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• W4387496639 abstract "Borderline Personality Disorder (BPD) is a psychiatric illness characterized by marked instability in emotions, self-image, and interpersonal relationships. Although the lifetime prevalence of BPD in the general population is only 1–3%, individuals with BPD make up a large proportion of the patient population receiving treatment in psychiatric hospital services. To develop more effective treatment options and aid early intervention, we must improve our understanding of the etiology of BPD. Previous twin and family studies reported a broad-sense heritability of 60–75%. More recently, genome-wide association studies (GWAS) have shown that BPD has a polygenic basis and is genetically correlated with depression, schizophrenia, and bipolar disorder. To investigate how common genetic variation influences the likelihood of developing BPD, we will conduct a GWAS of BPD in the iPSYCH2015 sample accounting for age at diagnosis and family history. iPSYCH is a nationally representative case-cohort study of all individuals born in Denmark between 1981 and 2008 and diagnosed with a major psychiatric disorder (i.e., affective disorder, attention deficit hyperactivity disorder, schizophrenia spectrum disorder, autism spectrum disorder, or postpartum disorder) by 2015 and 50,615 individuals randomly selected from the population for the cohort. We will identify individuals diagnosed with BPD within the entire iPSYCH2015 sample using the Danish Psychiatric Central Research Register (ICD-10 code F60.3; N=7,113). All individuals will be followed up until diagnosis with BPD, emigration, death, or December 31st, 2018, whichever came first. Individuals from the iPSYCH2015 cohort without a diagnosis of BPD by the end of the follow-up period will be used as the cohort for this study. We will estimate the latent genetic liability for BPD for each individual with the extended liability threshold model conditioned on family history (LT-FH++) method. LT-FH++ is an alternative to traditional time-to-event analysis and can account for family history, right censoring, sex, and cohort effects. For our analysis, we will use the age at diagnosis, family history of BPD, and the cumulative incidence proportion of BPD stratified by birth year and sex of the entire Danish population from national register data. We will use the estimated genetic liability as a continuous phenotype to conduct a GWAS of BPD in BOLT-LMM. Ancestry principal components and genotyping array will be included as covariates. We plan to conduct further sensitivity analyses to investigate cross-trait genetic architectures, especially with other psychiatric disorders such as major depressive disorder, schizophrenia, and bipolar disorder, whilst accounting for the ascertainment method in iPSYCH based on these diagnoses. This study will be the first GWAS of BPD to use time-to-event information and family history to date, leveraging information from the Danish national registers to increase the power to detect genetic risk factors for BPD. The ascertainment of the cases in iPSYCH presents both a challenge and a unique opportunity to investigate cross-trait genetic architectures in the context of BPD." @default.
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• W4387496639 date "2023-10-01" @default.
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• W4387496639 title "T77. GENOME-WIDE ASSOCIATION STUDY OF BORDERLINE PERSONALITY DISORDER ACCOUNTING FOR AGE AT DIAGNOSIS AND FAMILY HISTORY IN IPSYCH" @default.
• W4387496639 doi "https://doi.org/10.1016/j.euroneuro.2023.08.361" @default.
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