{"doi":"10.1136/bmjdrc-2019-001091","title":"Association of <i>G6PD</i> variants with hemoglobin A1c and impact on diabetes diagnosis in East Asian individuals","abstract":"Objective Hemoglobin A1c (HbA1c) accuracy is important for diabetes diagnosis and estimation of overall glycemia. The G6PD- Asahi variant which causes glucose-6-phosphate dehydrogenase (G6PD) deficiency has been shown to lower HbA1c independently of glycemia in African ancestry populations. As different G6PD variants occur in Asian ancestry, we sought to identify Asian-specific G6PD variants associated with HbA1c. Research design and methods In eight Asian population-based cohorts, we performed imputation on the X chromosome using the 1000 Genomes reference panel and tested for association with HbA1c (10 005 East Asians and 2051 South Asians). Results were meta-analyzed across studies. We compared the proportion of individuals classified as having diabetes/pre-diabetes by fasting glucose ≥100 mg/dL or HbA1c ≥5.7% units among carriers and non-carriers of HbA1c-associated variants. Results The strongest association was a missense variant ( G6PD -Canton, rs72554665, minor allele frequency=2.2%, effect in men=−0.76% unit, 95% CI −0.88 to −0.64, p=1.25×10 −27 , n=2844). Conditional analyses identified a secondary distinct signal, missense variant ( G6PD -Kaiping, rs72554664, minor allele frequency=1.6%, effect in men=−1.12 % unit, 95% CI −1.32 to −0.92, p=3.12×10 −15 , p conditional_Canton =7.57×10 −11 ). Adjusting for glucose did not attenuate their effects. The proportion of individuals with fasting glucose ≥100 mg/dL did not differ by carrier status of G6PD -Canton (p=0.21). Whereas the proportion of individuals with HbA1c ≥5.7% units was lower in carriers (5%) compared with non-carriers of G6PD -Canton (30%, p=0.03). Conclusions We identified two G6PD variants in East Asian men associated with non-glycemic lowering of HbA1c. Carriers of these variants are more likely to be underdiagnosed for diabetes or pre-diabetes than non-carriers if screened by HbA1c without confirmation by direct glucose measurements.","journal":"BMJ Open Diabetes Research & Care","year":2020,"id":77259,"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":19,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":402453,"name":"Victor Lim","orcid":"0000-0003-3051-4857","position":1,"is_corresponding":false},{"id":402454,"name":"Chaolong Wang","orcid":"0000-0003-3945-1012","position":2,"is_corresponding":false},{"id":402455,"name":"Jin Fang Chai","orcid":"0000-0003-3770-1137","position":3,"is_corresponding":false},{"id":390744,"name":"Rajkumar Dorajoo","orcid":"0000-0001-6608-2051","position":4,"is_corresponding":false},{"id":236703,"name":"Chew‐Kiat Heng","orcid":"0000-0002-7309-9473","position":5,"is_corresponding":false},{"id":260010,"name":"Rob M. van Dam","orcid":"0000-0002-7354-8734","position":6,"is_corresponding":false},{"id":260003,"name":"Woon‐Puay Koh","orcid":"0000-0002-5674-6341","position":7,"is_corresponding":false},{"id":341681,"name":"Jian‐Min Yuan","orcid":"0000-0002-4620-3108","position":8,"is_corresponding":false},{"id":22574,"name":"Jost B. Jonas","orcid":"0000-0003-2972-5227","position":9,"is_corresponding":false},{"id":402456,"name":"Ya Xing Wang","orcid":"0000-0003-2749-7793","position":10,"is_corresponding":false},{"id":402457,"name":"Wenbin Wei","orcid":"0000-0003-2386-0989","position":11,"is_corresponding":false},{"id":20712,"name":"Jianjun Liu","orcid":"0000-0002-3255-3019","position":12,"is_corresponding":false},{"id":402458,"name":"Dermot F. Reilly","orcid":"0000-0002-9456-1364","position":13,"is_corresponding":false},{"id":39319,"name":"Tien Yin Wong","orcid":"0000-0002-8448-1264","position":14,"is_corresponding":false},{"id":39406,"name":"Ching‐Yu Cheng","orcid":"0000-0003-0655-885X","position":15,"is_corresponding":false},{"id":240625,"name":"Xueling Sim","orcid":"0000-0002-1233-7642","position":16,"is_corresponding":false},{"id":263594,"name":"Aaron Leong","orcid":"0000-0002-3248-9547","position":0,"is_corresponding":true}],"reference_count":35,"raw_metadata":null,"created_at":"2026-07-18T21:48:50.085103Z","pmid":"32209585","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":[]}