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GWAS Study

Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.

Pardiñas AF, Holmans P, Pocklington AJ et al.

29483656 PubMed ID
GWAS Study Type
265304 Participants
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Chapter I

Publication Details

Comprehensive information about this research publication

Authors

PA
Pardiñas AF
HP
Holmans P
PA
Pocklington AJ
EV
Escott-Price V
RS
Ripke S
CN
Carrera N
LS
Legge SE
BS
Bishop S
CD
Cameron D
HM
Hamshere ML
HJ
Han J
HL
Hubbard L
LA
Lynham A
MK
Mantripragada K
RE
Rees E
MJ
MacCabe JH
MS
McCarroll SA
BB
Baune BT
BG
Breen G
BE
Byrne EM
DU
Dannlowski U
ET
Eley TC
HC
Hayward C
MN
Martin NG
MA
McIntosh AM
PR
Plomin R
PD
Porteous DJ
WN
Wray NR
CA
Caballero A
GD
Geschwind DH
HL
Huckins LM
RD
Ruderfer DM
SE
Santiago E
SP
Sklar P
SE
Stahl EA
WH
Won H
AE
Agerbo E
AT
Als TD
AO
Andreassen OA
BM
Bækvad-Hansen M
MP
Mortensen PB
PC
Pedersen CB
BA
Børglum AD
BJ
Bybjerg-Grauholm J
DS
Djurovic S
DN
Durmishi N
PM
Pedersen MG
GV
Golimbet V
GJ
Grove J
HD
Hougaard DM
MM
Mattheisen M
ME
Molden E
MO
Mors O
NM
Nordentoft M
PM
Pejovic-Milovancevic M
SE
Sigurdsson E
ST
Silagadze T
HC
Hansen CS
SK
Stefansson K
SH
Stefansson H
SS
Steinberg S
TS
Tosato S
WT
Werge T
CD
Collier DA
RD
Rujescu D
KG
Kirov G
OM
Owen MJ
OM
O'Donovan MC
WJ
Walters JTR
Chapter II

Abstract

Summary of the research findings

Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.

40,675 European ancestry cases, 64,643 European ancestry controls

Chapter III

Study Statistics

Key metrics and study information

265304
Total Participants
GWAS
Study Type
Yes
Replicated
1,651 European ancestry cases, 4,111 cases, 142,717 European ancestry controls, 11,507 controls
Replication Participants
European
Ancestry
Georgia, Russian Federation, Denmark, Italy, Serbia, The former Yugoslav Republic of Macedonia, Norway, Iceland, Australia, U.K.
Recruitment Country
Chapter IV

Analysis

Comprehensive review of health and genetic findings

Important Disclaimer: This review has been performed semi-automatically and is provided for informational purposes only. While we strive for accuracy, this analysis may contain errors, omissions, or misinterpretations of the original research. DNA Genics disclaims all liability for any inaccuracies, errors, or consequences arising from the use of this information. Users should independently verify all information and consult original research publications before making any decisions based on this content. This analysis is not intended as a substitute for professional scientific review or medical advice.

Analysis In Progress

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