{
  "abstract": "Objectives Despite the clinical significance of neuropsychiatric systemic lupus erythematosus (NPSLE), which is a severe complication of SLE, clinical and genetic studies on NPSLE remain limited. This study aimed to identify the clinical features of NPSLE and explore genetic factors associated with NPSLE in a prospective lupus cohort.Methods The clinical features, disease activity and organ damage of 1205 Korean patients with SLE were assessed at least annually, and genome-wide genotyping with imputation was performed. The clinical and genetic associations of NPSLE, excluding minor events, and its specific subsets (seizure or psychosis) compared with those of non-NPSLE were analysed using genome-wide association studies (GWASs). The biological relevance of the identified loci was investigated through functional analyses.Results A total of 271 patients with NPSLE exhibited more clinically diverse manifestations (p=2.40×10 −4), especially in patients with seizure (N=84, p=4.86×10−14) and psychosis (N=26, p=8.29×10−5), compared with 934 patients with non-NPSLE. Notably, NPSLE patients significantly had greater organ damage (total Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) score: OR 1.49, p=3.28×10−17; non-NP SDI score: OR 1.22, p=7.61×10−5) than patients with non-NPSLE, adjusting for age, sex, hypertension, disease duration and antiphospholipid antibodies. GWAS revealed nine NPSLE-associated loci at a suggestive significance level (p<5×10⁻⁶). The nine nearest mapped genes were exclusively expressed in the brain (adjusted p=5.28×10−4), particularly in the basal ganglia, cortex and hippocampus (adjusted p<0.05).Conclusions Neuropsychiatric involvement in SLE increases clinical manifestations and extends organ damage beyond the nervous system, with NPSLE-related genetic variants highlighting their potential functional roles in various brain regions.",
  "authors": [
    {
      "affiliations": [
        "Rheumatology Research, Hanyang University Institute for Rheumatology Research, Seoul, Korea (the Republic of)",
        "Hanyang Institute of Bioscience and Biotechnology, Seoul, Korea (the Republic of)"
      ],
      "name": "Soojin Cha"
    },
    {
      "affiliations": [
        "Rheumatology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea (the Republic of)"
      ],
      "name": "Ga Young Ahn"
    },
    {
      "affiliations": [
        "Department of Biology, Kyung Hee University, Seoul, Korea (the Republic of)",
        "Department of Biomedical and Pharmaceutical Sciences, Kyung Hee University, Seoul, Korea (the Republic of)"
      ],
      "name": "Kwangwoo Kim"
    },
    {
      "affiliations": [
        "Rheumatology Research, Hanyang University Institute for Rheumatology Research, Seoul, Korea (the Republic of)",
        "Hanyang Institute of Bioscience and Biotechnology, Seoul, Korea (the Republic of)",
        "Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (the Republic of)"
      ],
      "name": "Hye-Soon Lee"
    },
    {
      "affiliations": [
        "Rheumatology Research, Hanyang University Institute for Rheumatology Research, Seoul, Korea (the Republic of)",
        "Hanyang Institute of Bioscience and Biotechnology, Seoul, Korea (the Republic of)",
        "Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (the Republic of)"
      ],
      "name": "Sang-Cheol Bae"
    },
    {
      "affiliations": [
        "Rheumatology Research, Hanyang University Institute for Rheumatology Research, Seoul, Korea (the Republic of)",
        "Hanyang Institute of Bioscience and Biotechnology, Seoul, Korea (the Republic of)",
        "Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea (the Republic of)"
      ],
      "name": "So-Young Bang"
    }
  ],
  "title": "Unveiling the clinical and genetic impact of neuropsychiatric involvement in systemic lupus erythematosus",
  "uid": "0ba685c2-918f-51a0-bae9-6842e4982dd3"
}