Genome-wide association study of primary dysmenorrhea in the Taiwan Biobank validates associations near the NGF and IL1 gene loci.
J Hum Genet
; 67(8): 449-458, 2022 Aug.
Article
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| MEDLINE
| ID: mdl-35351958
ABSTRACT
Using the Taiwan Biobank, we aimed to identify traits and genetic variations that could predispose Han Chinese women to primary dysmenorrhea. Cases of primary dysmenorrhea included those who self-reported "frequent dysmenorrhea" in a dysmenorrhea-related Taiwan Biobank questionnaire, and those who have been diagnosed with severe dysmenorrhea by a physician. Controls were those without self-reported dysmenorrhea. Customized Axiom-Taiwan Biobank Array Plates were used to perform whole-genome genotyping, PLINK was used to perform association tests, and HaploReg was used to conduct functional annotations of SNPs and bioinformatic analyses. The GWAS analysis included 1186 cases and 24,020 controls. We identified 53 SNPs that achieved genome-wide significance (P < 5 × 10-8, which clustered in 2 regions. The first SNP cluster was on chromosome 1, and included 24 high LD (R2 > 0.88) variants around the NGF gene (lowest P value of 3.83 × 10-13 for rs2982742). Most SNPs occurred within NGF introns, and were predicted to alter regulatory binding motifs. The second SNP cluster was on chromosome 2, including 7 high LD (R2 > 0.94) variants around the IL1A and IL1B loci (lowest P value of 7.43 × 10-10 for rs11676014) and 22 SNPs that did not reach significance after conditional analysis. Most of these SNPs resided within IL1A and IL1B introns, while 2 SNPs may be in the promoter histone marks or promoter flanking regions of IL1B. To conclude, data from this study suggest that NGF, IL1A, and IL1B may be involved in the pathogenesis of primary dysmenorrhea in the Han Chinese in Taiwan.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Factor de Crecimiento Nervioso
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Dismenorrea
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Interleucina-1alfa
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Interleucina-1beta
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Female
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Humans
País/Región como asunto:
Asia
Idioma:
En
Revista:
J Hum Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Taiwán