@article {1087, title = {Common variants at ten loci influence QT interval duration in the QTGEN Study.}, journal = {Nat Genet}, volume = {41}, year = {2009}, month = {2009 Apr}, pages = {399-406}, abstract = {

QT interval duration, reflecting myocardial repolarization on the electrocardiogram, is a heritable risk factor for sudden cardiac death and drug-induced arrhythmias. We conducted a meta-analysis of three genome-wide association studies in 13,685 individuals of European ancestry from the Framingham Heart Study, the Rotterdam Study and the Cardiovascular Health Study, as part of the QTGEN consortium. We observed associations at P < 5 x 10(-8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and mendelian long-QT syndromes. Associations were found at five newly identified loci, including 16q21 near NDRG4 and GINS3, 6q22 near PLN, 1p36 near RNF207, 16p13 near LITAF and 17q12 near LIG3 and RFFL. Collectively, the 14 independent variants at these 10 loci explain 5.4-6.5\% of the variation in QT interval. These results, together with an accompanying paper, offer insights into myocardial repolarization and suggest candidate genes that could predispose to sudden cardiac death and drug-induced arrhythmias.

}, keywords = {Adaptor Proteins, Signal Transducing, Adult, Aged, Arrhythmias, Cardiac, Chromosome Mapping, Death, Sudden, Cardiac, Electroencephalography, ERG1 Potassium Channel, Ether-A-Go-Go Potassium Channels, European Continental Ancestry Group, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Humans, KCNQ1 Potassium Channel, Meta-Analysis as Topic, Muscle Proteins, NAV1.5 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Potassium Channels, Voltage-Gated, Risk Factors, Sodium Channels}, issn = {1546-1718}, doi = {10.1038/ng.364}, author = {Newton-Cheh, Christopher and Eijgelsheim, Mark and Rice, Kenneth M and de Bakker, Paul I W and Yin, Xiaoyan and Estrada, Karol and Bis, Joshua C and Marciante, Kristin and Rivadeneira, Fernando and Noseworthy, Peter A and Sotoodehnia, Nona and Smith, Nicholas L and Rotter, Jerome I and Kors, Jan A and Witteman, Jacqueline C M and Hofman, Albert and Heckbert, Susan R and O{\textquoteright}Donnell, Christopher J and Uitterlinden, Andr{\'e} G and Psaty, Bruce M and Lumley, Thomas and Larson, Martin G and Stricker, Bruno H Ch} } @article {1077, title = {Genetic variations in nitric oxide synthase 1 adaptor protein are associated with sudden cardiac death in US white community-based populations.}, journal = {Circulation}, volume = {119}, year = {2009}, month = {2009 Feb 24}, pages = {940-51}, abstract = {

BACKGROUND: The ECG QT interval is associated with risk of sudden cardiac death (SCD). A previous genome-wide association study demonstrated that allelic variants (rs10494366 and rs4657139) in the nitric oxide synthase 1 adaptor protein (NOS1AP), which encodes a carboxy-terminal PDZ ligand of neuronal nitric oxide synthase, are associated with the QT interval in white adults. The present analysis was conducted to validate the association between NOS1AP variants and the QT interval and to examine the association with SCD in a combined population of 19 295 black and white adults from the Atherosclerosis Risk In Communities Study and the Cardiovascular Health Study.

METHODS AND RESULTS: We examined 19 tagging single-nucleotide polymorphisms in the genomic blocks containing rs10494366 and rs4657139 in NOS1AP. SCD was defined as a sudden pulseless condition of cardiac origin in a previously stable individual. General linear models and Cox proportional hazards regression models were used. Multiple single-nucleotide polymorphisms in NOS1AP, including rs10494366, rs4657139, and rs16847548, were significantly associated with adjusted QT interval in whites (P<0.0001). In whites, after adjustment for age, sex, and study, the relative hazard of SCD associated with each C allele at rs16847548 was 1.31 (95\% confidence interval 1.10 to 1.56, P=0.002), assuming an additive model. In addition, a downstream neighboring single-nucleotide polymorphism, rs12567209, which was not correlated with rs16847548 or QT interval, was also independently associated with SCD in whites (relative hazard 0.57, 95\% confidence interval 0.39 to 0.83, P=0.003). Adjustment for QT interval and coronary heart disease risk factors attenuated but did not eliminate the association between rs16847548 and SCD, and such adjustment had no effect on the association between rs12567209 and SCD. No significant associations between tagging single-nucleotide polymorphisms in NOS1AP and either QT interval or SCD were observed in blacks.

CONCLUSIONS: In a combined analysis of 2 population-based prospective cohort studies, sequence variations in NOS1AP were associated with baseline QT interval and the risk of SCD in white US adults.

}, keywords = {Adaptor Proteins, Signal Transducing, Aged, Death, Sudden, Cardiac, Electrocardiography, European Continental Ancestry Group, Genotype, Humans, Middle Aged, Polymorphism, Single Nucleotide, Risk Factors}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.108.791723}, author = {Kao, W H Linda and Arking, Dan E and Post, Wendy and Rea, Thomas D and Sotoodehnia, Nona and Prineas, Ronald J and Bishe, Bryan and Doan, Betty Q and Boerwinkle, Eric and Psaty, Bruce M and Tomaselli, Gordon F and Coresh, Josef and Siscovick, David S and Marb{\'a}n, Eduardo and Spooner, Peter M and Burke, Gregory L and Chakravarti, Aravinda} } @article {1074, title = {Multiple independent genetic factors at NOS1AP modulate the QT interval in a multi-ethnic population.}, journal = {PLoS One}, volume = {4}, year = {2009}, month = {2009}, pages = {e4333}, abstract = {

Extremes of electrocardiographic QT interval are associated with increased risk for sudden cardiac death (SCD); thus, identification and characterization of genetic variants that modulate QT interval may elucidate the underlying etiology of SCD. Previous studies have revealed an association between a common genetic variant in NOS1AP and QT interval in populations of European ancestry, but this finding has not been extended to other ethnic populations. We sought to characterize the effects of NOS1AP genetic variants on QT interval in the multi-ethnic population-based Dallas Heart Study (DHS, n = 3,072). The SNP most strongly associated with QT interval in previous samples of European ancestry, rs16847548, was the most strongly associated in White (P = 0.005) and Black (P = 3.6 x 10(-5)) participants, with the same direction of effect in Hispanics (P = 0.17), and further showed a significant SNP x sex-interaction (P = 0.03). A second SNP, rs16856785, uncorrelated with rs16847548, was also associated with QT interval in Blacks (P = 0.01), with qualitatively similar results in Whites and Hispanics. In a previously genotyped cohort of 14,107 White individuals drawn from the combined Atherosclerotic Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) cohorts, we validated both the second locus at rs16856785 (P = 7.63 x 10(-8)), as well as the sex-interaction with rs16847548 (P = 8.68 x 10(-6)). These data extend the association of genetic variants in NOS1AP with QT interval to a Black population, with similar trends, though not statistically significant at P<0.05, in Hispanics. In addition, we identify a strong sex-interaction and the presence of a second independent site within NOS1AP associated with the QT interval. These results highlight the consistent and complex role of NOS1AP genetic variants in modulating QT interval.

}, keywords = {Adaptor Proteins, Signal Transducing, Adolescent, Adult, African Americans, Aged, Death, Sudden, Cardiac, Electrocardiography, Ethnic Groups, European Continental Ancestry Group, Female, Genome-Wide Association Study, Heart Diseases, Heart Rate, Hispanic Americans, Humans, Linear Models, Linkage Disequilibrium, Male, Middle Aged, Polymorphism, Single Nucleotide, Sex Factors, Young Adult}, issn = {1932-6203}, doi = {10.1371/journal.pone.0004333}, author = {Arking, Dan E and Khera, Amit and Xing, Chao and Kao, W H Linda and Post, Wendy and Boerwinkle, Eric and Chakravarti, Aravinda} } @article {1336, title = {Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.}, journal = {PLoS Genet}, volume = {7}, year = {2011}, month = {2011 Sep}, pages = {e1002292}, abstract = {

Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.

}, keywords = {Adaptor Proteins, Signal Transducing, Adult, Aged, Chronic Disease, Creatinine, European Continental Ancestry Group, Female, Follow-Up Studies, Genetic Association Studies, Humans, Kidney Diseases, Kidney Failure, Chronic, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptor, Epidermal Growth Factor, Uromodulin}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1002292}, author = {B{\"o}ger, Carsten A and Gorski, Mathias and Li, Man and Hoffmann, Michael M and Huang, Chunmei and Yang, Qiong and Teumer, Alexander and Krane, Vera and O{\textquoteright}Seaghdha, Conall M and Kutalik, Zolt{\'a}n and Wichmann, H-Erich and Haak, Thomas and Boes, Eva and Coassin, Stefan and Coresh, Josef and Kollerits, Barbara and Haun, Margot and Paulweber, Bernhard and K{\"o}ttgen, Anna and Li, Guo and Shlipak, Michael G and Powe, Neil and Hwang, Shih-Jen and Dehghan, Abbas and Rivadeneira, Fernando and Uitterlinden, Andre and Hofman, Albert and Beckmann, Jacques S and Kr{\"a}mer, Bernhard K and Witteman, Jacqueline and Bochud, Murielle and Siscovick, David and Rettig, Rainer and Kronenberg, Florian and Wanner, Christoph and Thadhani, Ravi I and Heid, Iris M and Fox, Caroline S and Kao, W H} } @article {6089, title = {Genome-wide association study for circulating levels of PAI-1 provides novel insights into its regulation.}, journal = {Blood}, volume = {120}, year = {2012}, month = {2012 Dec 06}, pages = {4873-81}, abstract = {

We conducted a genome-wide association study to identify novel associations between genetic variants and circulating plasminogen activator inhibitor-1 (PAI-1) concentration, and examined functional implications of variants and genes that were discovered. A discovery meta-analysis was performed in 19 599 subjects, followed by replication analysis of genome-wide significant (P < 5 {\texttimes} 10(-8)) single nucleotide polymorphisms (SNPs) in 10 796 independent samples. We further examined associations with type 2 diabetes and coronary artery disease, assessed the functional significance of the SNPs for gene expression in human tissues, and conducted RNA-silencing experiments for one novel association. We confirmed the association of the 4G/5G proxy SNP rs2227631 in the promoter region of SERPINE1 (7q22.1) and discovered genome-wide significant associations at 3 additional loci: chromosome 7q22.1 close to SERPINE1 (rs6976053, discovery P = 3.4 {\texttimes} 10(-10)); chromosome 11p15.2 within ARNTL (rs6486122, discovery P = 3.0 {\texttimes} 10(-8)); and chromosome 3p25.2 within PPARG (rs11128603, discovery P = 2.9 {\texttimes} 10(-8)). Replication was achieved for the 7q22.1 and 11p15.2 loci. There was nominal association with type 2 diabetes and coronary artery disease at ARNTL (P < .05). Functional studies identified MUC3 as a candidate gene for the second association signal on 7q22.1. In summary, SNPs in SERPINE1 and ARNTL and an SNP associated with the expression of MUC3 were robustly associated with circulating levels of PAI-1.

}, keywords = {Adaptor Proteins, Signal Transducing, ARNTL Transcription Factors, ATPases Associated with Diverse Cellular Activities, Cell Line, Cell Line, Tumor, Cohort Studies, Coronary Artery Disease, Diabetes Mellitus, Type 2, Gene Expression Profiling, Gene Expression Regulation, Gene Frequency, Genome-Wide Association Study, Genotype, Humans, LIM Domain Proteins, Meta-Analysis as Topic, Monocytes, Mucin-3, Plasminogen Activator Inhibitor 1, Polymorphism, Single Nucleotide, PPAR gamma, Proteasome Endopeptidase Complex, RNA Interference, Transcription Factors}, issn = {1528-0020}, doi = {10.1182/blood-2012-06-436188}, author = {Huang, Jie and Sabater-Lleal, Maria and Asselbergs, Folkert W and Tregouet, David and Shin, So-Youn and Ding, Jingzhong and Baumert, Jens and Oudot-Mellakh, Tiphaine and Folkersen, Lasse and Johnson, Andrew D and Smith, Nicholas L and Williams, Scott M and Ikram, Mohammad A and Kleber, Marcus E and Becker, Diane M and Truong, Vinh and Mychaleckyj, Josyf C and Tang, Weihong and Yang, Qiong and Sennblad, Bengt and Moore, Jason H and Williams, Frances M K and Dehghan, Abbas and Silbernagel, G{\"u}nther and Schrijvers, Elisabeth M C and Smith, Shelly and Karakas, Mahir and Tofler, Geoffrey H and Silveira, Angela and Navis, Gerjan J and Lohman, Kurt and Chen, Ming-Huei and Peters, Annette and Goel, Anuj and Hopewell, Jemma C and Chambers, John C and Saleheen, Danish and Lundmark, Per and Psaty, Bruce M and Strawbridge, Rona J and Boehm, Bernhard O and Carter, Angela M and Meisinger, Christa and Peden, John F and Bis, Joshua C and McKnight, Barbara and Ohrvik, John and Taylor, Kent and Franzosi, Maria Grazia and Seedorf, Udo and Collins, Rory and Franco-Cereceda, Anders and Syv{\"a}nen, Ann-Christine and Goodall, Alison H and Yanek, Lisa R and Cushman, Mary and M{\"u}ller-Nurasyid, Martina and Folsom, Aaron R and Basu, Saonli and Matijevic, Nena and van Gilst, Wiek H and Kooner, Jaspal S and Hofman, Albert and Danesh, John and Clarke, Robert and Meigs, James B and Kathiresan, Sekar and Reilly, Muredach P and Klopp, Norman and Harris, Tamara B and Winkelmann, Bernhard R and Grant, Peter J and Hillege, Hans L and Watkins, Hugh and Spector, Timothy D and Becker, Lewis C and Tracy, Russell P and M{\"a}rz, Winfried and Uitterlinden, Andr{\'e} G and Eriksson, Per and Cambien, Francois and Morange, Pierre-Emmanuel and Koenig, Wolfgang and Soranzo, Nicole and van der Harst, Pim and Liu, Yongmei and O{\textquoteright}Donnell, Christopher J and Hamsten, Anders} } @article {6290, title = {Genetic variants associated with fasting glucose and insulin concentrations in an ethnically diverse population: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.}, journal = {BMC Med Genet}, volume = {14}, year = {2013}, month = {2013 Sep 25}, pages = {98}, abstract = {

BACKGROUND: Multiple genome-wide association studies (GWAS) within European populations have implicated common genetic variants associated with insulin and glucose concentrations. In contrast, few studies have been conducted within minority groups, which carry the highest burden of impaired glucose homeostasis and type 2 diabetes in the U.S.

METHODS: As part of the {\textquoteright}Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we investigated the association of up to 10 GWAS-identified single nucleotide polymorphisms (SNPs) in 8 genetic regions with glucose or insulin concentrations in up to 36,579 non-diabetic subjects including 23,323 European Americans (EA) and 7,526 African Americans (AA), 3,140 Hispanics, 1,779 American Indians (AI), and 811 Asians. We estimated the association between each SNP and fasting glucose or log-transformed fasting insulin, followed by meta-analysis to combine results across PAGE sites.

RESULTS: Overall, our results show that 9/9 GWAS SNPs are associated with glucose in EA (p = 0.04 to 9 {\texttimes} 10-15), versus 3/9 in AA (p= 0.03 to 6 {\texttimes} 10-5), 3/4 SNPs in Hispanics, 2/4 SNPs in AI, and 1/2 SNPs in Asians. For insulin we observed a significant association with rs780094/GCKR in EA, Hispanics and AI only.

CONCLUSIONS: Generalization of results across multiple racial/ethnic groups helps confirm the relevance of some of these loci for glucose and insulin metabolism. Lack of association in non-EA groups may be due to insufficient power, or to unique patterns of linkage disequilibrium.

}, keywords = {Adaptor Proteins, Signal Transducing, Adult, African Americans, Aged, Alleles, Asian Continental Ancestry Group, Blood Glucose, Diabetes Mellitus, Type 2, European Continental Ancestry Group, Female, Gene Frequency, Genetic Loci, Genome-Wide Association Study, Genomics, Hispanic Americans, Humans, Indians, North American, Insulin, Male, Middle Aged, Polymorphism, Single Nucleotide, Transcription Factor 7-Like 2 Protein}, issn = {1471-2350}, doi = {10.1186/1471-2350-14-98}, author = {Fesinmeyer, Megan D and Meigs, James B and North, Kari E and Schumacher, Fredrick R and B{\r u}zkov{\'a}, Petra and Franceschini, Nora and Haessler, Jeffrey and Goodloe, Robert and Spencer, Kylee L and Voruganti, Venkata Saroja and Howard, Barbara V and Jackson, Rebecca and Kolonel, Laurence N and Liu, Simin and Manson, JoAnn E and Monroe, Kristine R and Mukamal, Kenneth and Dilks, Holli H and Pendergrass, Sarah A and Nato, Andrew and Wan, Peggy and Wilkens, Lynne R and Le Marchand, Lo{\"\i}c and Ambite, Jose Luis and Buyske, Steven and Florez, Jose C and Crawford, Dana C and Hindorff, Lucia A and Haiman, Christopher A and Peters, Ulrike and Pankow, James S} } @article {6628, title = {A systematic mapping approach of 16q12.2/FTO and BMI in more than 20,000 African Americans narrows in on the underlying functional variation: results from the Population Architecture using Genomics and Epidemiology (PAGE) study.}, journal = {PLoS Genet}, volume = {9}, year = {2013}, month = {2013}, pages = {e1003171}, abstract = {

Genetic variants in intron 1 of the fat mass- and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI-associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped a 646-kb region, encompassing the large FTO gene and the flanking gene RPGRIP1L by investigating a total of 3,756 variants (1,529 genotyped and 2,227 imputed variants) in 20,488 AAs across five studies. We observed associations between BMI and variants in the known FTO intron 1 locus: the SNP with the most significant p-value, rs56137030 (8.3 {\texttimes} 10(-6)) had not been highlighted in previous studies. While rs56137030was correlated at r(2)>0.5 with 103 SNPs in Europeans (including the GWAS index SNPs), this number was reduced to 28 SNPs in AA. Among rs56137030 and the 28 correlated SNPs, six were located within candidate intronic regulatory elements, including rs1421085, for which we predicted allele-specific binding affinity for the transcription factor CUX1, which has recently been implicated in the regulation of FTO. We did not find strong evidence for a second independent signal in the broader region. In summary, this large fine-mapping study in AA has substantially reduced the number of common alleles that are likely to be functional candidates of the known FTO locus. Importantly our study demonstrated that comprehensive fine-mapping in AA provides a powerful approach to narrow in on the functional candidate(s) underlying the initial GWAS findings in European populations.

}, keywords = {Adaptor Proteins, Signal Transducing, Adult, African Americans, Aged, Aged, 80 and over, Alleles, Body Mass Index, Chromosome Mapping, Continental Population Groups, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, Metagenomics, Middle Aged, Obesity, Proteins}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1003171}, author = {Peters, Ulrike and North, Kari E and Sethupathy, Praveen and Buyske, Steve and Haessler, Jeff and Jiao, Shuo and Fesinmeyer, Megan D and Jackson, Rebecca D and Kuller, Lew H and Rajkovic, Aleksandar and Lim, Unhee and Cheng, Iona and Schumacher, Fred and Wilkens, Lynne and Li, Rongling and Monda, Keri and Ehret, Georg and Nguyen, Khanh-Dung H and Cooper, Richard and Lewis, Cora E and Leppert, Mark and Irvin, Marguerite R and Gu, C Charles and Houston, Denise and B{\r u}zkov{\'a}, Petra and Ritchie, Marylyn and Matise, Tara C and Le Marchand, Lo{\"\i}c and Hindorff, Lucia A and Crawford, Dana C and Haiman, Christopher A and Kooperberg, Charles} } @article {6687, title = {Dietary fatty acids modulate associations between genetic variants and circulating fatty acids in plasma and erythrocyte membranes: Meta-analysis of nine studies in the CHARGE consortium.}, journal = {Mol Nutr Food Res}, volume = {59}, year = {2015}, month = {2015 Jul}, pages = {1373-83}, abstract = {

SCOPE: Tissue concentrations of omega-3 fatty acids may reduce cardiovascular disease risk, and genetic variants are associated with circulating fatty acids concentrations. Whether dietary fatty acids interact with genetic variants to modify circulating omega-3 fatty acids is unclear. We evaluated interactions between genetic variants and fatty acid intakes for circulating alpha-linoleic acid, eicosapentaenoic acid, docosahexaenoic acid, and docosapentaenoic acid.

METHODS AND RESULTS: We conducted meta-analyses (N = 11~668) evaluating interactions between dietary fatty acids and genetic variants (rs174538 and rs174548 in FADS1 (fatty acid desaturase 1), rs7435 in AGPAT3 (1-acyl-sn-glycerol-3-phosphate), rs4985167 in PDXDC1 (pyridoxal-dependent decarboxylase domain-containing 1), rs780094 in GCKR (glucokinase regulatory protein), and rs3734398 in ELOVL2 (fatty acid elongase 2)). Stratification by measurement compartment (plasma versus erthyrocyte) revealed compartment-specific interactions between FADS1 rs174538 and rs174548 and dietary alpha-linolenic acid and linoleic acid for docosahexaenoic acid and docosapentaenoic acid.

CONCLUSION: Our findings reinforce earlier reports that genetically based differences in circulating fatty acids may be partially due to differences in the conversion of fatty acid precursors. Further, fatty acids measurement compartment may modify gene-diet relationships, and considering compartment may improve the detection of gene-fatty acids interactions for circulating fatty acid outcomes.

}, keywords = {Acetyltransferases, Acyltransferases, Adaptor Proteins, Signal Transducing, Carboxy-Lyases, Diet, Docosahexaenoic Acids, Eicosapentaenoic Acid, Erythrocyte Membrane, Fatty Acid Desaturases, Fatty Acids, Fatty Acids, Omega-3, Female, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide}, issn = {1613-4133}, doi = {10.1002/mnfr.201400734}, author = {Smith, Caren E and Follis, Jack L and Nettleton, Jennifer A and Foy, Millennia and Wu, Jason H Y and Ma, Yiyi and Tanaka, Toshiko and Manichakul, Ani W and Wu, Hongyu and Chu, Audrey Y and Steffen, Lyn M and Fornage, Myriam and Mozaffarian, Dariush and Kabagambe, Edmond K and Ferruci, Luigi and Chen, Yii-Der Ida and Rich, Stephen S and Djouss{\'e}, Luc and Ridker, Paul M and Tang, Weihong and McKnight, Barbara and Tsai, Michael Y and Bandinelli, Stefania and Rotter, Jerome I and Hu, Frank B and Chasman, Daniel I and Psaty, Bruce M and Arnett, Donna K and King, Irena B and Sun, Qi and Wang, Lu and Lumley, Thomas and Chiuve, Stephanie E and Siscovick, David S and Ordovas, Jose M and Lemaitre, Rozenn N} } @article {6606, title = {Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption.}, journal = {Mol Psychiatry}, volume = {20}, year = {2015}, month = {2015 May}, pages = {647-56}, abstract = {

Coffee, a major dietary source of caffeine, is among the most widely consumed beverages in the world and has received considerable attention regarding health risks and benefits. We conducted a genome-wide (GW) meta-analysis of predominately regular-type coffee consumption (cups per day) among up to 91,462 coffee consumers of European ancestry with top single-nucleotide polymorphisms (SNPs) followed-up in ~30 062 and 7964 coffee consumers of European and African-American ancestry, respectively. Studies from both stages were combined in a trans-ethnic meta-analysis. Confirmed loci were examined for putative functional and biological relevance. Eight loci, including six novel loci, met GW significance (log10Bayes factor (BF)>5.64) with per-allele effect sizes of 0.03-0.14 cups per day. Six are located in or near genes potentially involved in pharmacokinetics (ABCG2, AHR, POR and CYP1A2) and pharmacodynamics (BDNF and SLC6A4) of caffeine. Two map to GCKR and MLXIPL genes related to metabolic traits but lacking known roles in coffee consumption. Enhancer and promoter histone marks populate the regions of many confirmed loci and several potential regulatory SNPs are highly correlated with the lead SNP of each. SNP alleles near GCKR, MLXIPL, BDNF and CYP1A2 that were associated with higher coffee consumption have previously been associated with smoking initiation, higher adiposity and fasting insulin and glucose but lower blood pressure and favorable lipid, inflammatory and liver enzyme profiles (P<5 {\texttimes} 10(-8)).Our genetic findings among European and African-American adults reinforce the role of caffeine in mediating habitual coffee consumption and may point to molecular mechanisms underlying inter-individual variability in pharmacological and health effects of coffee.

}, keywords = {Adaptor Proteins, Signal Transducing, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Brain-Derived Neurotrophic Factor, Coffea, Cytochrome P-450 CYP1A2, Food Habits, Genome-Wide Association Study, Humans, Phenotype, Polymorphism, Single Nucleotide}, issn = {1476-5578}, doi = {10.1038/mp.2014.107}, author = {Cornelis, M C and Byrne, E M and Esko, T and Nalls, M A and Ganna, A and Paynter, N and Monda, K L and Amin, N and Fischer, K and Renstrom, F and Ngwa, J S and Huikari, V and Cavadino, A and Nolte, I M and Teumer, A and Yu, K and Marques-Vidal, P and Rawal, R and Manichaikul, A and Wojczynski, M K and Vink, J M and Zhao, J H and Burlutsky, G and Lahti, J and Mikkil{\"a}, V and Lemaitre, R N and Eriksson, J and Musani, S K and Tanaka, T and Geller, F and Luan, J and Hui, J and M{\"a}gi, R and Dimitriou, M and Garcia, M E and Ho, W-K and Wright, M J and Rose, L M and Magnusson, P K E and Pedersen, N L and Couper, D and Oostra, B A and Hofman, A and Ikram, M A and Tiemeier, H W and Uitterlinden, A G and van Rooij, F J A and Barroso, I and Johansson, I and Xue, L and Kaakinen, M and Milani, L and Power, C and Snieder, H and Stolk, R P and Baumeister, S E and Biffar, R and Gu, F and Bastardot, F and Kutalik, Z and Jacobs, D R and Forouhi, N G and Mihailov, E and Lind, L and Lindgren, C and Micha{\"e}lsson, K and Morris, A and Jensen, M and Khaw, K-T and Luben, R N and Wang, J J and M{\"a}nnist{\"o}, S and Per{\"a}l{\"a}, M-M and K{\"a}h{\"o}nen, M and Lehtim{\"a}ki, T and Viikari, J and Mozaffarian, D and Mukamal, K and Psaty, B M and D{\"o}ring, A and Heath, A C and Montgomery, G W and Dahmen, N and Carithers, T and Tucker, K L and Ferrucci, L and Boyd, H A and Melbye, M and Treur, J L and Mellstr{\"o}m, D and Hottenga, J J and Prokopenko, I and T{\"o}njes, A and Deloukas, P and Kanoni, S and Lorentzon, M and Houston, D K and Liu, Y and Danesh, J and Rasheed, A and Mason, M A and Zonderman, A B and Franke, L and Kristal, B S and Karjalainen, J and Reed, D R and Westra, H-J and Evans, M K and Saleheen, D and Harris, T B and Dedoussis, G and Curhan, G and Stumvoll, M and Beilby, J and Pasquale, L R and Feenstra, B and Bandinelli, S and Ordov{\'a}s, J M and Chan, A T and Peters, U and Ohlsson, C and Gieger, C and Martin, N G and Waldenberger, M and Siscovick, D S and Raitakari, O and Eriksson, J G and Mitchell, P and Hunter, D J and Kraft, P and Rimm, E B and Boomsma, D I and Borecki, I B and Loos, R J F and Wareham, N J and Vollenweider, P and Caporaso, N and Grabe, H J and Neuhouser, M L and Wolffenbuttel, B H R and Hu, F B and Hypponen, E and J{\"a}rvelin, M-R and Cupples, L A and Franks, P W and Ridker, P M and van Duijn, C M and Heiss, G and Metspalu, A and North, K E and Ingelsson, E and Nettleton, J A and van Dam, R M and Chasman, D I} } @article {7604, title = {Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram.}, journal = {Hum Mol Genet}, volume = {25}, year = {2016}, month = {2016 05 15}, pages = {2093-2103}, abstract = {

The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up.

}, keywords = {Adaptor Proteins, Signal Transducing, Arrhythmias, Cardiac, Basic Helix-Loop-Helix Transcription Factors, Brugada Syndrome, Cardiac Conduction System Disease, Death, Sudden, Cardiac, Electrocardiography, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Heart Conduction System, Humans, Male, NAV1.5 Voltage-Gated Sodium Channel, Polymorphism, Single Nucleotide, Repressor Proteins, Shab Potassium Channels, Shal Potassium Channels}, issn = {1460-2083}, doi = {10.1093/hmg/ddw058}, author = {Verweij, Niek and Mateo Leach, Irene and Isaacs, Aaron and Arking, Dan E and Bis, Joshua C and Pers, Tune H and van den Berg, Marten E and Lyytik{\"a}inen, Leo-Pekka and Barnett, Phil and Wang, Xinchen and Soliman, Elsayed Z and van Duijn, Cornelia M and K{\"a}h{\"o}nen, Mika and van Veldhuisen, Dirk J and Kors, Jan A and Raitakari, Olli T and Silva, Claudia T and Lehtim{\"a}ki, Terho and Hillege, Hans L and Hirschhorn, Joel N and Boyer, Laurie A and van Gilst, Wiek H and Alonso, Alvaro and Sotoodehnia, Nona and Eijgelsheim, Mark and de Boer, Rudolf A and de Bakker, Paul I W and Franke, Lude and van der Harst, Pim} } @article {7587, title = {Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer{\textquoteright}s disease.}, journal = {Nat Genet}, volume = {49}, year = {2017}, month = {2017 Sep}, pages = {1373-1384}, abstract = {

We identified rare coding variants associated with Alzheimer{\textquoteright}s disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 {\texttimes} 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 {\texttimes} 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer{\textquoteright}s disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 {\texttimes} 10-10, odds ratio (OR) = 0.68, minor allele frequency (MAF)cases = 0.0059, MAFcontrols = 0.0093), a risk variant in ABI3 (rs616338: p.Ser209Phe, P = 4.56 {\texttimes} 10-10, OR = 1.43, MAFcases = 0.011, MAFcontrols = 0.008), and a new genome-wide significant variant in TREM2 (rs143332484: p.Arg62His, P = 1.55 {\texttimes} 10-14, OR = 1.67, MAFcases = 0.0143, MAFcontrols = 0.0089), a known susceptibility gene for Alzheimer{\textquoteright}s disease. These protein-altering changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified risk genes in Alzheimer{\textquoteright}s disease. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to the development of Alzheimer{\textquoteright}s disease.

}, keywords = {Adaptor Proteins, Signal Transducing, Alzheimer Disease, Amino Acid Sequence, Case-Control Studies, Exome, Gene Expression Profiling, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Immunity, Innate, Linkage Disequilibrium, Membrane Glycoproteins, Microglia, Odds Ratio, Phospholipase C gamma, Polymorphism, Single Nucleotide, Protein Interaction Maps, Receptors, Immunologic, Sequence Homology, Amino Acid}, issn = {1546-1718}, doi = {10.1038/ng.3916}, author = {Sims, Rebecca and van der Lee, Sven J and Naj, Adam C and Bellenguez, C{\'e}line and Badarinarayan, Nandini and Jakobsdottir, Johanna and Kunkle, Brian W and Boland, Anne and Raybould, Rachel and Bis, Joshua C and Martin, Eden R and Grenier-Boley, Benjamin and Heilmann-Heimbach, Stefanie and Chouraki, Vincent and Kuzma, Amanda B and Sleegers, Kristel and Vronskaya, Maria and Ruiz, Agustin and Graham, Robert R and Olaso, Robert and Hoffmann, Per and Grove, Megan L and Vardarajan, Badri N and Hiltunen, Mikko and N{\"o}then, Markus M and White, Charles C and Hamilton-Nelson, Kara L and Epelbaum, Jacques and Maier, Wolfgang and Choi, Seung-Hoan and Beecham, Gary W and Dulary, C{\'e}cile and Herms, Stefan and Smith, Albert V and Funk, Cory C and Derbois, C{\'e}line and Forstner, Andreas J and Ahmad, Shahzad and Li, Hongdong and Bacq, Delphine and Harold, Denise and Satizabal, Claudia L and Valladares, Otto and Squassina, Alessio and Thomas, Rhodri and Brody, Jennifer A and Qu, Liming and S{\'a}nchez-Juan, Pascual and Morgan, Taniesha and Wolters, Frank J and Zhao, Yi and Garcia, Florentino Sanchez and Denning, Nicola and Fornage, Myriam and Malamon, John and Naranjo, Maria Candida Deniz and Majounie, Elisa and Mosley, Thomas H and Dombroski, Beth and Wallon, David and Lupton, Michelle K and Dupuis, Jos{\'e}e and Whitehead, Patrice and Fratiglioni, Laura and Medway, Christopher and Jian, Xueqiu and Mukherjee, Shubhabrata and Keller, Lina and Brown, Kristelle and Lin, Honghuang and Cantwell, Laura B and Panza, Francesco and McGuinness, Bernadette and Moreno-Grau, Sonia and Burgess, Jeremy D and Solfrizzi, Vincenzo and Proitsi, Petra and Adams, Hieab H and Allen, Mariet and Seripa, Davide and Pastor, Pau and Cupples, L Adrienne and Price, Nathan D and Hannequin, Didier and Frank-Garc{\'\i}a, Ana and Levy, Daniel and Chakrabarty, Paramita and Caffarra, Paolo and Giegling, Ina and Beiser, Alexa S and Giedraitis, Vilmantas and Hampel, Harald and Garcia, Melissa E and Wang, Xue and Lannfelt, Lars and Mecocci, Patrizia and Eiriksdottir, Gudny and Crane, Paul K and Pasquier, Florence and Boccardi, Virginia and Hen{\'a}ndez, Isabel and Barber, Robert C and Scherer, Martin and Tarraga, Lluis and Adams, Perrie M and Leber, Markus and Chen, Yuning and Albert, Marilyn S and Riedel-Heller, Steffi and Emilsson, Valur and Beekly, Duane and Braae, Anne and Schmidt, Reinhold and Blacker, Deborah and Masullo, Carlo and Schmidt, Helena and Doody, Rachelle S and Spalletta, Gianfranco and Jr, W T Longstreth and Fairchild, Thomas J and Boss{\`u}, Paola and Lopez, Oscar L and Frosch, Matthew P and Sacchinelli, Eleonora and Ghetti, Bernardino and Yang, Qiong and Huebinger, Ryan M and Jessen, Frank and Li, Shuo and Kamboh, M Ilyas and Morris, John and Sotolongo-Grau, Oscar and Katz, Mindy J and Corcoran, Chris and Dunstan, Melanie and Braddel, Amy and Thomas, Charlene and Meggy, Alun and Marshall, Rachel and Gerrish, Amy and Chapman, Jade and Aguilar, Miquel and Taylor, Sarah and Hill, Matt and Fair{\'e}n, M{\`o}nica D{\'\i}ez and Hodges, Angela and Vellas, Bruno and Soininen, Hilkka and Kloszewska, Iwona and Daniilidou, Makrina and Uphill, James and Patel, Yogen and Hughes, Joseph T and Lord, Jenny and Turton, James and Hartmann, Annette M and Cecchetti, Roberta and Fenoglio, Chiara and Serpente, Maria and Arcaro, Marina and Caltagirone, Carlo and Orfei, Maria Donata and Ciaramella, Antonio and Pichler, Sabrina and Mayhaus, Manuel and Gu, Wei and Lleo, Alberto and Fortea, Juan and Blesa, Rafael and Barber, Imelda S and Brookes, Keeley and Cupidi, Chiara and Maletta, Raffaele Giovanni and Carrell, David and Sorbi, Sandro and Moebus, Susanne and Urbano, Maria and Pilotto, Alberto and Kornhuber, Johannes and Bosco, Paolo and Todd, Stephen and Craig, David and Johnston, Janet and Gill, Michael and Lawlor, Brian and Lynch, Aoibhinn and Fox, Nick C and Hardy, John and Albin, Roger L and Apostolova, Liana G and Arnold, Steven E and Asthana, Sanjay and Atwood, Craig S and Baldwin, Clinton T and Barnes, Lisa L and Barral, Sandra and Beach, Thomas G and Becker, James T and Bigio, Eileen H and Bird, Thomas D and Boeve, Bradley F and Bowen, James D and Boxer, Adam and Burke, James R and Burns, Jeffrey M and Buxbaum, Joseph D and Cairns, Nigel J and Cao, Chuanhai and Carlson, Chris S and Carlsson, Cynthia M and Carney, Regina M and Carrasquillo, Minerva M and Carroll, Steven L and Diaz, Carolina Ceballos and Chui, Helena C and Clark, David G and Cribbs, David H and Crocco, Elizabeth A and DeCarli, Charles and Dick, Malcolm and Duara, Ranjan and Evans, Denis A and Faber, Kelley M and Fallon, Kenneth B and Fardo, David W and Farlow, Martin R and Ferris, Steven and Foroud, Tatiana M and Galasko, Douglas R and Gearing, Marla and Geschwind, Daniel H and Gilbert, John R and Graff-Radford, Neill R and Green, Robert C and Growdon, John H and Hamilton, Ronald L and Harrell, Lindy E and Honig, Lawrence S and Huentelman, Matthew J and Hulette, Christine M and Hyman, Bradley T and Jarvik, Gail P and Abner, Erin and Jin, Lee-Way and Jun, Gyungah and Karydas, Anna and Kaye, Jeffrey A and Kim, Ronald and Kowall, Neil W and Kramer, Joel H and LaFerla, Frank M and Lah, James J and Leverenz, James B and Levey, Allan I and Li, Ge and Lieberman, Andrew P and Lunetta, Kathryn L and Lyketsos, Constantine G and Marson, Daniel C and Martiniuk, Frank and Mash, Deborah C and Masliah, Eliezer and McCormick, Wayne C and McCurry, Susan M and McDavid, Andrew N and McKee, Ann C and Mesulam, Marsel and Miller, Bruce L and Miller, Carol A and Miller, Joshua W and Morris, John C and Murrell, Jill R and Myers, Amanda J and O{\textquoteright}Bryant, Sid and Olichney, John M and Pankratz, Vernon S and Parisi, Joseph E and Paulson, Henry L and Perry, William and Peskind, Elaine and Pierce, Aimee and Poon, Wayne W and Potter, Huntington and Quinn, Joseph F and Raj, Ashok and Raskind, Murray and Reisberg, Barry and Reitz, Christiane and Ringman, John M and Roberson, Erik D and Rogaeva, Ekaterina and Rosen, Howard J and Rosenberg, Roger N and Sager, Mark A and Saykin, Andrew J and Schneider, Julie A and Schneider, Lon S and Seeley, William W and Smith, Amanda G and Sonnen, Joshua A and Spina, Salvatore and Stern, Robert A and Swerdlow, Russell H and Tanzi, Rudolph E and Thornton-Wells, Tricia A and Trojanowski, John Q and Troncoso, Juan C and Van Deerlin, Vivianna M and Van Eldik, Linda J and Vinters, Harry V and Vonsattel, Jean Paul and Weintraub, Sandra and Welsh-Bohmer, Kathleen A and Wilhelmsen, Kirk C and Williamson, Jennifer and Wingo, Thomas S and Woltjer, Randall L and Wright, Clinton B and Yu, Chang-En and Yu, Lei and Garzia, Fabienne and Golamaully, Feroze and Septier, Gislain and Engelborghs, Sebastien and Vandenberghe, Rik and De Deyn, Peter P and Fernadez, Carmen Mu{\~n}oz and Benito, Yoland Aladro and Thonberg, H{\r a}kan and Forsell, Charlotte and Lilius, Lena and Kinhult-St{\r a}hlbom, Anne and Kilander, Lena and Brundin, RoseMarie and Concari, Letizia and Helisalmi, Seppo and Koivisto, Anne Maria and Haapasalo, Annakaisa and Dermecourt, Vincent and Fi{\'e}vet, Nathalie and Hanon, Olivier and Dufouil, Carole and Brice, Alexis and Ritchie, Karen and Dubois, Bruno and Himali, Jayanadra J and Keene, C Dirk and Tschanz, JoAnn and Fitzpatrick, Annette L and Kukull, Walter A and Norton, Maria and Aspelund, Thor and Larson, Eric B and Munger, Ron and Rotter, Jerome I and Lipton, Richard B and Bullido, Mar{\'\i}a J and Hofman, Albert and Montine, Thomas J and Coto, Eliecer and Boerwinkle, Eric and Petersen, Ronald C and Alvarez, Victoria and Rivadeneira, Fernando and Reiman, Eric M and Gallo, Maura and O{\textquoteright}Donnell, Christopher J and Reisch, Joan S and Bruni, Amalia Cecilia and Royall, Donald R and Dichgans, Martin and Sano, Mary and Galimberti, Daniela and St George-Hyslop, Peter and Scarpini, Elio and Tsuang, Debby W and Mancuso, Michelangelo and Bonuccelli, Ubaldo and Winslow, Ashley R and Daniele, Antonio and Wu, Chuang-Kuo and Peters, Oliver and Nacmias, Benedetta and Riemenschneider, Matthias and Heun, Reinhard and Brayne, Carol and Rubinsztein, David C and Bras, Jose and Guerreiro, Rita and Al-Chalabi, Ammar and Shaw, Christopher E and Collinge, John and Mann, David and Tsolaki, Magda and Clarimon, Jordi and Sussams, Rebecca and Lovestone, Simon and O{\textquoteright}Donovan, Michael C and Owen, Michael J and Behrens, Timothy W and Mead, Simon and Goate, Alison M and Uitterlinden, Andr{\'e} G and Holmes, Clive and Cruchaga, Carlos and Ingelsson, Martin and Bennett, David A and Powell, John and Golde, Todd E and Graff, Caroline and De Jager, Philip L and Morgan, Kevin and Ertekin-Taner, Nilufer and Combarros, Onofre and Psaty, Bruce M and Passmore, Peter and Younkin, Steven G and Berr, Claudine and Gudnason, Vilmundur and Rujescu, Dan and Dickson, Dennis W and Dartigues, Jean-Fran{\c c}ois and DeStefano, Anita L and Ortega-Cubero, Sara and Hakonarson, Hakon and Campion, Dominique and Boada, Merce and Kauwe, John Keoni and Farrer, Lindsay A and Van Broeckhoven, Christine and Ikram, M Arfan and Jones, Lesley and Haines, Jonathan L and Tzourio, Christophe and Launer, Lenore J and Escott-Price, Valentina and Mayeux, Richard and Deleuze, Jean-Francois and Amin, Najaf and Holmans, Peter A and Pericak-Vance, Margaret A and Amouyel, Philippe and van Duijn, Cornelia M and Ramirez, Alfredo and Wang, Li-San and Lambert, Jean-Charles and Seshadri, Sudha and Williams, Julie and Schellenberg, Gerard D} } @article {8375, title = {Protein and glycomic plasma markers for early detection of adenoma and colon cancer.}, journal = {Gut}, volume = {67}, year = {2018}, month = {2018 03}, pages = {473-484}, abstract = {

OBJECTIVE: To discover and confirm blood-based colon cancer early-detection markers.

DESIGN: We created a high-density antibody microarray to detect differences in protein levels in plasma from individuals diagnosed with colon cancer <3 years after blood was drawn (ie, prediagnostic) and cancer-free, matched controls. Potential markers were tested on plasma samples from people diagnosed with adenoma or cancer, compared with controls. Components of an optimal 5-marker panel were tested via immunoblotting using a third sample set, Luminex assay in a large fourth sample set and immunohistochemistry (IHC) on tissue microarrays.

RESULTS: In the prediagnostic samples, we found 78 significantly (t-test) increased proteins, 32 of which were confirmed in the diagnostic samples. From these 32, optimal 4-marker panels of BAG family molecular chaperone regulator 4 (BAG4), interleukin-6 receptor subunit beta (IL6ST), von Willebrand factor (VWF) and CD44 or epidermal growth factor receptor (EGFR) were established. Each panel member and the panels also showed increases in the diagnostic adenoma and cancer samples in independent third and fourth sample sets via immunoblot and Luminex, respectively. IHC results showed increased levels of BAG4, IL6ST and CD44 in adenoma and cancer tissues. Inclusion of EGFR and CD44 sialyl Lewis-A and Lewis-X content increased the panel performance. The protein/glycoprotein panel was statistically significantly higher in colon cancer samples, characterised by a range of area under the curves from 0.90 (95\% CI 0.82 to 0.98) to 0.86 (95\% CI 0.83 to 0.88), for the larger second and fourth sets, respectively.

CONCLUSIONS: A panel including BAG4, IL6ST, VWF, EGFR and CD44 protein/glycomics performed well for detection of early stages of colon cancer and should be further examined in larger studies.

}, keywords = {Adaptor Proteins, Signal Transducing, Adenoma, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, CA-19-9 Antigen, Case-Control Studies, Colonic Neoplasms, Cytokine Receptor gp130, Early Detection of Cancer, ErbB Receptors, Female, Humans, Hyaluronan Receptors, Lewis X Antigen, Male, Middle Aged, Oligosaccharides, Protein Array Analysis, von Willebrand Factor}, issn = {1468-3288}, doi = {10.1136/gutjnl-2016-312794}, author = {Rho, Jung-Hyun and Ladd, Jon J and Li, Christopher I and Potter, John D and Zhang, Yuzheng and Shelley, David and Shibata, David and Coppola, Domenico and Yamada, Hiroyuki and Toyoda, Hidenori and Tada, Toshifumi and Kumada, Takashi and Brenner, Dean E and Hanash, Samir M and Lampe, Paul D} }