Falcone Guido J, Wolfe Stacey Q, Zedde Marialuisa, Pascarella Rosario, Jimenez-Conde Jordi, Vallverdu Prats Marta, Jimenez-Balado Joan, Pezzini Alessandro, Rossi Sandra, Al-Shahi Salman Rustam, Samarasekera Neshika, Zand Ramin, Li Jinag, Jern Christina, Strbian Daniel, Tomppo Liisa, Sallinen Hanne, Hernandez Guillamon Mar, Selim Magdy, Owolabi Mayowa, Akinyemi Rufus, Fakunle Gregory, Lee Tsong-Hai, Werring David, Hostettler Isabel C, Houlden Henry, Sharma Pankaj, John Isaac, Ken-Dror Gie, Jenkins Wendy, Sheth Kevin N, Sansing Lauren H, Sanghera Dharambir K, Sidorov Evgeny, Fernandez-Cadenas Israel, Cárcel-Márquez Jara, Chen Ching-Jen, Becerril-Gaitan Andrea, Lee Keon-Joo, Bae Hee-Joon, Dichgans Martin, Malik Rainer, Debette Stephanie, Mishra Aniket, Pare Guillaume, Chong Michael, Kamatani Yoichiro, Chen Zhengming, Walters Robin G, Seshadri Sudha, Fornage Myriam, Sudlow Catherine, Gilkerson Lee A, Khandwala Vivek J, Maloney Thomas C, Demel Stacie, Parodi Livia, Zand Ramin, Nyquist Paul, Ziai Wendy, Worrall Bradford, Achala Vagal M, Langefeld Carl D, Rosand Jonathan, Anderson Christopher D, Woo Daniel
medRxiv. 2025 Jun 13:2025.06.11.25329301. doi: 10.1101/2025.06.11.25329301.
Spontaneous, non-traumatic intracranial hemorrhage (ICH) is highly heritable disease. However, the identification of the genetic risk factors driving this high genetic predisposition has been limited by small sample sizes and underrepresentation of non-European populations. The ERICH-GENE study will gather and harmonize clinical, neuroimaging and genomic data on the largest and more diverse collection of ICH cases assembled to date.
ERICH-GENE is an NIH-funded, multi-center, international, genetic and neuroimaging study that aims to achieve the necessary sample size and diversity required to accurately describe the genetic architecture and trans-ethnic variation of ICH. ERICH-GENE will collect and harmonize clinical, neuroimaging and genomic data at least 10,000 multi-ethnic ICH cases. These data will be aggregated with 20,000 existing ICH cases and 600,000 ICH-free controls available through completed studies by the International Stroke Genetics Consortium. To ensure validity, data will undergo extensive harmonization, including expert review of neuroimages to ensure spontaneous etiology and hemorrhage location. We will conduct genome-wide association studies of risk, severity and outcome of ICH, testing for effect modification by race/ethnicity, sex and hemorrhage location. We will also conduct pathway, polygenic risk score and Mendelian randomization analyses.
This study will include whole genome sequencing data from 10,850 spontaneous ICH samples, including clinical and radiographic phenotypic data to ensure reliability of true non-traumatic, non-lesional ICH and lobar vs nonlobar location. Of these, 1,497 have already been genotyped using genome-wide arrays, 3,753 have undergone whole genome sequencing, and 5,600 will undergo genome-wide genotyping through ERICH-GENE. There are currently 42 contributing sites exceeding study milestone enrollments. 16,175 radiographic studies from 4,974 patients have been uploaded for harmonization to date, including 26% lobar and 64% nonlobar hemorrhages. Neuroimaging assessment will also include grading for white matter hyperintensities, cerebral atrophy, and presence and severity of IVH. Nearly 6,000 ICH cases will complete genotyping by August 2025. Data/material transfer agreements for summary statistics as well as additional samples are on target to meet the study's objectives.
ERICH-GENE is the largest trans-ethnic genetic study of ICH conducted to date. Combining a diverse patient population with expert adjudication of neuroimaging data, ERICH-GENE will identify genetic risk loci that drive the high heritability observed for this disease and make a significant contribution to the understanding of the trans-ethnic variation of its genetic architecture.
自发性非创伤性颅内出血（ICH）是一种高度可遗传的疾病。然而，由于样本量小以及非欧洲人群代表性不足，驱动这种高遗传易感性的遗传风险因素的识别受到了限制。ERICH-GENE研究将收集并整合迄今为止最大且最多样化的ICH病例集合的临床、神经影像学和基因组数据。
ERICH-GENE是一项由美国国立卫生研究院资助的多中心国际遗传与神经影像学研究，旨在获得准确描述ICH的遗传结构和跨种族变异所需的必要样本量和多样性。ERICH-GENE将收集并整合至少10000例多民族ICH病例的临床、神经影像学和基因组数据。这些数据将与国际卒中遗传学联盟通过已完成的研究提供的20000例现有ICH病例和600000例无ICH对照进行汇总。为确保有效性，数据将进行广泛的整合，包括由专家对神经影像进行审查，以确保自发性病因和出血部位。我们将对ICH的风险、严重程度和结局进行全基因组关联研究，检测种族/民族、性别和出血部位的效应修饰。我们还将进行通路分析、多基因风险评分分析和孟德尔随机化分析。
本研究将包括来自10850份自发性ICH样本的全基因组测序数据，包括临床和影像学表型数据，以确保真正的非创伤性、非病变性ICH以及叶状与非叶状部位的可靠性。其中，1497份样本已使用全基因组阵列进行基因分型，3753份样本已进行全基因组测序，5600份样本将通过ERICH-GENE进行全基因组基因分型。目前有42个参与站点超过了研究里程碑的入组人数。截至目前，已上传了来自4974名患者的16175份影像学研究进行整合，其中叶状出血占26%，非叶状出血占64%。神经影像学评估还将包括对白质高信号、脑萎缩以及IVH的存在和严重程度进行分级。到2025年8月，将近6000例ICH病例将完成基因分型。汇总统计数据以及额外样本的数据/材料转移协议有望实现研究目标。
ERICH-GENE是迄今为止开展的最大规模的ICH跨种族遗传研究。将多样化的患者群体与神经影像学数据的专家判定相结合，ERICH-GENE将识别出驱动该疾病高遗传性的遗传风险位点，并为理解其遗传结构的跨种族变异做出重大贡献。
