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-genetic08208nas 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-severity