Evidence map›Paper›PMID 29574260›Full record

ArticleBrain, behavior, and immunity2018

HLA typing using genome wide data reveals susceptibility types for infections in a psychiatric disease enriched sample.

Samuel Parks, Dimitrios Avramopoulos, Jennifer Mulle, John McGrath, Ruihua Wang, Fernando S Goes, Karen Conneely, Ingo Ruczinski, Robert Yolken, Ann E Pulver and 1 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Brain, behavior, and immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
0.8field-weighted citation impact, top 27% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 13 citations in OpenAlex.

  1. Pooled it
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors at 4 institutions in 1 country.

Samuel ParksDept. of Epidemiology, Rollins School of Public Health, USA.
Dimitrios AvramopoulosDepartment of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jennifer MulleDepartment of Human Genetics, Emory University, Atlanta, GA, USA.
John McGrathDepartment of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ruihua WangMcKusick Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Fernando S GoesDepartment of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Karen ConneelyDepartment of Human Genetics, Emory University, Atlanta, GA, USA.
Ingo RuczinskiBloomberg School of Public Heath, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Robert YolkenDepartment of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ann E PulverBloomberg School of Public Heath, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Brad D PearceDept. of Epidemiology, Rollins School of Public Health, USA. Electronic address: bpearce@emory.edu.
Johns Hopkins University · USJohns Hopkins Medicine · USEmory University · USRollins College · US

Funding

1/2 Schizophrenia Heterogeneity and Toxoplasma ExposureR01MH092515 · NIMH · JOHNS HOPKINS UNIVERSITY · PI AVRAMOPOULOS, DIMITRIOS · 2011 to 2013
$1.0M
Cytokine-HPA Interactions During PregnanacyR21MH068513 · NIMH · EMORY UNIVERSITY · PI PEARCE, BRADLEY D · 2004 to 2006
$569k
2/2 Schizophrenia Heterogeneity and Toxoplasma ExposureR01MH092512 · NIMH · EMORY UNIVERSITY · PI PEARCE, BRADLEY D · 2011 to 2013
$487k
NIMH NIH HHS R01 MH092512NIMH NIH HHS R01 MH092515NIMH NIH HHS R21 MH068513
6 · The paper itself

Abstract

backgroundThe infections Toxoplasma gondii (T. gondii), cytomegalovirus, and Herpes Simplex Virus Type 1 (HSV1) are common persistent infections that have been associated with schizophrenia and bipolar disorder. The major histocompatibility complex (MHC, termed HLA in humans) region has been implicated in these infections and these mental illnesses. The interplay of MHC genetics, mental illness, and infection has not been systematically examined in previous research.

methodsIn a cohort of 1636 individuals, we used genome-wide association data to impute 7 HLA types (A, B, C, DRB1, DQA1, DQB1, DPB1), and combined this data with serology data for these infections. We used regression analysis to assess the association between HLA alleles, infections (individually and collectively), and mental disorder status (schizophrenia, bipolar disorder, controls).

resultsAfter Bonferroni correction for multiple comparisons, HLA C∗07:01 was associated with increased HSV1 infection among mentally healthy controls (OR 3.4, p = 0.0007) but not in the schizophrenia or bipolar groups (P > 0.05). For the multiple infection outcome, HLA B∗ 38:01 and HLA C∗12:03 were protective in the healthy controls (OR ≈ 0.4) but did not have a statistically-significant effect in the schizophrenia or bipolar groups. T. gondii had several nominally-significant positive associations, including the haplotypes HLA DRB∗03:01 ∼ HLA DQA∗05:01 ∼ HLA DQB∗02:01 and HLA B∗08:01 ∼ HLA C∗07:01.

conclusionsWe identified HLA types that showed strong and significant associations with neurotropic infections. Since some of these associations depended on mental illness status, the engagement of HLA-related pathways may be altered in schizophrenia due to immunogenetic differences or exposure history.

Indexed as

AdultAllelesBipolar DisorderCytomegalovirusFemaleGene FrequencyGenetic Predisposition to DiseaseGenome-Wide Association StudyHaplotypesHerpesvirus 1, HumanHistocompatibility TestingHLA AntigensHumansInfectionsMaleSchizophreniaHLA AntigensBipolar disorderHerpes virusHistocompatibility antigenMajor histocompatibility complexSchizophreniaToxoplasma

Identifiers

PMID29574260
PMCPMC12919707
OpenAlexW2790789435

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.