改善偏头痛首发患者的多基因风险预测。

IF 7.3 1区医学 Q1 CLINICAL NEUROLOGY

Journal of Headache and Pain Pub Date : 2024-09-27 DOI:10.1186/s10194-024-01870-8

Dora Torok, Peter Petschner, Daniel Baksa, Gabriella Juhasz

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引用次数: 0

摘要

背景：最近的荟萃分析估计偏头痛的SNP遗传率分别为14.6%和11.2%，而双生子的遗传率估计为30%-60%。本研究旨在调查 "偏头痛第一人"（G43（有先兆或无先兆偏头痛）是其一生中首次被诊断为偏头痛的患者）的遗传率：利用英国生物库（N = 199929）的数据，对6139名偏头痛首发患者和193790名健康对照者进行了全基因组关联研究（GWAS）。使用 SumHer 估算了基于 SNP 的遗传率，所有 SNP 的遗传率为 19.37% (± 0.019)，HapMap3 变异的遗传率为 21.31% (± 0.019)，大大超过了之前的估计值。关键风险位点包括 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：研究结果强调，在发病时排除合并症可提高遗传率估计和遗传信号检测，从而显著降低偏头痛的 "遗传率缺失 "程度。

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Improved polygenic risk prediction in migraine-first patients.

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.

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来源期刊

Journal of Headache and Pain 医学-临床神经学

CiteScore

11.80

自引率

13.50%

发文量

143

审稿时长

6-12 weeks

期刊介绍： The Journal of Headache and Pain, a peer-reviewed open-access journal published under the BMC brand, a part of Springer Nature, is dedicated to researchers engaged in all facets of headache and related pain syndromes. It encompasses epidemiology, public health, basic science, translational medicine, clinical trials, and real-world data. With a multidisciplinary approach, The Journal of Headache and Pain addresses headache medicine and related pain syndromes across all medical disciplines. It particularly encourages submissions in clinical, translational, and basic science fields, focusing on pain management, genetics, neurology, and internal medicine. The journal publishes research articles, reviews, letters to the Editor, as well as consensus articles and guidelines, aimed at promoting best practices in managing patients with headaches and related pain.