Dataset Information

A large electronic-health-record-based genome-wide study of serum lipids.

ABSTRACT: A genome-wide association study (GWAS) of 94,674 ancestrally diverse Kaiser Permanente members using 478,866 longitudinal electronic health record (EHR)-derived measurements for untreated serum lipid levels empowered multiple new findings: 121 new SNP associations (46 primary, 15 conditional, and 60 in meta-analysis with Global Lipids Genetic Consortium data); an increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater impact in females for LDL, HDL, and total cholesterol and the opposite for triglycerides); differences in variance explained among non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistatic interaction, with strong evidence for both at the ABO and FUT2 genes for LDL; and tissue-specific enrichment of GWAS-associated SNPs among liver, adipose, and pancreas eQTLs. Using EHR pharmacy data, both LDL and triglyceride genetic risk scores (477 SNPs) were strongly predictive of age at initiation of lipid-lowering treatment. These findings highlight the value of longitudinal EHRs for identifying new genetic features of cholesterol and lipoprotein metabolism with implications for lipid treatment and risk of coronary heart disease.

SUBMITTER: Hoffmann TJ

PROVIDER: S-EPMC5942247 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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A large electronic-health-record-based genome-wide study of serum lipids.

Hoffmann Thomas J TJ Theusch Elizabeth E Haldar Tanushree T Ranatunga Dilrini K DK Jorgenson Eric E Medina Marisa W MW Kvale Mark N MN Kwok Pui-Yan PY Schaefer Catherine C Krauss Ronald M RM Iribarren Carlos C Risch Neil N

Nature genetics 20180305 3

A genome-wide association study (GWAS) of 94,674 ancestrally diverse Kaiser Permanente members using 478,866 longitudinal electronic health record (EHR)-derived measurements for untreated serum lipid levels empowered multiple new findings: 121 new SNP associations (46 primary, 15 conditional, and 60 in meta-analysis with Global Lipids Genetic Consortium data); an increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater impact in females for ...[more]

PMID: 29507422

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Project description:BACKGROUND:The bidirectional encoder representations from transformers (BERT) model has achieved great success in many natural language processing (NLP) tasks, such as named entity recognition and question answering. However, little prior work has explored this model to be used for an important task in the biomedical and clinical domains, namely entity normalization. OBJECTIVE:We aim to investigate the effectiveness of BERT-based models for biomedical or clinical entity normalization. In addition, our second objective is to investigate whether the domains of training data influence the performances of BERT-based models as well as the degree of influence. METHODS:Our data was comprised of 1.5 million unlabeled electronic health record (EHR) notes. We first fine-tuned BioBERT on this large collection of unlabeled EHR notes. This generated our BERT-based model trained using 1.5 million electronic health record notes (EhrBERT). We then further fine-tuned EhrBERT, BioBERT, and BERT on three annotated corpora for biomedical and clinical entity normalization: the Medication, Indication, and Adverse Drug Events (MADE) 1.0 corpus, the National Center for Biotechnology Information (NCBI) disease corpus, and the Chemical-Disease Relations (CDR) corpus. We compared our models with two state-of-the-art normalization systems, namely MetaMap and disease name normalization (DNorm). RESULTS:EhrBERT achieved 40.95% F1 in the MADE 1.0 corpus for mapping named entities to the Medical Dictionary for Regulatory Activities and the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), which have about 380,000 terms. In this corpus, EhrBERT outperformed MetaMap by 2.36% in F1. For the NCBI disease corpus and CDR corpus, EhrBERT also outperformed DNorm by improving the F1 scores from 88.37% and 89.92% to 90.35% and 93.82%, respectively. Compared with BioBERT and BERT, EhrBERT outperformed them on the MADE 1.0 corpus and the CDR corpus. CONCLUSIONS:Our work shows that BERT-based models have achieved state-of-the-art performance for biomedical and clinical entity normalization. BERT-based models can be readily fine-tuned to normalize any kind of named entities.

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A large electronic-health-record-based genome-wide study of serum lipids.

Publications

A large electronic-health-record-based genome-wide study of serum lipids.

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