Inference of Causal Relationships Between Genetic Risk Factors for Cardiometabolic Phenotypes and Female-Specific Health Conditions.
Mendelian randomization
cardiometabolic diseases
female health conditions
genomic burden
polygenic risk scores
Journal
Journal of the American Heart Association
ISSN: 2047-9980
Titre abrégé: J Am Heart Assoc
Pays: England
ID NLM: 101580524
Informations de publication
Date de publication:
07 03 2023
07 03 2023
Historique:
pubmed:
28
2
2023
medline:
10
3
2023
entrez:
27
2
2023
Statut:
ppublish
Résumé
Background Cardiometabolic diseases are highly comorbid, but their relationship with female-specific or overwhelmingly female-predominant health conditions (breast cancer, endometriosis, pregnancy complications) is understudied. This study aimed to estimate the cross-trait genetic overlap and influence of genetic burden of cardiometabolic traits on health conditions unique to women. Methods and Results Using electronic health record data from 71 008 ancestrally diverse women, we examined relationships between 23 obstetrical/gynecological conditions and 4 cardiometabolic phenotypes (body mass index, coronary artery disease, type 2 diabetes, and hypertension) by performing 4 analyses: (1) cross-trait genetic correlation analyses to compare genetic architecture, (2) polygenic risk score-based association tests to characterize shared genetic effects on disease risk, (3) Mendelian randomization for significant associations to assess cross-trait causal relationships, and (4) chronology analyses to visualize the timeline of events unique to groups of women with high and low genetic burden for cardiometabolic traits and highlight the disease prevalence in risk groups by age. We observed 27 significant associations between cardiometabolic polygenic scores and obstetrical/gynecological conditions (body mass index and endometrial cancer, body mass index and polycystic ovarian syndrome, type 2 diabetes and gestational diabetes, type 2 diabetes and polycystic ovarian syndrome). Mendelian randomization analysis provided additional evidence of independent causal effects. We also identified an inverse association between coronary artery disease and breast cancer. High cardiometabolic polygenic scores were associated with early development of polycystic ovarian syndrome and gestational hypertension. Conclusions We conclude that polygenic susceptibility to cardiometabolic traits is associated with elevated risk of certain female-specific health conditions.
Identifiants
pubmed: 36846987
doi: 10.1161/JAHA.121.026561
pmc: PMC10111435
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
e026561Subventions
Organisme : NHGRI NIH HHS
ID : U01 HG006379
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG011175
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG008680
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG011176
Pays : United States
Organisme : NHGRI NIH HHS
ID : U01 HG011172
Pays : United States
Investigateurs
Goncalo Abecasis
(G)
Aris Baras
(A)
Michael Cantor
(M)
Giovanni Coppola
(G)
Andrew Deubler
(A)
Aris Economides
(A)
Katia Karalis
(K)
Luca A Lotta
(LA)
John D Overton
(JD)
Jeffrey G Reid
(JG)
Katherine Siminovitch
(K)
Alan Shuldiner
(A)
Christina Beechert
(C)
Caitlin Forsythe
(C)
Erin D Fuller
(ED)
Zhenhua Gu
(Z)
Michael Lattari
(M)
Alexander Lopez
(A)
John D Overton
(JD)
Maria Sotiropoulos Padilla
(MS)
Manasi Pradhan
(M)
Kia Manoochehri
(K)
Thomas D Schleicher
(TD)
Louis Widom
(L)
Sarah E Wolf
(SE)
Ricardo H Ulloa
(RH)
Amelia Averitt
(A)
Nilanjana Banerjee
(N)
Michael Cantor
(M)
Dadong Li
(D)
Sameer Malhotra
(S)
Deepika Sharma
(D)
Jeffrey Staples
(J)
Xiaodong Bai
(X)
Suganthi Balasubramanian
(S)
Suying Bao
(S)
Boris Boutkov
(B)
Siying Chen
(S)
Gisu Eom
(G)
Lukas Habegger
(L)
Alicia Hawes
(A)
Shareef Khalid
(S)
Olga Krasheninina
(O)
Rouel Lanche
(R)
Adam J Mansfield
(AJ)
Evan K Maxwell
(EK)
George Mitra
(G)
Mona Nafde
(M)
Sean O'Keeffe
(S)
Max Orelus
(M)
Razvan Panea
(R)
Tommy Polanco
(T)
Ayesha Rasool
(A)
Jeffrey G Reid
(JG)
William Salerno
(W)
Jeffrey C Staples
(JC)
Kathie Sun
(K)
Goncalo Abecasis
(G)
Joshua Backman
(J)
Amy Damask
(A)
Lee Dobbyn
(L)
Manuel Allen Revez Ferreira
(MAR)
Arkopravo Ghosh
(A)
Christopher Gillies
(C)
Lauren Gurski
(L)
Eric Jorgenson
(E)
Hyun Min Kang
(HM)
Michael Kessler
(M)
Jack Kosmicki
(J)
Alexander Li
(A)
Nan Lin
(N)
Daren Liu
(D)
Adam Locke
(A)
Jonathan Marchini
(J)
Anthony Marcketta
(A)
Joelle Mbatchou
(J)
Arden Moscati
(A)
Charles Paulding
(C)
Carlo Sidore
(C)
Eli Stahl
(E)
Kyoko Watanabe
(K)
Bin Ye
(B)
Blair Zhang
(B)
Andrey Ziyatdinov
(A)
Ariane Ayer
(A)
Aysegul Guvenek
(A)
George Hindy
(G)
Giovanni Coppola
(G)
Jan Freudenberg
(J)
Jonas Bovijn
(J)
Katherine Siminovitch
(K)
Kavita Praveen
(K)
Luca A Lotta
(LA)
Manav Kapoor
(M)
Mary Haas
(M)
Moeen Riaz
(M)
Niek Verweij
(N)
Olukayode Sosina
(O)
Parsa Akbari
(P)
Priyanka Nakka
(P)
Sahar Gelfman
(S)
Sujit Gokhale
(S)
Tanima De
(T)
Veera Rajagopal
(V)
Alan Shuldiner
(A)
Bin Ye
(B)
Gannie Tzoneva
(G)
Juan Rodriguez-Flores
(J)
Shek Man Chim
(SM)
Valerio Donato
(V)
Aris Economides
(A)
Daniel Fernandez
(D)
Giusy Della Gatta
(GD)
Alessandro Di Gioia
(A)
Kristen Howell
(K)
Katia Karalis
(K)
Lori Khrimian
(L)
Minhee Kim
(M)
Hector Martinez
(H)
Lawrence Miloscio
(L)
Sheilyn Nunez
(S)
Elias Pavlopoulos
(E)
Trikaldarshi Persaud
(T)
Esteban Chen
(E)
Marcus B Jones
(MB)
Michelle G LeBlanc
(MG)
Jason Mighty
(J)
Lyndon J Mitnaul
(LJ)
Nirupama Nishtala
(N)
Nadia Rana
(N)
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