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| PMID |
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| TITLE |
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| Multi-ancestry study of the genetics of problematic alcohol use in >1 million individuals. |
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| ABSTRACT |
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| Problematic alcohol use (PAU) is a leading cause of death and disability worldwide. To improve our understanding of the genetics of PAU, we conducted a large cross-ancestry meta-analysis of PAU in 1,079,947 individuals. We observed a high degree of cross-ancestral similarity in the genetic architecture of PAU and identified 110 independent risk variants in within- and cross-ancestry analyses. Cross-ancestry fine-mapping improved the identification of likely causal variants. Prioritizing genes through gene expression and/or chromatin interaction in brain tissues identified multiple genes associated with PAU. We identified existing medications for potential pharmacological studies by drug repurposing analysis. Cross-ancestry polygenic risk scores (PRS) showed better performance in independent sample than single-ancestry PRS. Genetic correlations between PAU and other traits were observed in multiple ancestries, with other substance use traits having the highest correlations. The analysis of diverse ancestries contributed significantly to the findings, and fills an important gap in the literature. |
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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| entrez |
2023/02/07 01:57 |
| pubmed |
2023/02/08 06:00 |
| medline |
2023/02/08 06:01 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Zhou H |
|
Zhou |
Hang |
H |
|
|
| Kember RL |
|
Kember |
Rachel L |
RL |
|
|
| Deak JD |
|
Deak |
Joseph D |
JD |
|
|
| Xu H |
|
Xu |
Heng |
H |
|
|
| Toikumo S |
|
Toikumo |
Sylvanus |
S |
|
|
| Yuan K |
|
Yuan |
Kai |
K |
|
|
| Lind PA |
|
Lind |
Penelope A |
PA |
|
|
| Farajzadeh L |
|
Farajzadeh |
Leila |
L |
|
|
| Wang L |
|
Wang |
Lu |
L |
|
|
| Hatoum AS |
|
Hatoum |
Alexander S |
AS |
|
|
| Johnson J |
|
Johnson |
Jessica |
J |
|
|
| Lee H |
|
Lee |
Hyunjoon |
H |
|
|
| Mallard TT |
|
Mallard |
Travis T |
TT |
|
|
| Xu J |
|
Xu |
Jiayi |
J |
|
|
| Johnston KJA |
|
Johnston |
Keira J A |
KJA |
|
|
| Johnson EC |
|
Johnson |
Emma C |
EC |
|
|
| Galimberti M |
|
Galimberti |
Marco |
M |
|
|
| Dao C |
|
Dao |
Cecilia |
C |
|
|
| Levey DF |
|
Levey |
Daniel F |
DF |
|
|
| Overstreet C |
|
Overstreet |
Cassie |
C |
|
|
| Byrne EM |
|
Byrne |
Enda M |
EM |
|
|
| Gillespie NA |
|
Gillespie |
Nathan A |
NA |
|
|
| Gordon S |
|
Gordon |
Scott |
S |
|
|
| Hickie IB |
|
Hickie |
Ian B |
IB |
|
|
| Whitfield JB |
|
Whitfield |
John B |
JB |
|
|
| Xu K |
|
Xu |
Ke |
K |
|
|
| Zhao H |
|
Zhao |
Hongyu |
H |
|
|
| Huckins LM |
|
Huckins |
Laura M |
LM |
|
|
| Davis LK |
|
Davis |
Lea K |
LK |
|
|
| Sanchez-Roige S |
|
Sanchez-Roige |
Sandra |
S |
|
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| Madden PAF |
|
Madden |
Pamela A F |
PAF |
|
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| Heath AC |
|
Heath |
Andrew C |
AC |
|
|
| Medland SE |
|
Medland |
Sarah E |
SE |
|
|
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
|
| Ge T |
|
Ge |
Tian |
T |
|
|
| Smoller JW |
|
Smoller |
Jordan W |
JW |
|
|
| Hougaard DM |
|
Hougaard |
David M |
DM |
|
|
| Børglum AD |
|
Børglum |
Anders D |
AD |
|
|
| Demontis D |
|
Demontis |
Ditte |
D |
|
|
| Krystal JH |
|
Krystal |
John H |
JH |
|
|
| Gaziano JM |
|
Gaziano |
J Michael |
JM |
|
|
| Edenberg HJ |
|
Edenberg |
Howard J |
HJ |
|
|
| Agrawal A |
|
Agrawal |
Arpana |
A |
|
|
|
Million Veteran Program |
|
|
|
|
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| Justice AC |
|
Justice |
Amy C |
AC |
|
|
| Stein MB |
|
Stein |
Murray B |
MB |
|
|
| Kranzler HR |
|
Kranzler |
Henry R |
HR |
|
|
| Gelernter J |
|
Gelernter |
Joel |
J |
|
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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: Jan |
| DAY: 30 |
| 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 |
|
| GRANTID |
AGENCY |
COUNTRY |
| MC_PC_17228 |
Medical Research Council |
United Kingdom |
| MC_QA137853 |
Medical Research Council |
United Kingdom |
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| GENERAL NOTE |
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| KEYWORDS |
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| CHEMICALS |
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