Dupuis J

References (3)

Title : Overlap of Genetic Risk between Interstitial Lung Abnormalities and Idiopathic Pulmonary Fibrosis - Hobbs_2019_Am.J.Respir.Crit.Care.Med_200_1402
Author(s) : Hobbs BD , Putman RK , Araki T , Nishino M , Gudmundsson G , Gudnason V , Eiriksdottir G , Zilhao Nogueira NR , Dupuis J , Xu H , O'Connor GT , Manichaikul A , Nguyen J , Podolanczuk AJ , Madahar P , Rotter JI , Lederer DJ , Barr RG , Rich SS , Ampleford EJ , Ortega VE , Peters SP , O'Neal WK , Newell JD, Jr. , Bleecker ER , Meyers DA , Allen RJ , Oldham JM , Ma SF , Noth I , Jenkins RG , Maher TM , Hubbard RB , Wain LV , Fingerlin TE , Schwartz DA , Washko GR , Rosas IO , Silverman EK , Hatabu H , Cho MH , Hunninghake GM
Ref : American Journal of Respiratory & Critical Care Medicine , 200 :1402 , 2019
Abstract : Rationale: Interstitial lung abnormalities (ILAs) are associated with the highest genetic risk locus for idiopathic pulmonary fibrosis (IPF); however, the extent to which there are unique associations among individuals with ILAs or additional overlap with IPF is not known.Objectives: To perform a genome-wide association study (GWAS) of ILAs.Methods: ILAs and a subpleural-predominant subtype were assessed on chest computed tomography (CT) scans in the AGES (Age Gene/Environment Susceptibility), COPDGene (Genetic Epidemiology of Chronic Obstructive Pulmonary Disease [COPD]), Framingham Heart, ECLIPSE (Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points), MESA (Multi-Ethnic Study of Atherosclerosis), and SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) studies. We performed a GWAS of ILAs in each cohort and combined the results using a meta-analysis. We assessed for overlapping associations in independent GWASs of IPF.Measurements and Main Results: Genome-wide genotyping data were available for 1,699 individuals with ILAs and 10,274 control subjects. The MUC5B (mucin 5B) promoter variant rs35705950 was significantly associated with both ILAs (P = 2.6 x 10(-27)) and subpleural ILAs (P = 1.6 x 10(-29)). We discovered novel genome-wide associations near IPO11 (rs6886640, P = 3.8 x 10(-8)) and FCF1P3 (rs73199442, P = 4.8 x 10(-8)) with ILAs, and near HTRE1 (rs7744971, P = 4.2 x 10(-8)) with subpleural-predominant ILAs. These novel associations were not associated with IPF. Among 12 previously reported IPF GWAS loci, five (DPP9, DSP, FAM13A, IVD, and MUC5B) were significantly associated (P < 0.05/12) with ILAs.Conclusions: In a GWAS of ILAs in six studies, we confirmed the association with a MUC5B promoter variant and found strong evidence for an effect of previously described IPF loci; however, novel ILA associations were not associated with IPF. These findings highlight common genetically driven biologic pathways between ILAs and IPF, and also suggest distinct ones.
ESTHER : Hobbs_2019_Am.J.Respir.Crit.Care.Med_200_1402
PubMedSearch : Hobbs_2019_Am.J.Respir.Crit.Care.Med_200_1402
PubMedID: 31339356

Title : Eight genetic loci associated with variation in lipoprotein-associated phospholipase A2 mass and activity and coronary heart disease: meta-analysis of genome-wide association studies from five community-based studies - Grallert_2012_Eur.Heart.J_33_238
Author(s) : Grallert H , Dupuis J , Bis JC , Dehghan A , Barbalic M , Baumert J , Lu C , Smith NL , Uitterlinden AG , Roberts R , Khuseyinova N , Schnabel RB , Rice KM , Rivadeneira F , Hoogeveen RC , Fontes JD , Meisinger C , Keaney JF, Jr. , Lemaitre R , Aulchenko YS , Vasan RS , Ellis S , Hazen SL , van Duijn CM , Nelson JJ , Marz W , Schunkert H , McPherson RM , Stirnadel-Farrant HA , Psaty BM , Gieger C , Siscovick D , Hofman A , Illig T , Cushman M , Yamamoto JF , Rotter JI , Larson MG , Stewart AF , Boerwinkle E , Witteman JC , Tracy RP , Koenig W , Benjamin EJ , Ballantyne CM
Ref : Eur Heart J , 33 :238 , 2012
Abstract : AIMS: Lipoprotein-associated phospholipase A2 (Lp-PLA2) generates proinflammatory and proatherogenic compounds in the arterial vascular wall and is a potential therapeutic target in coronary heart disease (CHD). We searched for genetic loci related to Lp-PLA2 mass or activity by a genome-wide association study as part of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. METHODS AND RESULTS: In meta-analyses of findings from five population-based studies, comprising 13 664 subjects, variants at two loci (PLA2G7, CETP) were associated with Lp-PLA2 mass. The strongest signal was at rs1805017 in PLA2G7 [P = 2.4 x 10(-23), log Lp-PLA2 difference per allele (beta): 0.043]. Variants at six loci were associated with Lp-PLA2 activity (PLA2G7, APOC1, CELSR2, LDL, ZNF259, SCARB1), among which the strongest signals were at rs4420638, near the APOE-APOC1-APOC4-APOC2 cluster [P = 4.9 x 10(-30); log Lp-PLA2 difference per allele (beta): -0.054]. There were no significant gene-environment interactions between these eight polymorphisms associated with Lp-PLA2 mass or activity and age, sex, body mass index, or smoking status. Four of the polymorphisms (in APOC1, CELSR2, SCARB1, ZNF259), but not PLA2G7, were significantly associated with CHD in a second study. CONCLUSION: Levels of Lp-PLA2 mass and activity were associated with PLA2G7, the gene coding for this protein. Lipoprotein-associated phospholipase A2 activity was also strongly associated with genetic variants related to low-density lipoprotein cholesterol levels.
ESTHER : Grallert_2012_Eur.Heart.J_33_238
PubMedSearch : Grallert_2012_Eur.Heart.J_33_238
PubMedID: 22003152
Gene_locus related to this paper: human-PLA2G7

Title : Insights from honeybee (Apis mellifera) and fly (Drosophila melanogaster) nicotinic acetylcholine receptors: from genes to behavioral functions - Dupuis_2012_Neurosci.Biobehav.Rev_36_1553
Author(s) : Dupuis J , Louis T , Gauthier M , Raymond V
Ref : Neurosci Biobehav Rev , 36 :1553 , 2012
Abstract : Nicotinic acetylcholine receptors (nAChRs) are widely expressed throughout the central nervous system of insects where they supply fast synaptic excitatory transmission and represent a major target for several insecticides. The unbalance is striking between the abundant literature on nAChR sensitivity to insecticides and the rarity of information regarding their molecular properties and cognitive functions. The recent advent of genome sequencing disclosed that nAChR gene families of insects are rather small-sized compared to vertebrates. Behavioral experiments performed in the honeybee demonstrated that a subpopulation of nAChRs sensitive to the venom alpha-bungarotoxin and permeant to calcium is necessary for the formation of long-term memory. Concomitant data in Drosophila reported that repetitive exposure to nicotine results in a calcium-dependent plasticity of the nAChR-mediated response involving cAMP signaling cascades and indicated that ACh-induced Ca++ currents are modulated by monoamines involved in aversive and appetitive learning. As in vertebrates, in which glutamate and NMDA-type glutamate receptors are involved in experience-associated synaptic plasticity and memory formation, insects could display a comparable system based on ACh and alpha-Bgt-sensitive nAChRs.
ESTHER : Dupuis_2012_Neurosci.Biobehav.Rev_36_1553
PubMedSearch : Dupuis_2012_Neurosci.Biobehav.Rev_36_1553
PubMedID: 22525891