|
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| PMID |
|
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| TITLE |
|
| Understanding the genetic complexity of puberty timing across the allele frequency spectrum. |
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| ABSTRACT |
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|
|
| Pubertal timing varies considerably and has been associated with a range of health outcomes in later life. To elucidate the underlying biological mechanisms, we performed multi-ancestry genetic analyses in ∼800,000 women, identifying 1,080 independent signals associated with age at menarche. Collectively these loci explained 11% of the trait variance in an independent sample, with women at the top and bottom 1% of polygenic risk exhibiting a ∼11 and ∼14-fold higher risk of delayed and precocious pubertal development, respectively. These common variant analyses were supported by exome sequence analysis of ∼220,000 women, identifying several genes, including rare loss of function variants in which abolished the impact of polygenic risk. Next, we implicated 660 genes in pubertal development using a combination of variant-to-gene mapping approaches and integration with dynamic gene expression data from mouse embryonic GnRH neurons. This included an uncharacterized G-protein coupled receptor , which we demonstrate amplifies signaling of , a key sensor of nutritional status. Finally, we identified several genes, including ovary-expressed genes involved in DNA damage response that co-localize with signals associated with menopause timing, leading us to hypothesize that the ovarian reserve might signal centrally to trigger puberty. Collectively these findings extend our understanding of the biological complexity of puberty timing and highlight body size dependent and independent mechanisms that potentially link reproductive timing to later life disease. |
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| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| medline |
2023/07/28 06:43 |
| pubmed |
2023/07/28 06:42 |
| entrez |
2023/07/28 04:26 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Kentistou KA |
|
Kentistou |
Katherine A |
KA |
|
|
| Kaisinger LR |
|
Kaisinger |
Lena R |
LR |
|
|
| Stankovic S |
|
Stankovic |
Stasa |
S |
|
|
| Vaudel M |
|
Vaudel |
Marc |
M |
|
|
| de Oliveira EM |
|
de Oliveira |
Edson M |
EM |
|
|
| Messina A |
|
Messina |
Andrea |
A |
|
|
| Walters RG |
|
Walters |
Robin G |
RG |
|
|
| Liu X |
|
Liu |
Xiaoxi |
X |
|
|
| Busch AS |
|
Busch |
Alexander S |
AS |
|
|
| Helgason H |
|
Helgason |
Hannes |
H |
|
|
| Thompson DJ |
|
Thompson |
Deborah J |
DJ |
|
|
| Santon F |
|
Santon |
Federico |
F |
|
|
| Petricek KM |
|
Petricek |
Konstantin M |
KM |
|
|
| Zouaghi Y |
|
Zouaghi |
Yassine |
Y |
|
|
| Huang-Doran I |
|
Huang-Doran |
Isabel |
I |
|
|
| Gudbjartsson DF |
|
Gudbjartsson |
Daniel F |
DF |
|
|
| Bratland E |
|
Bratland |
Eirik |
E |
|
|
| Lin K |
|
Lin |
Kuang |
K |
|
|
| Gardner EJ |
|
Gardner |
Eugene J |
EJ |
|
|
| Zhao Y |
|
Zhao |
Yajie |
Y |
|
|
| Jia R |
|
Jia |
Raina |
R |
|
|
| Terao C |
|
Terao |
Chikashi |
C |
|
|
| Riggan M |
|
Riggan |
Margie |
M |
|
|
| Bolla MK |
|
Bolla |
Manjeet K |
MK |
|
|
| Yazdanpanah M |
|
Yazdanpanah |
Mojgan |
M |
|
|
| Yazdanpanah N |
|
Yazdanpanah |
Nahid |
N |
|
|
| Bradfield JP |
|
Bradfield |
Jonath P |
JP |
|
|
| Broer L |
|
Broer |
Linda |
L |
|
|
| Campbell A |
|
Campbell |
Archie |
A |
|
|
| Chasman DI |
|
Chasman |
Daniel I |
DI |
|
|
| Cousminer DL |
|
Cousminer |
Diana L |
DL |
|
|
| Franceschini N |
|
Franceschini |
Nora |
N |
|
|
| Franke LH |
|
Franke |
Lude H |
LH |
|
|
| Girotto G |
|
Girotto |
Giorgia |
G |
|
|
| He C |
|
He |
Chunyan |
C |
|
|
| Järvelin MR |
|
Järvelin |
Marjo-Riitta |
MR |
|
|
| Joshi PK |
|
Joshi |
Peter K |
PK |
|
|
| Kamatani Y |
|
Kamatani |
Yoichiro |
Y |
|
|
| Karlsson R |
|
Karlsson |
Robert |
R |
|
|
| Luan J |
|
Luan |
Jian'an |
J |
|
|
| Lunetta KL |
|
Lunetta |
Kathryn L |
KL |
|
|
| Mägi R |
|
Mägi |
Reedik |
R |
|
|
| Mangino M |
|
Mangino |
Massimo |
M |
|
|
| Medland SE |
|
Medland |
Sarah E |
SE |
|
|
| Meisinger C |
|
Meisinger |
Christa |
C |
|
|
| Noordam R |
|
Noordam |
Raymond |
R |
|
|
| Nutile T |
|
Nutile |
Teresa |
T |
|
|
| Concas MP |
|
Concas |
Maria Pina |
MP |
|
|
| Polašek O |
|
Polašek |
Ozren |
O |
|
|
| Porcu E |
|
Porcu |
Eleonora |
E |
|
|
| Ring SM |
|
Ring |
Susan M |
SM |
|
|
| Sala C |
|
Sala |
Cinzia |
C |
|
|
| Smith AV |
|
Smith |
Albert V |
AV |
|
|
| Tanaka T |
|
Tanaka |
Toshiko |
T |
|
|
| van der Most PJ |
|
van der Most |
Peter J |
PJ |
|
|
| Vitart V |
|
Vitart |
Veronique |
V |
|
|
| Wang CA |
|
Wang |
Carol A |
CA |
|
|
| Willemsen G |
|
Willemsen |
Gonneke |
G |
|
|
| Zygmunt M |
|
Zygmunt |
Marek |
M |
|
|
| Ahearn TU |
|
Ahearn |
Thomas U |
TU |
|
|
| Andrulis IL |
|
Andrulis |
Irene L |
IL |
|
|
| Anton-Culver H |
|
Anton-Culver |
Hoda |
H |
|
|
| Antoniou AC |
|
Antoniou |
Antonis C |
AC |
|
|
| Auer PL |
|
Auer |
Paul L |
PL |
|
|
| Barnes CL |
|
Barnes |
Catriona Lk |
CL |
|
|
| Beckmann MW |
|
Beckmann |
Matthias W |
MW |
|
|
| Berrington A |
|
Berrington |
Amy |
A |
|
|
| Bogdanova NV |
|
Bogdanova |
Natalia V |
NV |
|
|
| Bojesen SE |
|
Bojesen |
Stig E |
SE |
|
|
| Brenner H |
|
Brenner |
Hermann |
H |
|
|
| Buring JE |
|
Buring |
Julie E |
JE |
|
|
| Canzian F |
|
Canzian |
Federico |
F |
|
|
| Chang-Claude J |
|
Chang-Claude |
Jenny |
J |
|
|
| Couch FJ |
|
Couch |
Fergus J |
FJ |
|
|
| Cox A |
|
Cox |
Angela |
A |
|
|
| Crisponi L |
|
Crisponi |
Laura |
L |
|
|
| Czene K |
|
Czene |
Kamila |
K |
|
|
| Daly MB |
|
Daly |
Mary B |
MB |
|
|
| Demerath EW |
|
Demerath |
Ellen W |
EW |
|
|
| Dennis J |
|
Dennis |
Joe |
J |
|
|
| Devilee P |
|
Devilee |
Peter |
P |
|
|
| De Vivo I |
|
De Vivo |
Immaculata |
I |
|
|
| Dörk T |
|
Dörk |
Thilo |
T |
|
|
| Dunning AM |
|
Dunning |
Alison M |
AM |
|
|
| Dwek M |
|
Dwek |
Miriam |
M |
|
|
| Eriksson JG |
|
Eriksson |
Johan G |
JG |
|
|
| Fasching PA |
|
Fasching |
Peter A |
PA |
|
|
| Fernandez-Rhodes L |
|
Fernandez-Rhodes |
Lindsay |
L |
|
|
| Ferreli L |
|
Ferreli |
Liana |
L |
|
|
| Fletcher O |
|
Fletcher |
Olivia |
O |
|
|
| Gago-Dominguez M |
|
Gago-Dominguez |
Manuela |
M |
|
|
| García-Closas M |
|
García-Closas |
Montserrat |
M |
|
|
| García-Sáenz JA |
|
García-Sáenz |
José A |
JA |
|
|
| González-Neira A |
|
González-Neira |
Anna |
A |
|
|
| Grallert H |
|
Grallert |
Harald |
H |
|
|
| Guénel P |
|
Guénel |
Pascal |
P |
|
|
| Haiman CA |
|
Haiman |
Christopher A |
CA |
|
|
| Hall P |
|
Hall |
Per |
P |
|
|
| Hamann U |
|
Hamann |
Ute |
U |
|
|
| Hakonarson H |
|
Hakonarson |
Hakon |
H |
|
|
| Hart RJ |
|
Hart |
Roger J |
RJ |
|
|
| Hickey M |
|
Hickey |
Martha |
M |
|
|
| Hooning MJ |
|
Hooning |
Maartje J |
MJ |
|
|
| Hoppe R |
|
Hoppe |
Reiner |
R |
|
|
| Hopper JL |
|
Hopper |
John L |
JL |
|
|
| Hottenga JJ |
|
Hottenga |
Jouke-Jan |
JJ |
|
|
| Hu FB |
|
Hu |
Frank B |
FB |
|
|
| Hübner H |
|
Hübner |
Hanna |
H |
|
|
| Hunter DJ |
|
Hunter |
David J |
DJ |
|
|
|
ABCTB Investigators |
|
|
|
|
|
| Jernström H |
|
Jernström |
Helena |
H |
|
|
| John EM |
|
John |
Esther M |
EM |
|
|
| Karasik D |
|
Karasik |
David |
D |
|
|
| Khusnutdinova EK |
|
Khusnutdinova |
Elza K |
EK |
|
|
| Kristensen VN |
|
Kristensen |
Vessela N |
VN |
|
|
| Lacey JV |
|
Lacey |
James V |
JV |
|
|
| Lambrechts D |
|
Lambrechts |
Diether |
D |
|
|
| Launer LJ |
|
Launer |
Lenore J |
LJ |
|
|
| Lind PA |
|
Lind |
Penelope A |
PA |
|
|
| Lindblom A |
|
Lindblom |
Annika |
A |
|
|
| Magnusson PK |
|
Magnusson |
Patrik Ke |
PK |
|
|
| Mannermaa A |
|
Mannermaa |
Arto |
A |
|
|
| McCarthy MI |
|
McCarthy |
Mark I |
MI |
|
|
| Meitinger T |
|
Meitinger |
Thomas |
T |
|
|
| Menni C |
|
Menni |
Cristina |
C |
|
|
| Michailidou K |
|
Michailidou |
Kyriaki |
K |
|
|
| Millwood IY |
|
Millwood |
Iona Y |
IY |
|
|
| Milne RL |
|
Milne |
Roger L |
RL |
|
|
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
|
| Nevanlinna H |
|
Nevanlinna |
Heli |
H |
|
|
| Nolte IM |
|
Nolte |
Ilja M |
IM |
|
|
| Nyholt DR |
|
Nyholt |
Dale R |
DR |
|
|
| Obi N |
|
Obi |
Nadia |
N |
|
|
| O'Brien KM |
|
O'Brien |
Katie M |
KM |
|
|
| Offit K |
|
Offit |
Kenneth |
K |
|
|
| Oldehinkel AJ |
|
Oldehinkel |
Albertine J |
AJ |
|
|
| Ostrowski SR |
|
Ostrowski |
Sisse R |
SR |
|
|
| Palotie A |
|
Palotie |
Aarno |
A |
|
|
| Pedersen OB |
|
Pedersen |
Ole B |
OB |
|
|
| Peters A |
|
Peters |
Annette |
A |
|
|
| Pianigiani G |
|
Pianigiani |
Giulia |
G |
|
|
| Plaseska-Karanfilska D |
|
Plaseska-Karanfilska |
Dijana |
D |
|
|
| Pouta A |
|
Pouta |
Anneli |
A |
|
|
| Pozarickij A |
|
Pozarickij |
Alfred |
A |
|
|
| Radice P |
|
Radice |
Paolo |
P |
|
|
| Rennert G |
|
Rennert |
Gad |
G |
|
|
| Rosendaal FR |
|
Rosendaal |
Frits R |
FR |
|
|
| Ruggiero D |
|
Ruggiero |
Daniela |
D |
|
|
| Saloustros E |
|
Saloustros |
Emmanouil |
E |
|
|
| Sandler DP |
|
Sandler |
Dale P |
DP |
|
|
| Schipf S |
|
Schipf |
Sabine |
S |
|
|
| Schmidt CO |
|
Schmidt |
Carsten O |
CO |
|
|
| Schmidt MK |
|
Schmidt |
Marjanka K |
MK |
|
|
| Small K |
|
Small |
Kerrin |
K |
|
|
| Spedicati B |
|
Spedicati |
Beatrice |
B |
|
|
| Stampfer M |
|
Stampfer |
Meir |
M |
|
|
| Stone J |
|
Stone |
Jennifer |
J |
|
|
| Tamimi RM |
|
Tamimi |
Rulla M |
RM |
|
|
| Teras LR |
|
Teras |
Lauren R |
LR |
|
|
| Tikkanen E |
|
Tikkanen |
Emmi |
E |
|
|
| Turman C |
|
Turman |
Constance |
C |
|
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| Vachon CM |
|
Vachon |
Celine M |
CM |
|
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| Wang Q |
|
Wang |
Qin |
Q |
|
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| Winqvist R |
|
Winqvist |
Robert |
R |
|
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| Wolk A |
|
Wolk |
Alicja |
A |
|
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| Zemel BS |
|
Zemel |
Babette S |
BS |
|
|
| Zheng W |
|
Zheng |
Wei |
W |
|
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| van Dijk KW |
|
van Dijk |
Ko W |
KW |
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| Alizadeh BZ |
|
Alizadeh |
Behrooz Z |
BZ |
|
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| Bandinelli S |
|
Bandinelli |
Stefania |
S |
|
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| Boerwinkle E |
|
Boerwinkle |
Eric |
E |
|
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| Boomsma DI |
|
Boomsma |
Dorret I |
DI |
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| Ciullo M |
|
Ciullo |
Marina |
M |
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| Chenevix-Trench G |
|
Chenevix-Trench |
Georgia |
G |
|
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| Cucca F |
|
Cucca |
Francesco |
F |
|
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| Esko T |
|
Esko |
Tõnu |
T |
|
|
| Gieger C |
|
Gieger |
Christian |
C |
|
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| Grant SF |
|
Grant |
Struan Fa |
SF |
|
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| Gudnason V |
|
Gudnason |
Vilmundur |
V |
|
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| Hayward C |
|
Hayward |
Caroline |
C |
|
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| Kolčić I |
|
Kolčić |
Ivana |
I |
|
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| Kraft P |
|
Kraft |
Peter |
P |
|
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| Lawlor DA |
|
Lawlor |
Deborah A |
DA |
|
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| Martin NG |
|
Martin |
Nicholas G |
NG |
|
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| Nøhr EA |
|
Nøhr |
Ellen A |
EA |
|
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| Pedersen NL |
|
Pedersen |
Nancy L |
NL |
|
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| Pennell CE |
|
Pennell |
Craig E |
CE |
|
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| Ridker PM |
|
Ridker |
Paul M |
PM |
|
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| Robino A |
|
Robino |
Antonietta |
A |
|
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| Snieder H |
|
Snieder |
Harold |
H |
|
|
| Sovio U |
|
Sovio |
Ulla |
U |
|
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| Spector TD |
|
Spector |
Tim D |
TD |
|
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| Stöckl D |
|
Stöckl |
Doris |
D |
|
|
| Sudlow C |
|
Sudlow |
Cathie |
C |
|
|
| Timpson NJ |
|
Timpson |
Nic J |
NJ |
|
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| Toniolo D |
|
Toniolo |
Daniela |
D |
|
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| Uitterlinden A |
|
Uitterlinden |
André |
A |
|
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| Ulivi S |
|
Ulivi |
Sheila |
S |
|
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| Völzke H |
|
Völzke |
Henry |
H |
|
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| Wareham NJ |
|
Wareham |
Nicholas J |
NJ |
|
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| Widen E |
|
Widen |
Elisabeth |
E |
|
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| Wilson JF |
|
Wilson |
James F |
JF |
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Lifelines Cohort Study |
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Danish Blood Donor study |
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Ovarian Cancer Association Consortium |
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Breast Cancer Association Consortium |
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Biobank Japan Project |
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China Kadoorie Biobank Collaborative Group |
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| Pharoah PD |
|
Pharoah |
Paul Dp |
PD |
|
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| Li L |
|
Li |
Liming |
L |
|
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| Easton DF |
|
Easton |
Douglas F |
DF |
|
|
| Njølstad P |
|
Njølstad |
Pål |
P |
|
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| Sulem P |
|
Sulem |
Patrick |
P |
|
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| Murabito JM |
|
Murabito |
Joanne M |
JM |
|
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| Murray A |
|
Murray |
Anna |
A |
|
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| Manousaki D |
|
Manousaki |
Despoina |
D |
|
|
| Juul A |
|
Juul |
Anders |
A |
|
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| Erikstrup C |
|
Erikstrup |
Christian |
C |
|
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| Stefansson K |
|
Stefansson |
Kari |
K |
|
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| Horikoshi M |
|
Horikoshi |
Momoko |
M |
|
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| Chen Z |
|
Chen |
Zhengming |
Z |
|
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| Farooqi IS |
|
Farooqi |
I Sadaf |
IS |
|
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| Pitteloud N |
|
Pitteloud |
Nelly |
N |
|
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| Johansson S |
|
Johansson |
Stefan |
S |
|
|
| Day FR |
|
Day |
Felix R |
FR |
|
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| Perry JR |
|
Perry |
John Rb |
JR |
|
|
| Ong KK |
|
Ong |
Ken K |
KK |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: |
| ISSUE: |
| TITLE: medRxiv : the preprint server for health sciences |
| ISOABBREVIATION: medRxiv |
| YEAR: 2023 |
| MONTH: Jun |
| DAY: 20 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: |
| ISSNTYPE: |
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| MEDLINE JOURNAL |
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| MEDLINETA: medRxiv |
| COUNTRY: United States |
| ISSNLINKING: |
| NLMUNIQUEID: 101767986 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Preprint |
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| COMMENTS AND CORRECTIONS |
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| GRANTS |
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| GENERAL NOTE |
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| KEYWORDS |
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| MESH HEADINGS |
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| SUPPLEMENTARY MESH |
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| GENE SYMBOLS |
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| CHEMICALS |
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| OTHER ID's |
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