Identifying causal genes for migraine by integrating the proteome and transcriptome.
J Headache Pain
; 24(1): 111, 2023 Aug 17.
Article
en En
| MEDLINE
| ID: mdl-37592229
ABSTRACT
BACKGROUND:
While previous genome-wide association studies (GWAS) have identified multiple risk variants for migraine, there is a lack of evidence about how these variants contribute to the development of migraine. We employed an integrative pipeline to efficiently transform genetic associations to identify causal genes for migraine.METHODS:
We conducted a proteome-wide association study (PWAS) by combining data from the migraine GWAS data with proteomic data from the human brain and plasma to identify proteins that may play a role in the risk of developing migraine. We also combined data from GWAS of migraine with a novel joint-tissue imputation (JTI) prediction model of 17 migraine-related human tissues to conduct transcriptome-wide association studies (TWAS) together with the fine mapping method FOCUS to identify disease-associated genes.RESULTS:
We identified 13 genes in the human brain and plasma proteome that modulate migraine risk by regulating protein abundance. In addition, 62 associated genes not reported in previous migraine TWAS studies were identified by our analysis of migraine using TWAS and fine mapping. Five genes including ICA1L, TREX1, STAT6, UFL1, and B3GNT8 showed significant associations with migraine at both the proteome and transcriptome, these genes are mainly expressed in ependymal cells, neurons, and glial cells, and are potential target genes for prevention of neuronal signaling and inflammatory responses in the pathogenesis of migraine.CONCLUSIONS:
Our proteomic and transcriptome findings have identified disease-associated genes that may give new insights into the pathogenesis and potential therapeutic targets for migraine.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Proteoma
/
Trastornos Migrañosos
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
J Headache Pain
Asunto de la revista:
MEDICINA INTERNA
/
NEUROLOGIA
/
PSICOFISIOLOGIA
Año:
2023
Tipo del documento:
Article
País de afiliación:
China