Imperial College London

DrAbbasDehghan

Faculty of MedicineSchool of Public Health

Reader in Cardiometabolic Disease Epidemiology
 
 
 
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Contact

 

+44 (0)20 7594 3347a.dehghan CV

 
 
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Location

 

157Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Prins:2016:10.1371/journal.pmed.1001976,
author = {Prins, BP and Abbasi, A and Wong, A and Vaez, A and Nolte, I and Franceschini, N and Stuart, PE and Guterriez, Achury J and Mistry, V and Bradfield, JP and Valdes, AM and Bras, J and Shatunov, A and PAGE, Consortium and International, Stroke Genetics Consortium and Systemic, Sclerosis consortium and Treat, OA consortium and DIAGRAM, Consortium and CARDIoGRAMplusC4D, Consortium and ALS, consortium and International, Parkinsons Disease Genomics Consortium and Autism, Spectrum Disorder Working Group of the Psychiatric Genomics Consortium and CKDGen, consortium and GERAD1, Consortium and International, Consortium for Blood Pressure and Schizophrenia, Working Group of the Psychiatric Genomics Consortium and Inflammation, Working Group of the CHARGE Consortium and Lu, C and Han, B and Raychaudhuri, S and Bevan, S and Mayes, MD and Tsoi, LC and Evangelou, E and Nair, RP and Grant, SF and Polychronakos, C and Radstake, TR and van, Heel DA and Dunstan, ML and Wood, NW and Al-Chalabi, A and Dehg},
doi = {10.1371/journal.pmed.1001976},
journal = {PLOS Medicine},
title = {Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study},
url = {http://dx.doi.org/10.1371/journal.pmed.1001976},
volume = {13},
year = {2016}
}

RIS format (EndNote, RefMan)

TY  - JOUR
AB - BACKGROUND: C-reactive protein (CRP) is associated with immune, cardiometabolic, and psychiatric traits and diseases. Yet it is inconclusive whether these associations are causal. METHODS AND FINDINGS: We performed Mendelian randomization (MR) analyses using two genetic risk scores (GRSs) as instrumental variables (IVs). The first GRS consisted of four single nucleotide polymorphisms (SNPs) in the CRP gene (GRSCRP), and the second consisted of 18 SNPs that were significantly associated with CRP levels in the largest genome-wide association study (GWAS) to date (GRSGWAS). To optimize power, we used summary statistics from GWAS consortia and tested the association of these two GRSs with 32 complex somatic and psychiatric outcomes, with up to 123,865 participants per outcome from populations of European ancestry. We performed heterogeneity tests to disentangle the pleiotropic effect of IVs. A Bonferroni-corrected significance level of less than 0.0016 was considered statistically significant. An observed p-value equal to or less than 0.05 was considered nominally significant evidence for a potential causal association, yet to be confirmed. The strengths (F-statistics) of the IVs were 31.92-3,761.29 and 82.32-9,403.21 for GRSCRP and GRSGWAS, respectively. CRP GRSGWAS showed a statistically significant protective relationship of a 10% genetically elevated CRP level with the risk of schizophrenia (odds ratio [OR] 0.86 [95% CI 0.79-0.94]; p < 0.001). We validated this finding with individual-level genotype data from the schizophrenia GWAS (OR 0.96 [95% CI 0.94-0.98]; p < 1.72 × 10-6). Further, we found that a standardized CRP polygenic risk score (CRPPRS) at p-value thresholds of 1 × 10-4, 0.001, 0.01, 0.05, and 0.1 using individual-level data also showed a protective effect (OR < 1.00) against schizophrenia; the first CRPPRS (built of SNPs with p < 1 × 10-4) showed a statistically significant (p < 2.45 × 10-4) protective effect with
AU - Prins,BP
AU - Abbasi,A
AU - Wong,A
AU - Vaez,A
AU - Nolte,I
AU - Franceschini,N
AU - Stuart,PE
AU - Guterriez,Achury J
AU - Mistry,V
AU - Bradfield,JP
AU - Valdes,AM
AU - Bras,J
AU - Shatunov,A
AU - PAGE,Consortium
AU - International,Stroke Genetics Consortium
AU - Systemic,Sclerosis consortium
AU - Treat,OA consortium
AU - DIAGRAM,Consortium
AU - CARDIoGRAMplusC4D,Consortium
AU - ALS,consortium
AU - International,Parkinsons Disease Genomics Consortium
AU - Autism,Spectrum Disorder Working Group of the Psychiatric Genomics Consortium
AU - CKDGen,consortium
AU - GERAD1,Consortium
AU - International,Consortium for Blood Pressure
AU - Schizophrenia,Working Group of the Psychiatric Genomics Consortium
AU - Inflammation,Working Group of the CHARGE Consortium
AU - Lu,C
AU - Han,B
AU - Raychaudhuri,S
AU - Bevan,S
AU - Mayes,MD
AU - Tsoi,LC
AU - Evangelou,E
AU - Nair,RP
AU - Grant,SF
AU - Polychronakos,C
AU - Radstake,TR
AU - van,Heel DA
AU - Dunstan,ML
AU - Wood,NW
AU - Al-Chalabi,A
AU - Dehghan,A
AU - Hakonarson,H
AU - Markus,HS
AU - Elder,JT
AU - Knight,J
AU - Arking,DE
AU - Spector,TD
AU - Koeleman,BP
AU - van,Duijn CM
AU - Martin,J
AU - Morris,AP
AU - Weersma,RK
AU - Wijmenga,C
AU - Munroe,PB
AU - Perry,JR
AU - Pouget,JG
AU - Jamshidi,Y
AU - Snieder,H
AU - Alizadeh,BZ
DO - 10.1371/journal.pmed.1001976
PY - 2016///
SN - 1549-1277
TI - Investigating the Causal Relationship of C-Reactive Protein with 32 Complex Somatic and Psychiatric Outcomes: A Large-Scale Cross-Consortium Mendelian Randomization Study
T2 - PLOS Medicine
UR - http://dx.doi.org/10.1371/journal.pmed.1001976
UR - http://hdl.handle.net/10044/1/34380
VL - 13
ER -