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A graph-embedded topic model enables characterization of diverse pain phenotypes among UK biobank individuals.

ABSTRACT: Large biobank repositories of clinical conditions and medications data open opportunities to investigate the phenotypic disease network. We present a graph embedded topic model (GETM). We integrate existing biomedical knowledge graph information in the form of pre-trained graph embedding into the embedded topic model. Via a variational autoencoder framework, we infer patient phenotypic mixture by modeling multi-modal discrete patient medical records. We applied GETM to UK Biobank (UKB) self-reported clinical phenotype data, which contains 443 self-reported medical conditions and 802 medications for 457,461 individuals. Compared to existing methods, GETM demonstrates good imputation performance. With a more focused application on characterizing pain phenotypes, we observe that GETM-inferred phenotypes not only accurately predict the status of chronic musculoskeletal (CMK) pain but also reveal known pain-related topics. Intriguingly, medications and conditions in the cardiovascular category are enriched among the most predictive topics of chronic pain.

SUBMITTER: Wang Y

PROVIDER: S-EPMC9142639 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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A graph-embedded topic model enables characterization of diverse pain phenotypes among UK biobank individuals.

Wang Yuening Y Benavides Rodrigo R Diatchenko Luda L Grant Audrey V AV Li Yue Y

iScience 20220512 6

Large biobank repositories of clinical conditions and medications data open opportunities to investigate the phenotypic disease network. We present a graph embedded topic model (GETM). We integrate existing biomedical knowledge graph information in the form of pre-trained graph embedding into the embedded topic model. Via a variational autoencoder framework, we infer patient phenotypic mixture by modeling multi-modal discrete patient medical records. We applied GETM to UK Biobank (UKB) self-repo ...[more]

PMID: 35637735

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Project description:Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype 'chronic pain grade', have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual's overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches.

Project description:BackgroundThe genealogical histories of individuals within populations are of interest to studies aiming both to uncover detailed pedigree information and overall quantitative population demographic histories. However, the analysis of quantitative details of individual genealogical histories has faced challenges from incomplete available pedigree records and an absence of objective and quantitative details in pedigree information. Although complete pedigree information for most individuals is difficult to track beyond a few generations, it is possible to describe a person's genealogical history using their genetic relatives revealed by identity by descent (IBD) segments-long genomic segments shared by two individuals within a population, which are identical due to inheritance from common ancestors. When modern biobanks collect genotype information for a significant fraction of a population, dense genetic connections of a person can be traced using such IBD segments, offering opportunities to characterize individuals in the context of the underlying populations. Here, we conducted an individual-centric analysis of IBD segments among the UK Biobank participants that represent 0.7% of the UK population.ResultsWe made a high-quality call set of IBD segments over 5 cM among all 500,000 UK Biobank participants. On average, one UK individual shares IBD segments with 14,000 UK Biobank participants, which we refer to as "relatives." Using these segments, approximately 80% of a person's genome can be imputed. We subsequently propose genealogical descriptors based on the genetic connections of relative cohorts of individuals sharing at least one IBD segment and show that such descriptors offer important information about one's genetic makeup, personal genealogical history, and social behavior. Through analysis of relative counts sharing segments at different lengths, we identified a group, potentially British Jews, who has a distinct pattern of familial expansion history. Finally, using the enrichment of relatives in one's neighborhood, we identified regional variations of personal preference favoring living closer to one's extended families.ConclusionsOur analysis revealed genetic makeup, personal genealogical history, and social behaviors at the population scale, opening possibilities for further studies of individual's genetic connections in biobank data.

Dataset Information

A graph-embedded topic model enables characterization of diverse pain phenotypes among UK biobank individuals.

Publications

A graph-embedded topic model enables characterization of diverse pain phenotypes among UK biobank individuals.

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