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Folate metabolism directly impacts nucleotide synthesis and methylation, which is of increasing interest in the reproductive medicine field. Studies assessing the genetic influence of folate metabolism on IVF treatments have currently been performed in women using their own oocytes. Most of these patients seeking to have a child or undergoing IVF treatments are advised to preventively intake folate supplies that restore known metabolic imbalances, but the treatments could lead to the promotion of specific enzymes in specific women, depending on their genetic variance. In the present study, we assess the influence of candidate gene variants related to folate metabolism, such as Serine Hydroxymethyltransferase 1 SHMT1 (rs1979276 and rs1979277), Betaine-Homocysteine S-Methyltransferase BHMT (rs3733890), Methionine synthase reductase MTRR (rs1801394), Methylenetetrahydrofolate reductase MTHFR (rs1801131 and rs1801133), methionine synthase MTR (rs12749581), ATP Binding Cassette Subfamily B Member 1 ABCB1 (rs1045642) and folate receptor alpha FOLR1 (rs2071010) on the success of IVF treatment performed in women being recipients of donated oocytes. The implication of such gene variants seems to have no direct impact on pregnancy consecution after IVF; however, several gene variants could influence pregnancy loss events or pregnancy maintenance, as consequence of folic acid fortification.<\/jats:p>","DOI":"10.3390\/ijms231911298","type":"journal-article","created":{"date-parts":[[2022,9,25]],"date-time":"2022-09-25T23:13:27Z","timestamp":1664147607000},"page":"11298","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Profiling the Influence of Gene Variants Related to Folate-Mediated One-Carbon Metabolism on the Outcome of In Vitro Fertilization (IVF) with Donor Oocytes in Recipients Receiving Folic Acid Fortification"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5820-3490","authenticated-orcid":false,"given":"Arturo Reyes","family":"Palomares","sequence":"first","affiliation":[{"name":"Laboratory of Translational Fertility Preservation, Department of Oncology and Pathology, Karolinska Institutet, 17164 Stockholm, Sweden"},{"name":"IVF Unit, Instituto de Fertilidad Cl\u00ednica Rinc\u00f3n, 29730 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maximiliano","family":"Ruiz-Galdon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Malaga, 29071 Malaga, Spain"},{"name":"Clinical Analysis Service, Hospital Regional Universitario de Malaga, 29010 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kui","family":"Liu","sequence":"additional","affiliation":[{"name":"Shenzhen Key Laboratory of Fertility Regulation, Center of Assisted Reproduction and Embryology, The University of Hong Kong-Shenzhen Hospital, Shenzhen 518000, China"},{"name":"Department of Obstetrics and Gynecology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 999077, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armando","family":"Reyes-Engel","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Malaga, 29071 Malaga, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4378-6181","authenticated-orcid":false,"given":"Kenny A.","family":"Rodriguez-Wallberg","sequence":"additional","affiliation":[{"name":"Laboratory of Translational Fertility Preservation, Department of Oncology and Pathology, Karolinska Institutet, 17164 Stockholm, Sweden"},{"name":"Section of Reproductive Medicine, Division of Gynecology and Reproduction, Karolinska University Hospital, Novumhuset Plan 4, 14186 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.ajog.2016.09.075","article-title":"Evidence That the Endometrial Microbiota Has an Effect on Implantation Success or Failure","volume":"215","author":"Moreno","year":"2016","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"818","DOI":"10.1016\/j.fertnstert.2013.05.004","article-title":"The Endometrial Receptivity Array for Diagnosis and Personalized Embryo Transfer as a Treatment for Patients with Repeated Implantation Failure","volume":"100","author":"Blesa","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/wsbm.72","article-title":"Gene-Environment Interactions, Folate Metabolism and the Embryonic Nervous System","volume":"2","author":"Ross","year":"2010","journal-title":"Wiley Interdiscip. Rev. Syst. Biol. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/0026-0495(94)90004-3","article-title":"Maternal Hyperhomocysteinemia: A Risk Factor for Neural-Tube Defects?","volume":"43","author":"Boers","year":"1994","journal-title":"Metabolism"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"15227","DOI":"10.1073\/pnas.93.26.15227","article-title":"Homocysteine Induces Congenital Defects of the Heart and Neural Tube: Effect of Folic Acid","volume":"93","author":"Rosenquist","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1096\/fj.14-261131","article-title":"Both the Folate Cycle and Betaine-Homocysteine Methyltransferase Contribute Methyl Groups for DNA Methylation in Mouse Blastocysts","volume":"29","author":"Zhang","year":"2015","journal-title":"FASEB J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1056\/NEJM199212243272602","article-title":"Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation","volume":"327","author":"Czeizel","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"(1991). Prevention of Neural Tube Defects: Results of the Medical Research Council Vitamin Study. Lancet, 338, 131\u2013137.","DOI":"10.1016\/0140-6736(91)90133-A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.7754\/Clin.Lab.2013.130914","article-title":"Differential Behavior of Serum and Red Blood Cell Folate during a Treatment with Levofolinic Acid. Gender Differences","volume":"60","author":"Lendinez","year":"2014","journal-title":"Clin. Lab."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1093\/humrep\/dem337","article-title":"Genotypes of the C677T and A1298C Polymorphisms of the MTHFR Gene as a Cause of Human Spontaneous Embryo Loss","volume":"22","author":"Palomares","year":"2007","journal-title":"Hum. Reprod."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1007\/s00439-016-1652-z","article-title":"Polymorphisms in the MTHFR Gene Influence Embryo Viability and the Incidence of Aneuploidy","volume":"135","author":"Enciso","year":"2016","journal-title":"Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Mayor-Olea, A., Callej\u00f3n, G., Palomares, A.R., Jim\u00e9nez, A.J., Gait\u00e1n, M.J., Rodr\u00edguez, A., Ruiz, M., and Reyes-Engel, A. (2008). Human Genetic Selection on the MTHFR 677C>T Polymorphism. BMC Med. Genet., 9.","DOI":"10.1186\/1471-2350-9-104"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1093\/ajcn\/nqaa259","article-title":"Knowledge Gaps in Understanding the Metabolic and Clinical Effects of Excess Folates\/Folic Acid: A Summary, and Perspectives, from an NIH Workshop","volume":"112","author":"Maruvada","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1643","DOI":"10.1515\/cclm-2012-0694","article-title":"Folic Acid Supplementation Does Not Reduce Intracellular Homocysteine, and May Disturb Intracellular One-Carbon Metabolism","volume":"51","author":"Smith","year":"2013","journal-title":"Clin. Chem. Lab Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10577","DOI":"10.1038\/ncomms10577","article-title":"Maternal Plasma Folate Impacts Differential DNA Methylation in an Epigenome-Wide Meta-Analysis of Newborns","volume":"7","author":"Joubert","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_16","first-page":"1","article-title":"Folic Acid Intervention during Pregnancy Alters DNA Methylation, Affecting Neural Target Genes through Two Distinct Mechanisms","volume":"14","author":"Irwin","year":"2022","journal-title":"Clin. Epigenetics"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/s41586-022-04549-9","article-title":"Reduced Reproductive Success Is Associated with Selective Constraint on Human Genes","volume":"603","author":"Gardner","year":"2022","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Palomares, A.R., Lend\u00ednez-Ram\u00edrez, A.M., P\u00e9rez-Nevot, B., Cort\u00e9s-Rodr\u00edguez, M., Mart\u00ednez, F., Garrido, N., Ruiz-Gald\u00f3n, M., and Reyes-Engel, A. (2013). Genetic Polymorphisms of Serotonin Transporter and Receptor 1A Could Influence Success during Embryo Implantation and Maintenance of Pregnancy. Fertil. Steril., 2009\u20132016.e2. 99.","DOI":"10.1016\/j.fertnstert.2013.02.026"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/j.rbmo.2017.03.011","article-title":"Fetal Alpha 5-Reductase Val89Leu Mutation Is Associated with Late Miscarriage","volume":"34","author":"Royo","year":"2017","journal-title":"Reprod. Biomed. Online"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"9761","DOI":"10.1073\/pnas.0904280106","article-title":"Single-Nucleotide Polymorphisms in the P53 Pathway Regulate Fertility in Humans","volume":"106","author":"Kang","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.1007\/s10815-021-02324-9","article-title":"Genetic Variants in the P53 Pathway Influence Implantation and Pregnancy Maintenance in IVF Treatments Using Donor Oocytes","volume":"38","author":"Palomares","year":"2021","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"R963","DOI":"10.1152\/ajpregu.00173.2005","article-title":"P-Glycoprotein and Breast Cancer Resistance Protein Expression in Human Placentae of Various Gestational Ages","volume":"289","author":"Mathias","year":"2005","journal-title":"Am. J. Physiol. Regul. Integr. Comp. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/j.placenta.2005.05.007","article-title":"Expression of the Multidrug Resistance P-Glycoprotein, (ABCB1 Glycoprotein) in the Human Placenta Decreases with Advancing Gestation","volume":"27","author":"Sun","year":"2006","journal-title":"Placenta"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1080\/17425255.2018.1499726","article-title":"An Update on Expression and Function of P-Gp\/Abcb1 and Bcrp\/Abcg2 in the Placenta and Fetus","volume":"14","author":"Han","year":"2018","journal-title":"Expert Opin. Drug. Metab. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"534","DOI":"10.3109\/10715762.2014.891735","article-title":"Association of Oxidative Stress-Related Genes with Idiopathic Recurrent Miscarriage","volume":"48","author":"Khadzhieva","year":"2014","journal-title":"Free Radic. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2088","DOI":"10.1002\/ajmg.a.33036","article-title":"Maternal Medication Use, Carriership of the ABCB1 3435C > T Polymorphism and the Risk of a Child with Cleft Lip with or without Cleft Palate","volume":"149A","author":"Bliek","year":"2009","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1073\/pnas.97.7.3473","article-title":"Functional Polymorphisms of the Human Multidrug-Resistance Gene: Multiple Sequence Variations and Correlation of One Allele with P-Glycoprotein Expression and Activity in Vivo","volume":"97","author":"Hoffmeyer","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1095\/biolreprod.110.088351","article-title":"Possible Roles for Folic Acid in the Regulation of Trophoblast Invasion and Placental Development in Normal Early Human Pregnancy","volume":"84","author":"Williams","year":"2011","journal-title":"Biol. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"236.e1","DOI":"10.1016\/j.ajog.2010.10.911","article-title":"General Maternal Medication Use, Folic Acid, the MDR1 C3435T Polymorphism, and the Risk of a Child with a Congenital Heart Defect","volume":"204","author":"Isaacs","year":"2011","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1111\/j.1399-0004.2006.00618.x","article-title":"Maternal MTR Genotype Contributes to the Risk of Non-Syndromic Cleft Lip and Palate in the Polish Population","volume":"69","author":"Mostowska","year":"2006","journal-title":"Clin. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1002\/ajmg.a.20234","article-title":"Methionine Synthase (MTR) 2756 (A\u2009\u2192\u2009G) Polymorphism, Double Heterozygosity Methionine Synthase 2756 AG\/Methionine Synthase Reductase (MTRR) 66 AG, and Elevated Homocysteinemia Are Three Risk Factors for Having a Child with Down Syndrome","volume":"121A","author":"Bosco","year":"2003","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1086\/344209","article-title":"Maternal Genetic Effects, Exerted by Genes Involved in Homocysteine Remethylation, Influence the Risk of Spina Bifida","volume":"71","author":"Doolin","year":"2002","journal-title":"Am. J. Hum. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1006\/mgme.2001.3175","article-title":"Is Mutated Serine Hydroxymethyltransferase (SHMT) Involved in the Etiology of Neural Tube Defects?","volume":"73","author":"Heil","year":"2001","journal-title":"Mol. Genet. Metab."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1002\/bdr2.23623","article-title":"Interaction between Maternal and Paternal SHMT1 C1420T Predisposes to Neural Tube Defects in the Fetus: Evidence from Case\u2013Control and Family-Based Triad Approaches","volume":"109","author":"Rebekah","year":"2017","journal-title":"Birth Defects Res."},{"key":"ref_35","first-page":"1067","article-title":"Maternal Polymorphic Loci of Rs1979277 Serine Hydroxymethyl Transferase and Rs1805087 5-Methylenetetrahydrofolate Are Correlated with the Development of Fetal Growth Restriction: A Case-Control Study","volume":"19","author":"Efremova","year":"2021","journal-title":"Int. J. Reprod. Biomed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1111\/odi.13229","article-title":"A SHMT1 Variant Decreases the Risk of Nonsyndromic Cleft Lip with or without Cleft Palate in Chile","volume":"26","author":"Salamanca","year":"2020","journal-title":"Oral Dis."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Obeid, R. (2013). The Metabolic Burden of Methyl Donor Deficiency with Focus on the Betaine Homocysteine Methyltransferase Pathway. Nutrients, 5.","DOI":"10.3390\/nu5093481"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/0003-9861(72)90451-1","article-title":"Methionine Metabolism in Mammals: Kinetic Study of Betaine-Homocysteine Methyltransferase","volume":"153","author":"Finkelstein","year":"1972","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.ymgme.2008.03.013","article-title":"Human Betaine-Homocysteine Methyltransferase (BHMT) and BHMT2: Common Gene Sequence Variation and Functional Characterization","volume":"94","author":"Li","year":"2008","journal-title":"Mol. Genet. Metab."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5225","DOI":"10.2147\/OTT.S102452","article-title":"Association between BHMT Gene Rs3733890 Polymorphism and Cancer Risk: Evidence from a Meta-Analysis","volume":"9","author":"Xu","year":"2016","journal-title":"Onco Targets Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0021-9150(03)00010-8","article-title":"Investigations of a Common Genetic Variant in Betaine\u2013Homocysteine Methyltransferase (BHMT) in Coronary Artery Disease","volume":"167","author":"Weisberg","year":"2003","journal-title":"Atherosclerosis"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1002\/ajmg.a.20115","article-title":"Common Variant in Betaine-Homocysteine Methyltransferase (BHMT) and Risk for Spina Bifida","volume":"119A","author":"Morin","year":"2003","journal-title":"Am. J. Med. Genet. A"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1002\/humu.20522","article-title":"Large-Scale Population-Based Metabolic Phenotyping of Thirteen Genetic Polymorphisms Related to One-Carbon Metabolism","volume":"28","author":"Fredriksen","year":"2007","journal-title":"Hum. Mutat."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"560183","DOI":"10.1155\/2014\/560183","article-title":"The Effect of Multiple Single Nucleotide Polymorphisms in the Folic Acid Pathway Genes on Homocysteine Metabolism","volume":"2014","author":"Liang","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Colomina, J.M., Cavall\u00e9-Busquets, P., Fern\u00e0ndez-Roig, S., Sol\u00e9-Navais, P., Fernandez-Ballart, J.D., Ballesteros, M., Ueland, P.M., Meyer, K., and Murphy, M.M. (2016). Maternal Folate Status and the BHMT c.716G>A Polymorphism Affect the Betaine Dimethylglycine Pathway during Pregnancy. Nutrients, 8.","DOI":"10.3390\/nu8100621"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ymgme.2007.02.004","article-title":"Polymorphisms in Methionine Synthase Reductase and Betaine-Homocysteine S-Methyltransferase Genes: Risk of Placental Abruption","volume":"91","author":"Ananth","year":"2007","journal-title":"Mol. Genet. Metab."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1289\/ehp.9166","article-title":"Neural Tube Defects and Folate Pathway Genes: Family-Based Association Tests of Gene-Gene and Gene-Environment Interactions","volume":"114","author":"Boyles","year":"2006","journal-title":"Environ. Health Perspect."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.jns.2013.11.017","article-title":"Investigations of Single Nucleotide Polymorphisms in Folate Pathway Genes in Chinese Families with Neural Tube Defects","volume":"337","author":"Liu","year":"2014","journal-title":"J. Neurol. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Zeng, H., Liu, Z., Zhang, L., and Liu, N. (2022). MTHFR 677TT Is Associated with Decreased Number of Embryos and Cumulative Live Birth Rate in Patients Undergoing GnRHa Short Protocol: A Retrospective Study. BMC Pregnancy Childbirth, 22.","DOI":"10.1186\/s12884-022-04506-4"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1210\/me.2011-1196","article-title":"Research Resource: Interactome of Human Embryo Implantation: Identification of Gene Expression Pathways, Regulation, and Integrated Regulatory Networks","volume":"26","author":"Reimand","year":"2012","journal-title":"Mol. Endocrinol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/aogs.12522","article-title":"Folic Acid Supplementation and Methylenetetrahydrofolate Reductase (MTHFR) Gene Variations in Relation to in Vitro Fertilization Pregnancy Outcome","volume":"94","author":"Murto","year":"2015","journal-title":"Acta Obstet. Gynecol. Scand."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1080\/19396368.2021.1923861","article-title":"Methylenetetrahydrofolate Reductase Gene Polymorphisms Are Not Associated with Embryo Chromosomal Abnormalities and IVF Outcomes","volume":"67","author":"Morales","year":"2021","journal-title":"Syst. Biol. Reprod. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1007\/s43032-020-00161-2","article-title":"Maternal Folic Acid Supplementation Mediates Offspring Health via DNA Methylation","volume":"27","author":"Liu","year":"2020","journal-title":"Reprod. Sci."},{"key":"ref_54","first-page":"2","article-title":"Criterios de Valoraci\u00f3n Morfol\u00f3gicos de Oocitos, Preembriones Tempranos y Blastocistos Humanos Propuestos Por ASEBIR","volume":"13","author":"Ligero","year":"2008","journal-title":"ASEBIR"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1093\/humrep\/dei167","article-title":"Updated and Revised Nomenclature for Description of Early Pregnancy Events","volume":"20","author":"Farquharson","year":"2005","journal-title":"Hum. Reprod."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/humrep\/deu299","article-title":"Terminology for Pregnancy Loss Prior to Viability: A Consensus Statement from the ESHRE Early Pregnancy Special Interest Group","volume":"30","author":"Kolte","year":"2015","journal-title":"Hum. Reprod."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1038\/nature11632","article-title":"An Integrated Map of Genetic Variation from 1,092 Human Genomes","volume":"491","author":"Abecasis","year":"2012","journal-title":"Nature"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1093\/bioinformatics\/btm025","article-title":"SNPassoc: An R Package to Perform Whole Genome Association Studies","volume":"23","author":"Armengol","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1093\/bioinformatics\/btl268","article-title":"SNPStats: A Web Tool for the Analysis of Association Studies","volume":"22","author":"Valls","year":"2006","journal-title":"Bioinformatics"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11298\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:39:06Z","timestamp":1760143146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/19\/11298"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,25]]},"references-count":59,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["ijms231911298"],"URL":"https:\/\/doi.org\/10.3390\/ijms231911298","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,25]]}}}