Large trans-ethnic meta-analysis identifies AKR1C4 as a novel gene associated with age at menarche.

摘要: STUDY QUESTION Does the expansion of genome-wide association studies (GWAS) to a broader range ancestries improve ability identify and generalise variants associated with age at menarche (AAM) in European populations wider world populations? SUMMARY ANSWER By including women diverse predominantly non-European ancestry large-scale meta-analysis AAM half being African ancestry, we identified new locus African-ancestry participants, generalised loci from GWAS individuals. WHAT IS KNOWN ALREADY is highly polygenic puberty trait various diseases later life. Both timing vary by race or ethnicity. The majority have been performed women. DESIGN, SIZE, DURATION We analysed total 38 546 who did not backgrounds: 25 149 seven ReproGen Consortium 13 397 UK Biobank. In addition, used an independent sample 5148 Southern Community Cohort Study (SCCS) for replication. PARTICIPANTS/MATERIALS, SETTING, METHODS Each was study ethnic group using linear regression models adjusted birth year study-specific covariates. Biobank results were meta-analysed inverse variance-weighted average method. A trans-ethnic also carried out assess heterogeneity due different ancestry. MAIN RESULTS AND THE ROLE OF CHANCE observed consistent direction effect sizes between our largest conducted Asian validated four (1p31, 6q16, 6q22 9q31) common genetic P  18 years) excluded analysis. Women may fully recall their as most many years later. Further are needed confirm extend these findings, but availability such replication samples limited. WIDER IMPLICATIONS FINDINGS Expanding ethnicities identification complex traits generalisation European-ancestry populations. FUNDING/COMPETING INTEREST(S) Funding provided CHARGE grant R01HL105756-07: Gene Discovery For CVD Aging Phenotypes NIH U24AG051129 awarded National Institute on (NIA). authors no conflict interest declare.