偏头痛首发患者的多基因风险预测得到改善。

Improved polygenic risk prediction in migraine-first patients.

机构信息

Department of Pharmacodynamics, Faculty of Pharmaceutical Sciences, Semmelweis University, Nagyvarad ter 4., Budapest, 1096, Hungary.

NAP3.0-SE Neuropsychopharmacology Research Group, Hungarian Brain Research Program, Semmelweis University, Budapest, Hungary.

出版信息

J Headache Pain. 2024 Sep 27;25(1):161. doi: 10.1186/s10194-024-01870-8.

DOI:10.1186/s10194-024-01870-8

PMID:39333847

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11438044/

Abstract

BACKGROUND

Recent meta-analyses estimated 14.6% and 11.2% SNP-based heritability of migraine, compared to twin-heritability estimates of 30-60%. This study aimed to investigate heritability estimates in "migraine-first" individuals, patients for whom G43 (migraine with or without aura) was their first medical diagnosis in their lifetime.

FINDINGS

Using data from the UK Biobank (N = 199,929), genome-wide association studies (GWAS) were conducted on 6,139 migraine-first patients and 193,790 healthy controls. SNP-based heritability was estimated using SumHer, yielding 19.37% (± 0.019) for all SNPs and 21.31% (± 0.019) for HapMap3 variants, substantially surpassing previous estimates. Key risk loci included PRDM16, FHL5, ASTN2, STAT6/LRP1, and SLC24A3, and pathway analyses highlighted retinol metabolism and steroid hormone biosynthesis as important pathways in these patients.

CONCLUSIONS

The findings underscore that excluding comorbidities at onset time can enhance heritability estimates and genetic signal detection, significantly reducing the extent of "missing heritability" in migraine.

摘要

背景

最近的荟萃分析估计，偏头痛的基于 SNP 的遗传率为 14.6%和 11.2%，而双胞胎遗传率估计为 30-60%。本研究旨在调查“偏头痛首发”个体的遗传率估计值，即对于这些患者，G43（有或无先兆的偏头痛）是他们一生中的首次医学诊断。

发现

本研究使用英国生物库（N=199929）的数据，对 6139 名偏头痛首发患者和 193790 名健康对照进行了全基因组关联研究（GWAS）。使用 SumHer 估算基于 SNP 的遗传率，得到所有 SNP 的遗传率为 19.37%（±0.019），HapMap3 变体的遗传率为 21.31%（±0.019），大大超过了先前的估计值。关键风险基因座包括 PRDM16、FHL5、ASTN2、STAT6/LRP1 和 SLC24A3，通路分析强调视黄醇代谢和类固醇激素生物合成是这些患者的重要通路。