{
    "abstract": "The genetic factors of stroke in South Asians are largely unexplored. Exome-wide sequencing and association analysis (ExWAS) in 75\u2009K Pakistanis identified NM_000435.3(NOTCH3):c.3691\u2009C\u2009>\u2009T, encoding the missense amino acid substitution p.Arg1231Cys, enriched in South Asians (alternate allele frequency = 0.58% compared to 0.019% in Western Europeans), and associated with subcortical hemorrhagic stroke [odds ratio (OR)\u2009=\u20093.39, 95% confidence interval (CI)\u2009=\u2009[2.26, 5.10], p\u2009=\u20093.87\u2009\u00d7\u200910",
    "authors": [
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Juan Lorenzo",
            "initials": "JL",
            "lastname": "Rodriguez-Flores"
        },
        {
            "affiliation": "Columbia University, New York, NY, USA.\nCenter for Non-Communicable Diseases, Karachi, Pakistan.",
            "firstname": "Shareef",
            "initials": "S",
            "lastname": "Khalid"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Neelroop",
            "initials": "N",
            "lastname": "Parikshak"
        },
        {
            "affiliation": "Center for Non-Communicable Diseases, Karachi, Pakistan.",
            "firstname": "Asif",
            "initials": "A",
            "lastname": "Rasheed"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Bin",
            "initials": "B",
            "lastname": "Ye"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Manav",
            "initials": "M",
            "lastname": "Kapoor"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Joshua",
            "initials": "J",
            "lastname": "Backman"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Farshid",
            "initials": "F",
            "lastname": "Sepehrband"
        },
        {
            "affiliation": "Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.",
            "firstname": "Silvio Alessandro Di",
            "initials": "SAD",
            "lastname": "Gioia"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Sahar",
            "initials": "S",
            "lastname": "Gelfman"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Tanima",
            "initials": "T",
            "lastname": "De"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Nilanjana",
            "initials": "N",
            "lastname": "Banerjee"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Deepika",
            "initials": "D",
            "lastname": "Sharma"
        },
        {
            "affiliation": "Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.",
            "firstname": "Hector",
            "initials": "H",
            "lastname": "Martinez"
        },
        {
            "affiliation": "Rye Country Day School, Rye, NY, USA.",
            "firstname": "Sofia",
            "initials": "S",
            "lastname": "Castaneda"
        },
        {
            "affiliation": "Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.",
            "firstname": "David",
            "initials": "D",
            "lastname": "D'Ambrosio"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Xingmin A",
            "initials": "XA",
            "lastname": "Zhang"
        },
        {
            "affiliation": "Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.",
            "firstname": "Pengcheng",
            "initials": "P",
            "lastname": "Xun"
        },
        {
            "affiliation": "University of California at Los Angeles, Los Angeles, CA, USA.",
            "firstname": "Ellen",
            "initials": "E",
            "lastname": "Tsai"
        },
        {
            "affiliation": "Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.",
            "firstname": "I-Chun",
            "initials": "IC",
            "lastname": "Tsai"
        },
        {
            "affiliation": null,
            "firstname": null,
            "initials": null,
            "lastname": null
        },
        {
            "affiliation": "Center for Non-Communicable Diseases, Karachi, Pakistan.",
            "firstname": "Maleeha Zaman",
            "initials": "MZ",
            "lastname": "Khan"
        },
        {
            "affiliation": "Center for Non-Communicable Diseases, Karachi, Pakistan.",
            "firstname": "Muhammad",
            "initials": "M",
            "lastname": "Jahanzaib"
        },
        {
            "affiliation": "Center for Non-Communicable Diseases, Karachi, Pakistan.",
            "firstname": "Muhammad Rehan",
            "initials": "MR",
            "lastname": "Mian"
        },
        {
            "affiliation": "Center for Non-Communicable Diseases, Karachi, Pakistan.",
            "firstname": "Muhammad Bilal",
            "initials": "MB",
            "lastname": "Liaqat"
        },
        {
            "affiliation": "Dow University of Health Sciences and Civil Hospital, Karachi, Pakistan.",
            "firstname": "Khalid",
            "initials": "K",
            "lastname": "Mahmood"
        },
        {
            "affiliation": "Lahore General Hospital, Lahore, Pakistan.",
            "firstname": "Tanvir Us",
            "initials": "TU",
            "lastname": "Salam"
        },
        {
            "affiliation": "Lahore General Hospital, Lahore, Pakistan.",
            "firstname": "Muhammad",
            "initials": "M",
            "lastname": "Hussain"
        },
        {
            "affiliation": "Department of Neurology, Allied Hospital, Faisalabad, Pakistan.",
            "firstname": "Javed",
            "initials": "J",
            "lastname": "Iqbal"
        },
        {
            "affiliation": "Department of Neurology, Aziz Fatima Hospital, Faisalabad, Pakistan.",
            "firstname": "Faizan",
            "initials": "F",
            "lastname": "Aslam"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Michael N",
            "initials": "MN",
            "lastname": "Cantor"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Gannie",
            "initials": "G",
            "lastname": "Tzoneva"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "John",
            "initials": "J",
            "lastname": "Overton"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Jonathan",
            "initials": "J",
            "lastname": "Marchini"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Jeffrey G",
            "initials": "JG",
            "lastname": "Reid"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Aris",
            "initials": "A",
            "lastname": "Baras"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Niek",
            "initials": "N",
            "lastname": "Verweij"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Luca A",
            "initials": "LA",
            "lastname": "Lotta"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Giovanni",
            "initials": "G",
            "lastname": "Coppola"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Katia",
            "initials": "K",
            "lastname": "Karalis"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Aris",
            "initials": "A",
            "lastname": "Economides"
        },
        {
            "affiliation": "Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.",
            "firstname": "Sergio",
            "initials": "S",
            "lastname": "Fazio"
        },
        {
            "affiliation": "Regeneron Pharmaceuticals Inc, Tarrytown, NY, USA.",
            "firstname": "Wolfgang",
            "initials": "W",
            "lastname": "Liedtke"
        },
        {
            "affiliation": "Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.",
            "firstname": "John",
            "initials": "J",
            "lastname": "Danesh"
        },
        {
            "affiliation": "Section of Neurology, Department of Medicine, Aga Khan University, Karachi, Pakistan.",
            "firstname": "Ayeesha",
            "initials": "A",
            "lastname": "Kamal"
        },
        {
            "affiliation": "Center for Non-Communicable Diseases, Karachi, Pakistan.",
            "firstname": "Philippe",
            "initials": "P",
            "lastname": "Frossard"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA.",
            "firstname": "Thomas",
            "initials": "T",
            "lastname": "Coleman"
        },
        {
            "affiliation": "Regeneron Genetics Center, Tarrytown, NY, USA. alan.shuldiner@regeneron.com.",
            "firstname": "Alan R",
            "initials": "AR",
            "lastname": "Shuldiner"
        },
        {
            "affiliation": "Columbia University, New York, NY, USA. danish.saleheen@cncdpk.com.\nCenter for Non-Communicable Diseases, Karachi, Pakistan. danish.saleheen@cncdpk.com.",
            "firstname": "Danish",
            "initials": "D",
            "lastname": "Saleheen"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 2024. The Author(s).",
    "doi": "10.1038/s41467-024-51819-3\n10.1038/s41588-020-0580-y\n10.1016/S1474-4422(21)00252-0\n10.12669/pjms.36.7.2824\n10.1159/000519554\n10.1111/j.1747-4949.2009.00327.x\n10.1161/JAHA.123.031303\n10.1016/S1474-4422(09)70127-9\n10.1161/STROKEAHA.117.018859\n10.1038/s41586-022-05165-3\n10.1038/ng.3592\n10.1016/j.pbiomolbio.2007.07.006\n10.1093/nar/gkab225\n10.1212/WNL.0000000000010525\n10.1038/s41525-021-00270-0\n10.1038/ng.3715\n10.1093/brain/awac486\n10.1001/jamaneurol.2022.3832\n10.1038/s41436-018-0088-3\n10.1002/acn3.344\n10.1093/brain/aww011\n10.1093/hmg/ddz285\n10.1002/ana.25284\n10.1161/ATVBAHA.108.171751\n10.1038/s41588-021-00870-7\n10.1038/s41586-021-04103-z\n10.1111/j.2517-6161.1995.tb02031.x\n10.1038/s41586-018-0571-7\n10.1016/j.neuroimage.2016.07.018\n10.1161/01.STR.24.1.35\n10.1016/0140-6736(91)93206-O\n10.1038/nature22034\n10.3389/fgene.2021.673167\n10.1038/s41586-020-2308-7\n10.1038/nature15393\n10.1101/gr.4565806\n10.1093/nar/gks539\n10.1101/gr.092619.109\n10.1093/nar/gkab266\n10.1186/s13073-020-00803-9\n10.1038/ng1706\n10.1038/ng1847\n10.1186/s13742-015-0047-8\n10.1172/JCI39733",
    "journal": "Nature communications",
    "keywords": [],
    "methods": null,
    "publication_date": "2024-09-14",
    "pubmed_id": "39271666\n32139905\n34487721\n33235553\n28431835\n34695824\n19765127\n38108258\n19539236\n29674522\n36180795\n27428751\n17854869\n33849055\n32732295\n35046417\n27841878\n36535904\n36300346\n30032161\n24234437\n27844030\n26912635\n31960911\n30014602\n18818417\n34017140\n34662886\n30305740\n27402600\n7678184\n1675378\n28406212\n34108994\n32461654\n26432245\n16902084\n22689647\n23315928\n19602639\n33893808\n33261662\n16415888\n16862161\n30531897\n25722852\n20071773",
    "results": null,
    "title": "NOTCH3 p.Arg1231Cys is markedly enriched in South Asians and associated with stroke.",
    "xml": "<Element 'PubmedArticle' at 0x78850414ec00>"
}