Evidence map›Paper›PMID 37784116›Full record

ArticleBMC medical genomics2023

Insights into the genetics of menopausal vasomotor symptoms: genome-wide analyses of routinely-collected primary care health records.

Katherine S Ruth, Robin N Beaumont, Jonathan M Locke, Jessica Tyrrell, Carolyn J Crandall, Gareth Hawkes, Timothy M Frayling, Julia K Prague, Kashyap A Patel, Andrew R Wood and 2 more

Open access · goldAbstract read
In one paragraph

Article in BMC medical genomics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
1.2field-weighted citation impact, top 19% 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

3 citing papers in PubMed, 6 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
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

12 authors at 3 institutions in 2 countries.

Katherine S RuthGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK. K.S.Ruth@exeter.ac.uk.
Robin N BeaumontGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Jonathan M LockeGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Jessica TyrrellGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Carolyn J CrandallDivision of General Internal Medicine and Health Services Research, David Geffen School of Medicine at University of California, Los Angeles, CA, 90024, USA.
Gareth HawkesGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Timothy M FraylingGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Julia K PragueExeter Centre of Excellence for Diabetes Research, University of Exeter, Exeter, EX2 5DW, UK.
Kashyap A PatelExeter Centre of Excellence for Diabetes Research, University of Exeter, Exeter, EX2 5DW, UK.
Andrew R WoodGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Michael N WeedonGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
Anna MurrayGenetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, EX2 5DW, UK.
University of Exeter · GBRoyal Devon & Exeter NHS Foundation Trust · GBUniversity of California, Los Angeles · US

Funding

Cancer Research UK 29019Medical Research Council MR/M008924/1
6 · The paper itself

Abstract

backgroundVasomotor symptoms (VMS) can often significantly impact women's quality of life at menopause. In vivo studies have shown that increased neurokinin B (NKB) / neurokinin 3 receptor (NK3R) signalling contributes to VMS, with previous genetic studies implicating the TACR3 gene locus that encodes NK3R. Large-scale genomic analyses offer the possibility of biological insights but few such studies have collected data on VMS, while proxy phenotypes such as hormone replacement therapy (HRT) use are likely to be affected by changes in clinical practice. We investigated the genetic basis of VMS by analysing routinely-collected health records.

methodsWe performed a GWAS of VMS derived from linked primary-care records and cross-sectional self-reported HRT use in up to 153,152 women from UK Biobank, a population-based cohort. In a subset of this cohort (n = 39,356), we analysed exome-sequencing data to test the association with VMS of rare deleterious genetic variants. Finally, we used Mendelian randomisation analysis to investigate the reasons for HRT use over time.

resultsOur GWAS of health-records derived VMS identified a genetic signal near TACR3 associated with a lower risk of VMS (OR=0.76 (95% CI 0.72,0.80) per A allele, P=3.7x10

conclusionsWe provide support for TACR3 in the genetic basis of VMS but unexpectedly find that rare genomic variants predicted to lower NK3R levels did not modify VMS, despite the proven efficacy of NK3R antagonists. Using genomics we demonstrate changes in genetic associations with HRT use over time, arising from a change in clinical practice since the early 2000s, which is likely to reflect a switch from preventing post-menopausal complications in women with earlier menopause to primarily treating VMS. Our study demonstrates that integrating routinely-collected primary care health records and genomic data offers great potential for exploring the genetic basis of symptoms.

Indexed as

Genome-Wide Association StudyHot FlashesCross-Sectional StudiesFemaleHumansMenopausePrimary Health CareQuality of LifeGenome-wide analysesGenome-wide association studyHormone replacement therapyMenopauseVasomotor symptoms

Identifiers

PMID37784116
PMCPMC10546673
OpenAlexW4387252754

What Socratic holds

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LicenceCC BY
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 Socratic graph.