Evidence map›Paper›PMID 41495267›Full record

ArticleCommunications medicine2026

Trans-ancestry GWAS of hot flashes reveals potent treatment target and overlap with psychiatric disorders.

Kathryn E Werwath, Rebecca B Lawn, Madeleine T Salem, Tayden Li, Brittany L Mitchell, Hanyang Shen, Scott D Gordon, Benson Kung, Ciera Stafford, Mytilee Vemuri and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Communications medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
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

18 authors.

Kathryn E Werwath *Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Rebecca B Lawn *Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Cambridge, MA, USA.
Madeleine T SalemDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0009-0004-6259-3902
Tayden LiDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-4553-210X
Brittany L MitchellQueensland Institute of Medical Research, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0002-9050-1516
Hanyang ShenDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3273-9777
Scott D GordonQueensland Institute of Medical Research, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0001-7623-328X
Benson KungDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.
Ciera StaffordDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0009-0009-1438-474X
Mytilee VemuriDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA.ORCID http://orcid.org/0009-0003-0847-4825
Andrew RatanatharathornDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-9855-0438
Joeri MeijsenInstitute for Biological Psychiatry, Copenhagen, Denmark.ORCID http://orcid.org/0000-0002-4161-2199
Aladdin H ShadyabHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
Charles KooperbergDivision of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7986-8560
Karestan C KoenenDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-2978-7655
Carolyn J CrandallDivision of General Internal Medicine and Health Services Research, Dept. of Medicine, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, USA.
Nicholas G MartinQueensland Institute of Medical Research, Brisbane, QLD, Australia.ORCID http://orcid.org/0000-0003-4069-8020
Laramie E DuncanDepartment of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA. laramied@stanford.edu.ORCID http://orcid.org/0000-0003-1131-661X

Funding

Life Course Cancer Epidemiology Cohort in WomenU01CA176726 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 2018 to 2025
$22.4M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Premonopausal Hormone Levels and Risk of Breast CancerR01CA067262 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HANKINSON, SUSAN E · 2002 to 2011
$11.9M
BIOCHEMICAL MARKERS IN THE NURSES'HEALTH STUDY COHORTR01CA049449 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI HANKINSON, SUSAN E · 1989 to 2008
$11.3M
Sex hormones and post-traumatic stress disorder (PTSD)R01MH123486 · NIMH · STANFORD UNIVERSITY · PI DUNCAN, LARAMIE · 2020 to 2024
$2.1M
Sex Chromosome GWAS of Post-Traumatic Stress Disorder (PTSD)R21MH125358 · NIMH · STANFORD UNIVERSITY · PI DUNCAN, LARAMIE · 2021 to 2022
$443k
NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA067262NCI NIH HHS U01 CA176726NCI NIH HHS UM1 CA186107NIMH NIH HHS R01 MH123486NIMH NIH HHS R21 MH125358U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (NIMH) MH125358
6 · The paper itself

Abstract

backgroundMost women experience hot flashes (hot flushes) during the menopause transition. Menopausal hot flashes typically persist for years, and for a sizeable minority of women, are substantially impairing. Genetic investigations can improve understanding of hot flash etiology.

methodsWe conducted a trans-ancestry genome-wide association study (GWAS) of hot flashes (N = 149,560) among post-menopausal women age 35-88. The outcome variable was self-reported hot flashes in four samples (total n = 42,489) and menopausal hormone therapy as a proxy in one sample (n = 107,071). We estimated the heritability of hot flashes and genetic correlations with psychiatric phenotypes using linkage disequilibrium score regression.

resultsIn our trans-ancestry meta-analysis, the top locus lies on chromosome 4 in the neurokinin 3 receptor gene (TACR3, p = 7.2×10

conclusionsThese genomic findings are consistent with independent, robust basic science research which led to a recently developed treatment for hot flashes, namely, a neurokinin 3 receptor antagonist. This non-hormonal class of hot flash drugs blocks the receptor coded for by the top locus reported here (TACR3, the neurokinin 3 receptor gene). Hot flash GWAS results provide an example of how GWAS findings can point to potent treatment targets for complex brain phenotypes.

Identifiers

PMID41495267
PMCPMC12830824

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