Evidence map›Paper›PMID 41282233›Full record

ArticleResearch square2025

Ancestry-specific genetic effects on urinary 6-sulfatoxymelatonin: a multi-ancestry GWAS meta-analysis.

Magdalena Żebrowska, Ziwei Zhang, Gwo-Tsann Chuang, Daniel S Evans, Jesse Valliere, Matthew Maher, Jie Hu, Rebecca Richmond, Constance Turman, Jaime E Hart and 13 more

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In one paragraph

Article in Research square, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Magdalena ŻebrowskaMedical University of Vienna.
Ziwei ZhangHarvard T.H. Chan School of Public Health.
Gwo-Tsann ChuangNational Taiwan University Hospital, National Taiwan University.
Daniel S EvansCalifornia Pacific Medical Center.
Jesse ValliereMassachusetts General Hospital.
Matthew MaherMassachusetts General Hospital.
Jie HuHarvard T.H. Chan School of Public Health.
Rebecca RichmondUniversity of Bristol.
Constance TurmanHarvard T.H. Chan School of Public Health.
Jaime E HartHarvard Medical School.
Jacqueline LaneMassachusetts General Hospital.
Loic Le MarchandUniversity of Hawaii Cancer Center.
Lynne WilkensUniversity of Hawaii Cancer Center.
Matthias WielscherMedical University of Vienna.
Christopher HaimanUniversity of Southern California.
Iona ChengUniversity of California, San Francisco.
A Heather EliassenHarvard Medical School.
Katie L StoneCalifornia Pacific Medical Center.
Gregory J TranahCalifornia Pacific Medical Center.
Yi-Cheng ChangNational Taiwan University.
Lorelei Ann MucciHarvard T.H. Chan School of Public Health.
Eva S SchernhammerMedical University of Vienna.
Richa SaxenaHarvard Medical School.

Funding

Statistical MethodsP01CA087969 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, TAMIMI, RULLA M · 2000 to 2019
$77.8M
Validity of Diet and Activity Measures in WomenP01CA055075 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI FUCHS, CHARLES S · 1991 to 2009
$41.8M
Understanding Population Differences in Cancer: The MEC StudyU01CA164973 · NCI · UNIVERSITY OF HAWAII AT MANOA · PI HAIMAN, CHRISTOPHER ALAN, LE MARCHAND, LOIC · 2015 to 2025
$37.4M
Risk Factors for Breast Cancer in Younger NursesR01CA050385 · NCI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI ELIASSEN, A. HEATHER, WILLETT, WALTER C. · 1989 to 2019
$32.3M
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
Cancer Epidemiology Cohort in Male Health ProfessionalsU01CA167552 · NCI · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Lorelei Mucci, Walter C. Willett · 2017 to 2026
$17.0M
Life Course Cancer Epidemiology Cohort in WomenUM1CA176726 · NCI · HARVARD SCHOOL OF PUBLIC HEALTH · PI WILLETT, WALTER C. · 2013 to 2017
$15.7M
P30 Core Grant for Vision ResearchP30EY014104 · NEI · MASSACHUSETTS EYE AND EAR INFIRMARY · PI Janey L Wiggs · 2002 to 2026
$15.1M
RISK FACTORS FOR CVD IN WOMENR01HL034594 · NHLBI · TULANE UNIVERSITY OF LOUISIANA · PI JoAnn Elisabeth Manson, Lu Qi · 1985 to 2026
$13.8M
Dietary Etiology of Heart DiseaseR01HL035464 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI ERIC B RIMM, Qi Sun · 1986 to 2026
$13.6M
Outcomes of Sleep Disorders in Older MenR01HL071194 · NHLBI · UNIVERSITY OF CALIFORNIA SAN FRANCISCO · PI STONE, KATIE L · 2003 to 2013
$12.2M
NCI NIH HHS P01 CA055075NCI NIH HHS P01 CA087969NCI NIH HHS R01 CA049449NCI NIH HHS R01 CA050385NCI NIH HHS R01 CA067262NCI NIH HHS R01 CA131332NCI NIH HHS R03 CA165131NCI NIH HHS U01 CA164973NCI NIH HHS U01 CA167552NCI NIH HHS U01 CA176726NCI NIH HHS UM1 CA176726NCI NIH HHS UM1 CA186107NEI NIH HHS P30 EY014104NEI NIH HHS R01 EY015473NEI NIH HHS R01 EY022305NHGRI NIH HHS U01 HG004728NHLBI NIH HHS R01 HL034594NHLBI NIH HHS R01 HL035464NHLBI NIH HHS R01 HL070837NHLBI NIH HHS R01 HL070838NHLBI NIH HHS R01 HL070839NHLBI NIH HHS R01 HL070841NHLBI NIH HHS R01 HL070842NHLBI NIH HHS R01 HL070847NHLBI NIH HHS R01 HL070848NHLBI NIH HHS R01 HL071194NHLBI NIH HHS R01 HL088521NHLBI NIH HHS R01 HL116854NHLBI NIH HHS R24 HL114473NIA NIH HHS R01 AG030089NIA NIH HHS R01 AG030474NIDCD NIH HHS R03 DC013373NIDDK NIH HHS P01 DK070756
6 · The paper itself

Abstract

Melatonin regulates circadian rhythms, metabolism, and immunity. Its primary metabolite, 6-sulfatoxymelatonin (aMT6s), is a biomarker linked to cancer risk and metabolic disorders. However, genetic determinants of aMT6s remain poorly understood, with only one prior GWAS limited to an East Asian cohort. We conducted the first multi-ancestry genome-wide association meta-analysis of urinary aMT6s, integrating 11,744 participants from five cohorts: East Asians (Taiwan Biobank), European women (Nurses' Health Studies), European men (MrOS), and multiethnic participants (MEC). aMT6s was measured from overnight or first-morning urine samples. Analyses used MR-MEGA and fixed-effects models in METAL. Polygenic risk scores (PRS) were constructed with PRS-CSx and tested for phenome-wide associations in the Mass General Brigham Biobank and UK Biobank. No genome-wide significant loci were identified, and previously reported East Asian signals were not replicated. At suggestive significance, 23 loci emerged, with eight supported by both MR-MEGA and METAL. Two loci (SLIT3 rs1875972 and C12orf55 rs7137724) showed ancestry-specific heterogeneity, underscoring the role of population context. PRS analyses revealed robust associations with type 2 diabetes and sleep duration, linking aMT6s genetics to metabolic and circadian traits. These findings highlight context-dependent genetic architecture of melatonin metabolism and emphasize the importance of ancestry in interpreting biomarker GWAS.

Indexed as

GWASmelatoninmeta-analysismulti-ancestrysulphatoxymelatonin

Identifiers

PMID41282233
PMCPMC12632581

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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.