Expanded carrier screening in a Southwestern Chinese population indicates East Asian specific low-frequency pathogenic variants account for nearly half of the at-risk couple rate.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος:	Expanded carrier screening in a Southwestern Chinese population indicates East Asian specific low-frequency pathogenic variants account for nearly half of the at-risk couple rate.
Συγγραφείς:	Liu S; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Cao L; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Zhang VW; AmCare Genomics Lab, Guangzhou, Guangdong, China., Huang S; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Liu H; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Wei X; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Luo Y; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Li Y; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Zhou L; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Jiang L; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Zhu Q; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China hongqian.liu@163.com zhuqian_2009@163.com.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China., Liu H; Department of Medical Genetics, Sichuan University West China Second University Hospital Department of Medical Genetics, Chengdu, Sichuan, China hongqian.liu@163.com zhuqian_2009@163.com.; Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, Sichuan, China.
Πηγή:	Journal of medical genetics [J Med Genet] 2026 Jun 25; Vol. 63 (7), pp. 447-455. Date of Electronic Publication: 2026 Jun 25.
Τύπος έκδοσης:	Journal Article
Γλώσσα:	English
Στοιχεία περιοδικού:	Publisher: British Medical Association Country of Publication: England NLM ID: 2985087R Publication Model: Electronic Cited Medium: Internet ISSN: 1468-6244 (Electronic) Linking ISSN: 00222593 NLM ISO Abbreviation: J Med Genet Subsets: MEDLINE
Imprint Name(s):	Original Publication: London : British Medical Association
Ιατρικοί όροι (MeSH):	Genetic Carrier Screening/methods , Asian People/genetics, Gene Frequency/genetics ; China/epidemiology ; Connexin 26/genetics ; Humans ; Male ; Female ; Heterozygote ; East Asian People ; Genetic Testing ; Alleles ; Genetic Predisposition to Disease ; Mutation
Περίληψη:	Background: The optimal disease spectrum for carrier screening (CS) remains debated. We aimed to characterise the carrier landscape and quantify the at-risk couple rate (ACR) components in a Chinese population to guide panel design. Methods: Using a 334-gene expanded CS panel, we screened 3748 individuals from Sichuan, China. Pathogenic/likely pathogenic (P/LP) variants were classified by allele frequency and geographic specificity. Results: Overall, 65.55% of participants carried at least one P/LP variant. We identified 83 at-risk couples (ACR 5.19%), including 55 couples at risk for autosomal recessive (AR) disorders. We catalogued 1372 P/LP variants for AR conditions. Notably, 46 variants were classified as low frequency (minor allele frequency ≥0.1%). Among these 46 low-frequency variants, 54% (25/46) were identified as East Asian-specific. Strikingly, these 25 East Asian-specific variants contributed 41.8% (23/55) to the AR at-risk couples, whereas 11 globally shared alleles contributed only 9.1%. Three regionally enriched variants in HBB, GJB2 and SLC25A13 alone contributed 20% to the AR ACR. Conclusion: East Asian-specific low-frequency variants significantly contribute to the carrier burden in this population, accounting for nearly half of the AR risk. These findings provide empirical evidence that CS panels should prioritise population-specific carrier frequencies over global data to maximise clinical utility in regions with specific ethnic compositions. (© Author(s) (or their employer(s)) 2026. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)
Competing Interests:	Competing interests: VWZ is an employee of AmCare Genomics Lab and does not hold any stocks or bonds.
Contributed Indexing:	Keywords: Gene Frequency; Genetic Carrier Screening; Genetic Load; Genetics, Population
Substance Nomenclature:	127120-53-0 (Connexin 26) 0 (GJB2 protein, human)
Entry Date(s):	Date Created: 20260403 Date Completed: 20260626 Latest Revision: 20260707
Update Code:	20260707
DOI:	10.1136/jmg-2025-111273
PMID:	41932824
Βάση Δεδομένων:	MEDLINE

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