@article {770, title = {A Comprehensive Analysis of 21 Actionable Pharmacogenes in the Spanish Population: From Genetic Characterisation to Clinical Impact.}, journal = {Pharmaceutics}, volume = {15}, year = {2023}, month = {2023 Apr 19}, abstract = {

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.

}, issn = {1999-4923}, doi = {10.3390/pharmaceutics15041286}, author = {N{\'u}{\~n}ez-Torres, Roc{\'\i}o and Pita, Guillermo and Pe{\~n}a-Chilet, Maria and L{\'o}pez-L{\'o}pez, Daniel and Zamora, Jorge and Rold{\'a}n, Gema and Herr{\'a}ez, Bel{\'e}n and Alvarez, Nuria and Alonso, Mar{\'\i}a Rosario and Dopazo, Joaquin and Gonz{\'a}lez-Neira, Anna} } @article {769, title = {A crowdsourcing database for the copy-number variation of the Spanish population.}, journal = {Hum Genomics}, volume = {17}, year = {2023}, month = {2023 Mar 09}, pages = {20}, abstract = {

BACKGROUND: 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.

RESULTS: 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/ .

CONCLUSION: 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.

}, issn = {1479-7364}, doi = {10.1186/s40246-023-00466-8}, author = {L{\'o}pez-L{\'o}pez, Daniel and Rold{\'a}n, Gema and Fernandez-Rueda, Jose L and Bostelmann, Gerrit and Carmona, Rosario and Aquino, Virginia and Perez-Florido, Javier and Ortuno, Francisco and Pita, Guillermo and N{\'u}{\~n}ez-Torres, Roc{\'\i}o and Gonz{\'a}lez-Neira, Anna and Pe{\~n}a-Chilet, Maria and Dopazo, Joaquin} } @article {760, title = {Novel genes and sex differences in COVID-19 severity.}, journal = {Hum Mol Genet}, year = {2022}, month = {2022 Jun 16}, abstract = {

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.

}, issn = {1460-2083}, doi = {10.1093/hmg/ddac132}, author = {Cruz, Raquel and Almeida, Silvia Diz-de and Heredia, Miguel L{\'o}pez and Quintela, In{\'e}s and Ceballos, Francisco C and Pita, Guillermo and Lorenzo-Salazar, Jos{\'e} M and Gonz{\'a}lez-Montelongo, Rafaela and Gago-Dom{\'\i}nguez, Manuela and Porras, Marta Sevilla and Casta{\~n}o, Jair Antonio Tenorio and Nevado, Juli{\'a}n and Aguado, Jose Mar{\'\i}a and Aguilar, Carlos and Aguilera-Albesa, Sergio and Almadana, Virginia and Almoguera, Berta and Alvarez, Nuria and Andreu-Bernabeu, {\'A}lvaro and Arana-Arri, Eunate and Arango, Celso and Arranz, Mar{\'\i}a J and Artiga, Maria-Jesus and Baptista-Rosas, Ra{\'u}l C and Barreda-S{\'a}nchez, Mar{\'\i}a and Belhassen-Garcia, Moncef and Bezerra, Joao F and Bezerra, Marcos A C and Boix-Palop, Luc{\'\i}a and Bri{\'o}n, Maria and Brugada, Ram{\'o}n and Bustos, Matilde and Calder{\'o}n, Enrique J and Carbonell, Cristina and Castano, Luis and Castelao, Jose E and Conde-Vicente, Rosa and Cordero-Lorenzana, M Lourdes and Cortes-Sanchez, Jose L and Corton, Marta and Darnaude, M Teresa and De Martino-Rodr{\'\i}guez, Alba and Campo-P{\'e}rez, Victor and Bustamante, Aranzazu Diaz and Dom{\'\i}nguez-Garrido, Elena and Luchessi, Andr{\'e} D and Eir{\'o}s, Roc{\'\i}o and Sanabria, Gladys Mercedes Estigarribia and Fari{\~n}as, Mar{\'\i}a Carmen and Fern{\'a}ndez-Robelo, Ux{\'\i}a and Fern{\'a}ndez-Rodr{\'\i}guez, Amanda and Fern{\'a}ndez-Villa, Tania and Gil-Fournier, Bel{\'e}n and G{\'o}mez-Arrue, Javier and {\'A}lvarez, Beatriz Gonz{\'a}lez and Quir{\'o}s, Fernan Gonzalez Bernaldo and Gonz{\'a}lez-Pe{\~n}as, Javier and Guti{\'e}rrez-Bautista, Juan F and Herrero, Mar{\'\i}a Jos{\'e} and Herrero-Gonzalez, Antonio and Jimenez-Sousa, Mar{\'\i}a A and Lattig, Mar{\'\i}a Claudia and Borja, Anabel Liger and Lopez-Rodriguez, Rosario and Mancebo, Esther and Mart{\'\i}n-L{\'o}pez, Caridad and Mart{\'\i}n, Vicente and Martinez-Nieto, Oscar and Martinez-Lopez, Iciar and Martinez-Resendez, Michel F and Martinez-Perez, {\'A}ngel and Mazzeu, Juliana A and Mac{\'\i}as, Eleuterio Merayo and Minguez, Pablo and Cuerda, Victor Moreno and Silbiger, Vivian N and Oliveira, Silviene F and Ortega-Paino, Eva and Parellada, Mara and Paz-Artal, Estela and Santos, Ney P C and P{\'e}rez-Matute, Patricia and Perez, Patricia and P{\'e}rez-Tom{\'a}s, M Elena and Perucho, Teresa and Pinsach-Abuin, Mel Lina and Pompa-Mera, Ericka N and Porras-Hurtado, Gloria L and Pujol, Aurora and Le{\'o}n, Soraya Ramiro and Resino, Salvador and Fernandes, Marianne R and Rodr{\'\i}guez-Ruiz, Emilio and Rodriguez-Artalejo, Fernando and Rodriguez-Garcia, Jos{\'e} A and Ruiz-Cabello, Francisco and Ruiz-Hornillos, Javier and Ryan, Pablo and Soria, Jos{\'e} Manuel and Souto, Juan Carlos and Tamayo, Eduardo and Tamayo-Velasco, Alvaro and Taracido-Fernandez, Juan Carlos and Teper, Alejandro and Torres-Tobar, Lilian and Urioste, Miguel and Valencia-Ramos, Juan and Y{\'a}{\~n}ez, Zuleima and Zarate, Ruth and Nakanishi, Tomoko and Pigazzini, Sara and Degenhardt, Frauke and Butler-Laporte, Guillaume and Maya-Miles, Douglas and Bujanda, Luis and Bouysran, Youssef and Palom, Adriana and Ellinghaus, David and Mart{\'\i}nez-Bueno, Manuel and Rolker, Selina and Amitrano, Sara and Roade, Luisa and Fava, Francesca and Spinner, Christoph D and Prati, Daniele and Bernardo, David and Garc{\'\i}a, Federico and Darcis, Gilles and Fern{\'a}ndez-Cadenas, Israel and Holter, Jan Cato and Banales, Jesus M and Frithiof, Robert and Duga, Stefano and Asselta, Rosanna and Pereira, Alexandre C and Romero-G{\'o}mez, Manuel and Nafr{\'\i}a-Jim{\'e}nez, Beatriz and Hov, Johannes R and Migeotte, Isabelle and Renieri, Alessandra and Planas, Anna M and Ludwig, Kerstin U and Buti, Maria and Rahmouni, Souad and Alarc{\'o}n-Riquelme, Marta E and Schulte, Eva C and Franke, Andre and Karlsen, Tom H and Valenti, Luca and Zeberg, Hugo and Richards, Brent and Ganna, Andrea and Boada, Merc{\`e} and Rojas, Itziar and Ruiz, Agust{\'\i}n and S{\'a}nchez, Pascual and Real, Luis Miguel and Guill{\'e}n-Navarro, Encarna and Ayuso, Carmen and Gonz{\'a}lez-Neira, Anna and Riancho, Jos{\'e} A and Rojas-Martinez, Augusto and Flores, Carlos and Lapunzina, Pablo and Carracedo, {\'A}ngel} } @article {701, title = {CSVS, a crowdsourcing database of the Spanish population genetic variability.}, journal = {Nucleic Acids Res}, volume = {49}, year = {2021}, month = {2021 01 08}, pages = {D1130-D1137}, abstract = {

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/.

}, keywords = {Alleles, Chromosome Mapping, Crowdsourcing, Databases, Genetic, Exome, Gene Frequency, Genetic Variation, Genetics, Population, Genome, Human, Genomics, Humans, Internet, Precision Medicine, Software, Spain}, issn = {1362-4962}, doi = {10.1093/nar/gkaa794}, author = {Pe{\~n}a-Chilet, Maria and Rold{\'a}n, Gema and Perez-Florido, Javier and Ortuno, Francisco M and Carmona, Rosario and Aquino, Virginia and L{\'o}pez-L{\'o}pez, Daniel and Loucera, Carlos and Fernandez-Rueda, Jose L and Gallego, Asunci{\'o}n and Garcia-Garcia, Francisco and Gonz{\'a}lez-Neira, Anna and Pita, Guillermo and N{\'u}{\~n}ez-Torres, Roc{\'\i}o and Santoyo-L{\'o}pez, Javier and Ayuso, Carmen and Minguez, Pablo and Avila-Fernandez, Almudena and Corton, Marta and Moreno-Pelayo, Miguel {\'A}ngel and Morin, Mat{\'\i}as and Gallego-Martinez, Alvaro and Lopez-Escamez, Jose A and Borrego, Salud and Anti{\v n}olo, Guillermo and Amigo, Jorge and Salgado-Garrido, Josefa and Pasalodos-Sanchez, Sara and Morte, Beatriz and Carracedo, {\'A}ngel and Alonso, {\'A}ngel and Dopazo, Joaquin} } @article {939, title = {Select your SNPs (SYSNPs): a web tool for automatic and massive selection of SNPs.}, journal = {International journal of data mining and bioinformatics}, volume = {6}, year = {2012}, month = {2012}, pages = {324-34}, abstract = {Association 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{\textquoteright} 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.}, issn = {1748-5673}, url = {http://inderscience.metapress.com/content/f76740x8071u513n/}, author = {Lorente-Galdos, Bel{\'e}n and Medina, Ignacio and Morcillo-Suarez, Carlos and Heredia, Txema and Carre{\~n}o-Torres, Angel and Sangr{\'o}s, Ricardo and Alegre, Josep and Pita, Guillermo and Vellalta, Gemma and Malats, Nuria and Pisano, David G and Joaqu{\'\i}n Dopazo and Navarro, Arcadi} }