aGil-Fournier, Belén1 aGómez-Arrue, Javier1 aÁlvarez, Beatriz, González1 aQuirós, Fernan, Gonzalez B1 aGonzález-Peñas, Javier1 aGutiérrez-Bautista, Juan, F1 aHerrero, María, José1 aHerrero-Gonzalez, Antonio1 aJimenez-Sousa, María, A1 aLattig, María, Claudia1 aBorja, Anabel, Liger1 aLopez-Rodriguez, Rosario1 aMancebo, Esther1 aMartín-López, Caridad1 aMartín, Vicente1 aMartinez-Nieto, Oscar1 aMartinez-Lopez, Iciar1 aMartinez-Resendez, Michel, F1 aMartinez-Perez, Ángel1 aMazzeu, Juliana, A1 aMacías, Eleuterio, Merayo1 aMinguez, Pablo1 aCuerda, Victor, Moreno1 aSilbiger, Vivian, N1 aOliveira, Silviene, F1 aOrtega-Paino, Eva1 aParellada, Mara1 aPaz-Artal, Estela1 aSantos, Ney, P C1 aPérez-Matute, Patricia1 aPerez, Patricia1 aPérez-Tomás, Elena1 aPerucho, Teresa1 aPinsach-Abuin, Mel, Lina1 aPompa-Mera, Ericka, N1 aPorras-Hurtado, Gloria, L1 aPujol, Aurora1 aLeón, Soraya, Ramiro1 aResino, Salvador1 aFernandes, Marianne, R1 aRodríguez-Ruiz, Emilio1 aRodriguez-Artalejo, Fernando1 aRodriguez-Garcia, José, A1 aRuiz-Cabello, Francisco1 aRuiz-Hornillos, Javier1 aRyan, Pablo1 aSoria, José, Manuel1 aSouto, Juan, Carlos1 aTamayo, Eduardo1 aTamayo-Velasco, Alvaro1 aTaracido-Fernandez, Juan, Carlos1 aTeper, Alejandro1 aTorres-Tobar, Lilian1 aUrioste, Miguel1 aValencia-Ramos, Juan1 aYáñez, Zuleima1 aZarate, Ruth1 aNakanishi, Tomoko1 aPigazzini, Sara1 aDegenhardt, Frauke1 aButler-Laporte, Guillaume1 aMaya-Miles, Douglas1 aBujanda, Luis1 aBouysran, Youssef1 aPalom, Adriana1 aEllinghaus, David1 aMartínez-Bueno, Manuel1 aRolker, Selina1 aAmitrano, Sara1 aRoade, Luisa1 aFava, Francesca1 aSpinner, Christoph, D1 aPrati, Daniele1 aBernardo, David1 aGarcía, Federico1 aDarcis, Gilles1 aFernández-Cadenas, Israel1 aHolter, Jan, Cato1 aBanales, Jesus, M1 aFrithiof, Robert1 aDuga, Stefano1 aAsselta, Rosanna1 aPereira, Alexandre, C1 aRomero-Gómez, Manuel1 aNafría-Jiménez, Beatriz1 aHov, Johannes, R1 aMigeotte, Isabelle1 aRenieri, Alessandra1 aPlanas, Anna, M1 aLudwig, Kerstin, U1 aButi, Maria1 aRahmouni, Souad1 aAlarcón-Riquelme, Marta, E1 aSchulte, Eva, C1 aFranke, Andre1 aKarlsen, Tom, H1 aValenti, Luca1 aZeberg, Hugo1 aRichards, Brent1 aGanna, Andrea1 aBoada, Mercè1 aRojas, Itziar1 aRuiz, Agustín1 aSánchez, Pascual1 aReal, Luis, Miguel1 aGuillén-Navarro, Encarna1 aAyuso, Carmen1 aGonzález-Neira, Anna1 aRiancho, José, A1 aRojas-Martinez, Augusto1 aFlores, Carlos1 aLapunzina, Pablo1 aCarracedo, Ángel1 aSCOURGE Cohort Group1 aHOSTAGE Cohort Group1 aGRA@CE Cohort Group  uhttp://clinbioinfosspa.es/content/novel-genes-and-sex-differences-covid-19-severity03503nas a2200709   4500008004100000022001400041245008200055210006900137260001500206300001600221490000700237520139500244653001201639653002301651653001801674653002301692653001001715653001901725653002201744653002501766653001801791653001301809653001101822653001301833653002301846653001301869653001001882100002401892700001801916700002601934700002501960700002101985700002102006700002602027700002002053700002902073700002302102700002902125700002602154700002002180700002702200700002702227700001802254700001902272700003002291700001802321700003402339700001902373700002902392700002702421700001902448700002502467700001702492700002802509700002802537700001902565700002202584700001902606700002002625710004302645856010502688       2021                        eng d  a1362-496200aCSVS, a crowdsourcing database of the Spanish population genetic variability.0 aCSVS a crowdsourcing database of the Spanish population genetic   c2021 01 08  aD1130-D11370 v493 a<p>The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variability worldwide. CSVS is also part of the GA4GH Beacon network. CSVS can be accessed at: http://csvs.babelomics.org/.</p>10aAlleles10aChromosome Mapping10aCrowdsourcing10aDatabases, Genetic10aExome10aGene Frequency10aGenetic Variation10aGenetics, Population10aGenome, Human10aGenomics10aHumans10aInternet10aPrecision Medicine10aSoftware10aSpain1 aPeña-Chilet, Maria1 aRoldán, Gema1 aPerez-Florido, Javier1 aOrtuno, Francisco, M1 aCarmona, Rosario1 aAquino, Virginia1 aLópez-López, Daniel1 aLoucera, Carlos1 aFernandez-Rueda, Jose, L1 aGallego, Asunción1 aGarcia-Garcia, Francisco1 aGonzález-Neira, Anna1 aPita, Guillermo1 aNúñez-Torres, Rocío1 aSantoyo-López, Javier1 aAyuso, Carmen1 aMinguez, Pablo1 aAvila-Fernandez, Almudena1 aCorton, Marta1 aMoreno-Pelayo, Miguel, Ángel1 aMorin, Matías1 aGallego-Martinez, Alvaro1 aLopez-Escamez, Jose, A1 aBorrego, Salud1 aAntiňolo, Guillermo1 aAmigo, Jorge1 aSalgado-Garrido, Josefa1 aPasalodos-Sanchez, Sara1 aMorte, Beatriz1 aCarracedo, Ángel1 aAlonso, Ángel1 aDopazo, Joaquin1 aSpanish Exome Crowdsourcing Consortium  uhttp://clinbioinfosspa.es/content/csvs-crowdsourcing-database-spanish-population-genetic-variability01878nas a2200289   4500008004100000022001400041245008700055210006900142260000900211300001100220490000600231520100600237100002701243700002001270700002801290700001901318700002701337700002201364700001801386700002001404700002001424700001801444700002101462700002101483700002001504856006401524       2012                        eng d  a1748-567300aSelect your SNPs (SYSNPs): a web tool for automatic and massive selection of SNPs.0 aSelect your SNPs SYSNPs a web tool for automatic and massive sel  c2012  a324-340 v63 aAssociation studies are the choice approach in the discovery of the genomic basis of complex traits. To carry out such analysis, researchers frequently need to (1) select optimally informative sets of Single Nucleotide Polymorphisms (SNPs) in candidate regions and (2) annotate the results of associations found by means of genome-wide SNP arrays. These are complex tasks, since many criteria have to be considered, including the SNPs’ functional properties, technological information and haplotype frequencies in given populations. SYSNPs implements algorithms that allow for efficient and simultaneous consideration of all the relevant criteria to obtain sets of SNPs that properly cover arbitrarily large lists of genes or genomic regions. Complementarily, SYSNPs allows for comprehensive functional annotation of SNPs linked to any given marker SNP. SYSNPs dramatically reduces the effort needed for SNP selection from days of searching various databases to a few minutes using a simple browser.1 aLorente-Galdos, Belén1 aMedina, Ignacio1 aMorcillo-Suarez, Carlos1 aHeredia, Txema1 aCarreño-Torres, Angel1 aSangrós, Ricardo1 aAlegre, Josep1 aPita, Guillermo1 aVellalta, Gemma1 aMalats, Nuria1 aPisano, David, G1 aDopazo, Joaquín1 aNavarro, Arcadi  uhttp://inderscience.metapress.com/content/f76740x8071u513n/