Dataset Information

Genome-wide Association Study of Dimensional Psychopathology Using Electronic Health Records.

ABSTRACT: BACKGROUND:Genetic studies of neuropsychiatric disease strongly suggest an overlap in liability. There are growing efforts to characterize these diseases dimensionally rather than categorically, but the extent to which such dimensional models correspond to biology is unknown. METHODS:We applied a newly developed natural language processing method to extract five symptom dimensions based on the National Institute of Mental Health Research Domain Criteria definitions from narrative hospital discharge notes in a large biobank. We conducted a genome-wide association study to examine whether common variants were associated with each of these dimensions as quantitative traits. RESULTS:Among 4687 individuals, loci in three of five domains exceeded a genome-wide threshold for statistical significance. These included a locus spanning the neocortical development genes RFPL3 and RFPL3S for arousal (p = 2.29 × 10-8) and one spanning the FPR3 gene for cognition (p = 3.22 × 10-8). CONCLUSIONS:Natural language processing identifies dimensional phenotypes that may facilitate the discovery of common genetic variation that is relevant to psychopathology.

SUBMITTER: McCoy TH

PROVIDER: S-EPMC5972060 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Genome-wide Association Study of Dimensional Psychopathology Using Electronic Health Records.

McCoy Thomas H TH Castro Victor M VM Hart Kamber L KL Pellegrini Amelia M AM Yu Sheng S Cai Tianxi T Perlis Roy H RH

Biological psychiatry 20180226 12

<h4>Background</h4>Genetic studies of neuropsychiatric disease strongly suggest an overlap in liability. There are growing efforts to characterize these diseases dimensionally rather than categorically, but the extent to which such dimensional models correspond to biology is unknown.<h4>Methods</h4>We applied a newly developed natural language processing method to extract five symptom dimensions based on the National Institute of Mental Health Research Domain Criteria definitions from narrative ...[more]

PMID: 29496196

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Project description:Age-related hearing impairment (ARHI), one of the most common sensory disorders, can be mitigated, but not cured or eliminated. To identify genetic influences underlying ARHI, we conducted a genome-wide association study of ARHI in 6,527 cases and 45,882 controls among the non-Hispanic whites from the Genetic Epidemiology Research on Adult Health and Aging (GERA) cohort. We identified two novel genome-wide significant SNPs: rs4932196 (odds ratio = 1.185, p = 4.0x10-11), 52Kb 3' of ISG20, which replicated in a meta-analysis of the other GERA race/ethnicity groups (1,025 cases, 12,388 controls, p = 0.00094) and in a UK Biobank case-control analysis (30,802 self-reported cases, 78,586 controls, p = 0.015); and rs58389158 (odds ratio = 1.132, p = 1.8x10-9), which replicated in the UK Biobank (p = 0.00021). The latter SNP lies just outside exon 8 and is highly correlated (r2 = 0.96) with the missense SNP rs5756795 in exon 7 of TRIOBP, a gene previously associated with prelingual nonsyndromic hearing loss. We further tested these SNPs in phenotypes from audiologist notes available on a subset of GERA (4,903 individuals), stratified by case/control status, to construct an independent replication test, and found a significant effect of rs58389158 on speech reception threshold (SRT; overall GERA meta-analysis p = 1.9x10-6). We also tested variants within exons of 132 other previously-identified hearing loss genes, and identified two common additional significant SNPs: rs2877561 (synonymous change in ILDR1, p = 6.2x10-5), which replicated in the UK Biobank (p = 0.00057), and had a significant GERA SRT (p = 0.00019) and speech discrimination score (SDS; p = 0.0019); and rs9493627 (missense change in EYA4, p = 0.00011) which replicated in the UK Biobank (p = 0.0095), other GERA groups (p = 0.0080), and had a consistent significant result for SRT (p = 0.041) and suggestive result for SDS (p = 0.081). Large cohorts with GWAS data and electronic health records may be a useful method to characterize the genetic architecture of ARHI.

Dataset Information

Genome-wide Association Study of Dimensional Psychopathology Using Electronic Health Records.

Publications

Genome-wide Association Study of Dimensional Psychopathology Using Electronic Health Records.

Similar Datasets

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