{"doi":"10.1111/andr.70073","title":"The rising role of genetics in andrology research and clinical practice","abstract":"The term “androgenetics” refers to research focusing on genetics of male-specific conditions.1 For the first time, Andrology publishes a Special Issue “Genetics in Andrology” solely devoted to androgenetics—a forward-looking milestone in the field. So far, andrology has lagged behind other medical fields in taking advantage of rapid technological (r)evolution and recent breakthroughs in genetics and genomics. In this Special Issue, 10 review articles and 15 original studies authored by researchers from around the world provide a comprehensive overview of the state-of-the-art, current, and perspective clinical applications of genetics in andrology. To facilitate a broad readership, an introductory article by Akbari et al.1 is included covering the progress of androgenetics over 60 years and providing a glossary of the core terminology in medical genetics. Since the discovery that the Klinefelter syndrome phenotype is linked to 47, XXY karyotype, cytogenetic analysis has been successfully introduced to the male infertility workup, explaining 3%–4% of cases2 and adding value in clinical practice for patient counseling and management (e.g. original study by Zohdy et al. in this issue3). Access to whole-exome sequencing (WES) during the past 5–10 years has revealed the diverse landscape of monogenic infertility with over 600 proposed candidate genes.4 A thorough review by Riera-Escamilla and Nagirnaja5 including 19 WES-based studies in cohorts of unrelated cases with primary spermatogenic defects demonstrates the variability in detection rates of disease-causing variants across subphenotypes and different research settings. Across the studies, clinically relevant monogenic findings already explain 10%–20% cases of azoo/oligozoospermia and more than half of cases with 46, XY differences/disorders of sex development (DSD) or qualitative sperm defects.5-8 It is likely that the forthcoming years will bring along a further increase in the diagnostic yield of genetic infertility due to rapidly dropping costs of whole-genome sequencing (WGS). The richer information content of WGS compared with WES allows for reliable detection of genomic structural variants, as demonstrated in the original study by Khan et al.9 analyzing family cases from Pakistan. Due to high genetic and phenotypic heterogeneity, confirmation of novel gene–disease links has been a challenge. A large fraction of proposed gene–disease relationships has been reported in singleton cases or among the members of consanguineous families. To establish solid genotype-phenotype links, each finding must be confirmed in independent case(s), and their relevance to the routine clinical practice needs critical assessment. Stallmeyer et al.6 have undertaken an important task to evaluate the clinical validity of 313 candidate genes for diverse male infertility subtypes. In applying the standardized international evaluation criteria, only 70 genes with at least moderate evidence to contribute to the condition were reported. This is one step closer to routine utility of WES-based, advanced genetic testing offered by andrology clinics and infertility centers worldwide. An original study by Oud et al.10 represents another crucial contribution toward this goal, showing WES as a reliable first-tier method to simultaneously detect most common currently known genetic causes of male infertility—diverse monogenic conditions (including CFTR mutations), chromosomal abnormalities and AZF microdeletions. The diagnostic yield of this extended WES analysis already reached 23% in the clinical setting. The clinical validity of tested genes and standardized assessment of variant pathogenicity is not only important for molecular diagnostics, but also for patient management decisions. A comprehensive review by Idris et al.7 covers 46, XY DSD cases published from 2018 to 2023, highlighting broad the phenotypic variability and diverse genetics behind these conditions. The authors emphasize the essential import","journal":"Andrology","year":2025,"id":568878,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9646,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":254969,"name":"Kenneth I. Aston","orcid":"0000-0001-6459-2103","position":1,"is_corresponding":false},{"id":18863,"name":"Donald F. Conrad","orcid":"0000-0003-3828-8970","position":2,"is_corresponding":false},{"id":849904,"name":"Maris Laan","orcid":"0000-0002-8519-243X","position":0,"is_corresponding":true}],"reference_count":20,"raw_metadata":null,"created_at":"2026-07-19T02:56:55.795846Z","pmid":"40545437","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}