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4. Research on Automated Fiber Placement Surface Defect Detection Based on Improved YOLOv7.

Author

Wen, Liwei, Li, Shihao, Dong, Zhentao, Shen, Haiqing, and Xu, Entao

Subjects
SURFACE defects, CARBON fibers, FIBERS, FALSE alarms, IDENTIFICATION, FEATURE extraction, DEEP learning
Abstract

Due to the black and glossy appearance of the carbon fiber prepreg bundle surface, the accurate identification of surface defects in automated fiber placement (AFP) presents a high level of difficulty. Currently, the enhanced YOLOv7 algorithm demonstrates certain performance advantages in this detection task, yet issues with missed detections, false alarms, and low confidence levels persist. Therefore, this study proposes an improved YOLOv7 algorithm to further enhance the performance and generalization of surface defect detection in AFP. Firstly, to enhance the model's feature extraction capability, the BiFormer attention mechanism is introduced to make the model pay more attention to small target defects, thereby improving feature discriminability. Next, the AFPN structure is used to replace the PAFPN at the neck layer to strengthen feature fusion, preserve semantic information to a greater extent, and finely integrate multi-scale features. Finally, WIoU is adopted to replace CIoU as the bounding box regression loss function, making it more sensitive to small targets, enabling more accurate prediction of object bounding boxes, and enhancing the model's detection accuracy and generalization capability. Through a series of ablation experiments, the improved YOLOv7 shows a 10.5% increase in mAP and a 14 FPS increase in frame rate, with a maximum detection speed of 35 m/min during the AFP process, meeting the requirements of online detection and thus being able to be applied to surface defect detection in AFP operations. [ABSTRACT FROM AUTHOR]

Published
2024
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5. FRACTURE ANALYSIS AND IMPROVEMENT OF EGR COOLER WITH ECCENTRIC INTAKE STRUCTURE

Author

HONG Yang, ZHENG ShiQian, SHEN HaiQing, and ZHAO GuoJiang

Subjects
Sequential fluid-solid coupling, Eccentric intake structure, Fracture analysis, EGR cooler, Mechanical engineering and machinery, TJ1-1570, Materials of engineering and construction. Mechanics of materials, TA401-492
Abstract

Aiming at welding fracture problem of EGR cooler with eccentric intake structure,numerical simulation based on sequential fluid-solid coupling was presented and the improvement of eccentric intake structure was taken. Flow field mesh and solid finite element mesh were set up based on 3 D modeling. The sequential fluid-solid coupling with flow field analysis,heat conduction analysis and thermal stress analysis was taken to study the relation among intake structure,gas side streamline,solid temperature,thermal stress range and the fracture. An improvement scheme with increasing a hump was proposed to improve gas uniformity and reduce local thermal stress range. The results indicate that the sequential fluid-solid coupling is feasible in engineering practice,the partial fracture of EGR cooler will caused by unreasonable eccentric intake structure and will be solved by optimization of flow passage.

Published
2021
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8. Loci influencing blood pressure identified using a cardiovascular gene-centric array

Author

Ganesh, Santhi K, Tragante, Vinicius, Guo, Wei, Guo, Yiran, Lanktree, Matthew B, Smith, Erin N, Johnson, Toby, Castillo, Berta Almoguera, Barnard, John, Baumert, Jens, Chang, Yen-Pei Christy, Elbers, Clara C, Farrall, Martin, Fischer, Mary E, Franceschini, Nora, Gaunt, Tom R, Gho, Johannes MIH, Gieger, Christian, Gong, Yan, Isaacs, Aaron, Kleber, Marcus E, Leach, Irene Mateo, McDonough, Caitrin W, Meijs, Matthijs FL, Mellander, Olle, Molony, Cliona M, Nolte, Ilja M, Padmanabhan, Sandosh, Price, Tom S, Rajagopalan, Ramakrishnan, Shaffer, Jonathan, Shah, Sonia, Shen, Haiqing, Soranzo, Nicole, van der Most, Peter J, Van Iperen, Erik PA, Van Setten, Jessic A, Vonk, Judith M, Zhang, Li, Beitelshees, Amber L, Berenson, Gerald S, Bhatt, Deepak L, Boer, Jolanda MA, Boerwinkle, Eric, Burkley, Ben, Burt, Amber, Chakravarti, Aravinda, Chen, Wei, Cooper-DeHoff, Rhonda M, Curtis, Sean P, Dreisbach, Albert, Duggan, David, Ehret, Georg B, Fabsitz, Richard R, Fornage, Myriam, Fox, Ervin, Furlong, Clement E, Gansevoort, Ron T, Hofker, Marten H, Hovingh, G Kees, Kirkland, Susan A, Kottke-Marchant, Kandice, Kutlar, Abdullah, LaCroix, Andrea Z, Langaee, Taimour Y, Li, Yun R, Lin, Honghuang, Liu, Kiang, Maiwald, Steffi, Malik, Rainer, Murugesan, Gurunathan, Newton-Cheh, Christopher, O'Connell, Jeffery R, Onland-Moret, N Charlotte, Ouwehand, Willem H, Palmas, Walter, Penninx, Brenda W, Pepine, Carl J, Pettinger, Mary, Polak, Joseph F, Ramachandran, Vasan S, Ranchalis, Jane, Redline, Susan, Ridker, Paul M, Rose, Lynda M, Scharnag, Hubert, Schork, Nicholas J, Shimbo, Daichi, Shuldiner, Alan R, Srinivasan, Sathanur R, Stolk, Ronald P, Taylor, Herman A, Thorand, Barbara, Trip, Mieke D, van Duijn, Cornelia M, Verschuren, W Monique, Wijmenga, Cisca, Winkelmann, Bernhard R, Wyatt, Sharon, and Young, J Hunter

Subjects
Hypertension, Heart Disease, Human Genome, Genetics, Clinical Research, Cardiovascular, Aetiology, 2.1 Biological and endogenous factors, Adult, Aged, Blood Pressure, Cardiovascular Diseases, Chromosome Mapping, Cohort Studies, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, White People, CARDIOGRAM, METASTROKE, LifeLines Cohort Study, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

Blood pressure (BP) is a heritable determinant of risk for cardiovascular disease (CVD). To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP) and pulse pressure (PP), we genotyped ∼50 000 single-nucleotide polymorphisms (SNPs) that capture variation in ∼2100 candidate genes for cardiovascular phenotypes in 61 619 individuals of European ancestry from cohort studies in the USA and Europe. We identified novel associations between rs347591 and SBP (chromosome 3p25.3, in an intron of HRH1) and between rs2169137 and DBP (chromosome1q32.1 in an intron of MDM4) and between rs2014408 and SBP (chromosome 11p15 in an intron of SOX6), previously reported to be associated with MAP. We also confirmed 10 previously known loci associated with SBP, DBP, MAP or PP (ADRB1, ATP2B1, SH2B3/ATXN2, CSK, CYP17A1, FURIN, HFE, LSP1, MTHFR, SOX6) at array-wide significance (P < 2.4 × 10(-6)). We then replicated these associations in an independent set of 65 886 individuals of European ancestry. The findings from expression QTL (eQTL) analysis showed associations of SNPs in the MDM4 region with MDM4 expression. We did not find any evidence of association of the two novel SNPs in MDM4 and HRH1 with sequelae of high BP including coronary artery disease (CAD), left ventricular hypertrophy (LVH) or stroke. In summary, we identified two novel loci associated with BP and confirmed multiple previously reported associations. Our findings extend our understanding of genes involved in BP regulation, some of which may eventually provide new targets for therapeutic intervention.

Published
2013

9. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Author

Asselbergs, Folkert W, Guo, Yiran, van Iperen, Erik PA, Sivapalaratnam, Suthesh, Tragante, Vinicius, Lanktree, Matthew B, Lange, Leslie A, Almoguera, Berta, Appelman, Yolande E, Barnard, John, Baumert, Jens, Beitelshees, Amber L, Bhangale, Tushar R, Chen, Yii-Der Ida, Gaunt, Tom R, Gong, Yan, Hopewell, Jemma C, Johnson, Toby, Kleber, Marcus E, Langaee, Taimour Y, Li, Mingyao, Li, Yun R, Liu, Kiang, McDonough, Caitrin W, Meijs, Matthijs FL, Middelberg, Rita PS, Musunuru, Kiran, Nelson, Christopher P, O’Connell, Jeffery R, Padmanabhan, Sandosh, Pankow, James S, Pankratz, Nathan, Rafelt, Suzanne, Rajagopalan, Ramakrishnan, Romaine, Simon PR, Schork, Nicholas J, Shaffer, Jonathan, Shen, Haiqing, Smith, Erin N, Tischfield, Sam E, van der Most, Peter J, van Vliet-Ostaptchouk, Jana V, Verweij, Niek, Volcik, Kelly A, Zhang, Li, Bailey, Kent R, Bailey, Kristian M, Bauer, Florianne, Boer, Jolanda MA, Braund, Peter S, Burt, Amber, Burton, Paul R, Buxbaum, Sarah G, Chen, Wei, Cooper-DeHoff, Rhonda M, Cupples, L Adrienne, deJong, Jonas S, Delles, Christian, Duggan, David, Fornage, Myriam, Furlong, Clement E, Glazer, Nicole, Gums, John G, Hastie, Claire, Holmes, Michael V, Illig, Thomas, Kirkland, Susan A, Kivimaki, Mika, Klein, Ronald, Klein, Barbara E, Kooperberg, Charles, Kottke-Marchant, Kandice, Kumari, Meena, LaCroix, Andrea Z, Mallela, Laya, Murugesan, Gurunathan, Ordovas, Jose, Ouwehand, Willem H, Post, Wendy S, Saxena, Richa, Scharnagl, Hubert, Schreiner, Pamela J, Shah, Tina, Shields, Denis C, Shimbo, Daichi, Srinivasan, Sathanur R, Stolk, Ronald P, Swerdlow, Daniel I, Taylor, Herman A, Topol, Eric J, Toskala, Elina, van Pelt, Joost L, van Setten, Jessica, Yusuf, Salim, Whittaker, John C, Zwinderman, AH, Study, LifeLines Cohort, Anand, Sonia S, Balmforth, Anthony J, and Berenson, Gerald S

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Human Genome, Cardiovascular, Atherosclerosis, Aetiology, 2.1 Biological and endogenous factors, Cholesterol, HDL, Cholesterol, LDL, Female, Genome-Wide Association Study, Genotype, Humans, Lipids, Male, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Sex Factors, Triglycerides, White People, LifeLines Cohort Study, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.

Published
2012

10. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height

Author

Lanktree, Matthew B, Guo, Yiran, Murtaza, Muhammed, Glessner, Joseph T, Bailey, Swneke D, Onland-Moret, N Charlotte, Lettre, Guillaume, Ongen, Halit, Rajagopalan, Ramakrishnan, Johnson, Toby, Shen, Haiqing, Nelson, Christopher P, Klopp, Norman, Baumert, Jens, Padmanabhan, Sandosh, Pankratz, Nathan, Pankow, James S, Shah, Sonia, Taylor, Kira, Barnard, John, Peters, Bas J, Maloney, Cliona M, Lobmeyer, Maximilian T, Stanton, Alice, Zafarmand, M Hadi, Romaine, Simon PR, Mehta, Amar, van Iperen, Erik PA, Gong, Yan, Price, Tom S, Smith, Erin N, Kim, Cecilia E, Li, Yun R, Asselbergs, Folkert W, Atwood, Larry D, Bailey, Kristian M, Bhatt, Deepak, Bauer, Florianne, Behr, Elijah R, Bhangale, Tushar, Boer, Jolanda MA, Boehm, Bernhard O, Bradfield, Jonathan P, Brown, Morris, Braund, Peter S, Burton, Paul R, Carty, Cara, Chandrupatla, Hareesh R, Chen, Wei, Connell, John, Dalgeorgou, Chrysoula, de Boer, Anthonius, Drenos, Fotios, Elbers, Clara C, Fang, James C, Fox, Caroline S, Frackelton, Edward C, Fuchs, Barry, Furlong, Clement E, Gibson, Quince, Gieger, Christian, Goel, Anuj, Grobbee, Diederik E, Hastie, Claire, Howard, Philip J, Huang, Guan-Hua, Johnson, W Craig, Li, Qing, Kleber, Marcus E, Klein, Barbara EK, Klein, Ronald, Kooperberg, Charles, Ky, Bonnie, LaCroix, Andrea, Lanken, Paul, Lathrop, Mark, Li, Mingyao, Marshall, Vanessa, Melander, Olle, Mentch, Frank D, Meyer, Nuala J, Monda, Keri L, Montpetit, Alexandre, Murugesan, Gurunathan, Nakayama, Karen, Nondahl, Dave, Onipinla, Abiodun, Rafelt, Suzanne, Newhouse, Stephen J, Otieno, F George, Patel, Sanjey R, Putt, Mary E, Rodriguez, Santiago, Safa, Radwan N, Sawyer, Douglas B, Schreiner, Pamela J, Simpson, Claire, Sivapalaratnam, Suthesh, Srinivasan, Sathanur R, and Suver, Christine

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adult, Black or African American, Asian People, Body Height, Cardiovascular System, Female, Gene Frequency, Genetic Heterogeneity, Genetic Loci, Genome-Wide Association Study, Hispanic or Latino, Humans, Interleukin-11, Male, Polymorphism, Single Nucleotide, Smad3 Protein, White People, Hugh Watkins on behalf of PROCARDIS, Meena Kumari on behalf of the Whitehall II Study and the WHII 50K Group, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Height is a classic complex trait with common variants in a growing list of genes known to contribute to the phenotype. Using a genecentric genotyping array targeted toward cardiovascular-related loci, comprising 49,320 SNPs across approximately 2000 loci, we evaluated the association of common and uncommon SNPs with adult height in 114,223 individuals from 47 studies and six ethnicities. A total of 64 loci contained a SNP associated with height at array-wide significance (p < 2.4 × 10(-6)), with 42 loci surpassing the conventional genome-wide significance threshold (p < 5 × 10(-8)). Common variants with minor allele frequencies greater than 5% were observed to be associated with height in 37 previously reported loci. In individuals of European ancestry, uncommon SNPs in IL11 and SMAD3, which would not be genotyped with the use of standard genome-wide genotyping arrays, were strongly associated with height (p < 3 × 10(-11)). Conditional analysis within associated regions revealed five additional variants associated with height independent of lead SNPs within the locus, suggesting allelic heterogeneity. Although underpowered to replicate findings from individuals of European ancestry, the direction of effect of associated variants was largely consistent in African American, South Asian, and Hispanic populations. Overall, we show that dense coverage of genes for uncommon SNPs, coupled with large-scale meta-analysis, can successfully identify additional variants associated with a common complex trait.

Published
2011

13. Candidate Gene Association Study of Coronary Artery Calcification in Chronic Kidney Disease: Findings From the CRIC Study (Chronic Renal Insufficiency Cohort)

Author

Ferguson, Jane F., Matthews, Gregory J., Townsend, Raymond R., Raj, Dominic S., Kanetsky, Peter A., Budoff, Matthew, Fischer, Michael J., Rosas, Sylvia E., Kanthety, Radhika, Rahman, Mahboob, Master, Stephen R., Qasim, Atif, Li, Mingyao, Mehta, Nehal N., Shen, Haiqing, Mitchell, Braxton D., O'Connell, Jeffrey R., Shuldiner, Alan R., Ho, Weang Kee, Young, Robin, Rasheed, Asif, Danesh, John, He, Jiang, Kusek, John W., Ojo, Akinlolu O., Flack, John, Go, Alan S., Gadegbeku, Crystal A., Wright, Jackson T., Jr., Saleheen, Danish, Feldman, Harold I., Rader, Daniel J., Foulkes, Andrea S., and Reilly, Muredach P.

Published
2013
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15. Whole-Genome Association Study Identifies STK39 as a Hypertension Susceptibility Gene

Author

Wang, Ying, O'Connell, Jeffrey R., McArdle, Patrick F., Wade, James B., Dorff, Sarah E., Shah, Sanjiv J., Shi, Xiaolian, Pan, Lin, Rampersaud, Evadnie, Shen, Haiqing, Kim, James D., Subramanya, Arohan R., Steinle, Nanette I., Parsa, Afshin, Ober, Carole C., Welling, Paul A., Chakravarti, Aravinda, Weder, Alan B., Cooper, Richard S., Mitchell, Braxton D., Shuldiner, Alan R., Chang, Yen-Pei C., and Semenza, Gregg L.

Published
2009
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27. Baicalin protects against APEC-induced colibacillosis by regulating gut microbiota and its metabolites in Chickens

Author

Fu Bendong, Peng-Fei Yi, Lu-Yuan Peng, Zi-Xuan Gong, Shen Haiqing, Hai-Tao Shi, Ke Song, Jing-He Li, and Jiang-Ni Huang

Subjects
animal structures, biology, medicine.drug_class, Metabolite, Antibiotics, Gut flora, biology.organism_classification, medicine.disease, medicine.disease_cause, digestive system, Pharmacological action, Microbiology, chemistry.chemical_compound, chemistry, Gene expression, medicine, Dysbiosis, Baicalin, Escherichia coli
Abstract

BACKGROUND AND PURPOSE Chicken colibacillosis, caused by avian Escherichia coli (APEC), results in huge economic losses to the poultry industry. Baicalin exerts protective effects during the development of colibacillosis. In this study, we mainly explored the mechanism of this protective effects with regard to gut microbiota. EXPERIMENTAL APPROACH The chicken colibacillosis model was established by intratracheal instillation of APEC. The gut microbiota-depleted chicken model was established with broad-spectrum antibiotics. Viscera index measurement and Haematoxylin and eosin stain were applied to assess histological changes of tissues. ELISA were used to measure the cytokines and Quantitative-PCR were used to evaluate the gene expression. The gut microbiota and its metabolite were detected by 16srDNA and ultrahigh-performance liquid chromatography (LC-MS). KEY RESULTS Depletion of gut microbiota exacerbated the tissue damage and weakened the protective effects of baicalin during APEC-induced chicken colibacillosis while pretreatment of baicalin reduced these changes and inflammatory response induced by APEC. Moreover, APEC infection led to dysbiosis of gut microbiota and its metabolites. However, the pretreatment of baicalin remodeled the gut microbiota featured with increased abundance of Intestinimonas and its associated with beneficial metabolites. CONCLUSIONS Gut microbiota played a protective role in the prevention of chicken colibacillosis and the pharmacological action of baicalin. The altered specific gut bacterial and/or metabolites may be served as indicators to predict the occurrence and prognosis of chicken colibacillosis. Our findings may provide a paradigm for the mechanistic studies of compounds and aid the exploration of the mechanisms and pathways underlying the function of herbal medicines.

Published
2020

32. Is IL12B a potential genetic target for the prevention of type 1 diabetes through dietary intervention?

Author

Ordovas, Jose M., Qi, Lu, and Shen, Haiqing

Subjects
Type 1 diabetes -- Causes of, Interleukin-12 -- Research, Diet in disease -- Research, Genetic disorders -- Causes of, Food/cooking/nutrition
Abstract

Type 1 diabetes mellitus (T1D) results from decreased insulin production. Its clinical expression is the result of an array of genetic and environmental factors. The IL12B gene could be one of the loci implicated in the genetic susceptibility of T1D. Thus, this genetic predisposition could be modulated by dietary factors. However, there is no consistency among populations in relation to relevance of this locus as a candidate gene for T1D. Key Words: Type 1 diabetes mellitus, IL12B gene, genetic predisposition

Published
2002

35. Familial Defective Apolipoprotein B-100 and Increased Low-Density Lipoprotein Cholesterol and Coronary Artery Calcification in the Old Order Amish

Author

Shen, Haiqing, Damcott, Coleen M., Rampersaud, Evadnie, Pollin, Toni I., Horenstein, Richard B., McArdle, Patrick F., Peyser, Patricia A., Bielak, Lawrence F., Post, Wendy S., Chang, Yen-Pei C., Ryan, Kathleen A., Miller, Michael, Rumberger, John A., Sheedy, Patrick F., II, Shelton, John, O’Connell, Jeffrey R., Shuldiner, Alan R., and Mitchell, Braxton D.

Published
2010
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38. Variations in the G6PC2/ABCB11 genomic region are associated with fasting glucose levels

Author

Chen, Wei-Min, Erdos, Michael R., Jackson, Anne U., Saxena, Richa, Sanna, Serena, Silver, Kristi D., Timpson, Nicholas J., Hansen, Torben, Orrú, Marco, Grazia Piras, Maria, Bonnycastle, Lori L., Willer, Cristen J., Lyssenko, Valeriya, Shen, Haiqing, Kuusisto, Johanna, Ebrahim, Shah, Sestu, Natascia, Duren, William L., Spada, Maria Cristina, Stringham, Heather M., Scott, Laura J., Olla, Nazario, Swift, Amy J., Najjar, Samer, Mitchell, Braxton D., Lawlor, Debbie A., Smith, George Davey, Ben-Shlomo, Yoav, Andersen, Gitte, Borch-Johnsen, Knut, Jørgensen, Torben, Saramies, Jouko, Valle, Timo T., Buchanan, Thomas A., Shuldiner, Alan R., Lakatta, Edward, Bergman, Richard N., Uda, Manuela, Tuomilehto, Jaakko, Pedersen, Oluf, Cao, Antonio, Groop, Leif, Mohlke, Karen L., Laakso, Markku, Schlessinger, David, Collins, Francis S., Altshuler, David, Abecasis, Gonçalo R., Boehnke, Michael, Scuteri, Angelo, and Watanabe, Richard M.

Published
2008

39. The genetic response to short-term interventions affecting cardiovascular function: Rationale and design of the Heredity and Phenotype Intervention (HAPI) Heart Study

Author

Mitchell, Braxton D., McArdle, Patrick F., Shen, Haiqing, Rampersaud, Evadnie, Pollin, Toni I., Bielak, Lawrence F., Jaquish, Cashell, Douglas, Julie A., Roy-Gagnon, Marie-Hélène, Sack, Paul, Naglieri, Rosalie, Hines, Scott, Horenstein, Richard B., Chang, Yen-Pei C., Post, Wendy, Ryan, Kathleen A., Brereton, Nga Hong, Pakyz, Ruth E., Sorkin, John, Damcott, Coleen M., OʼConnell, Jeffrey R., Mangano, Charles, Corretti, Mary, Vogel, Robert, Herzog, William, Weir, Matthew R., Peyser, Patricia A., and Shuldiner, Alan R.

Published
2008

44. Gene-centric meta-analysis in 87,736 individuals of European ancestry identifies multiple blood-pressure-related loci

Author

Nora Franceschini, Yen Pei C. Chang, Susan Kirkland, Aravinda Chakravarti, Alice Stanton, Erik P A Van Iperen, Ilja M. Nolte, Jonathan A. Shaffer, Christopher P. Nelson, Aeilko H. Zwinderman, G. Kees Hovingh, Paul I.W. de Bakker, Christian Gieger, Shen Haiqing, John M. C. Connell, Xiaofeng Zhu, Patricia B. Munroe, Thomas S. Price, Eric Boerwinkle, Deepak L. Bhatt, Santhi K. Ganesh, Anna F. Dominiczak, Caitrin W. McDonough, Harold Snieder, Vinicius Tragante, Albertine J. Oldehinkel, Eoin O'Brien, Barbara E.K. Klein, Alexander P. Reiner, Mary E. Fischer, N. Charlotte Onland-Moret, Kate Witkowska, Christopher Newton-Cheh, Andrew D. Johnson, Laura Steele, Lynda M. Rose, Li Zhang, Erin N. Smith, Mark J. Caulfield, Sharon B. Wyatt, Morris Brown, Martin D. Tobin, Christian Delles, Gail P. Jarvik, Tom R. Gaunt, Hans L. Hillege, Steffi Maiwald, Nilesh J. Samani, Wolfgang Koenig, Konrad J. Karczewski, Julie A. Johnson, Brenda W.J.H. Penninx, Matthijs F.L. Meijs, Judith M. Vonk, Yvonne T. van der Schouw, Daniel I. Chasman, John Barnard, J. Hunter Young, Paul M. Ridker, Sean P. Curtis, Marten H. Hofker, Yan Gong, Jeffrey R. O'Connell, Barbara Thorand, Garret A. FitzGerald, Daichi Shimbo, Sonia Shah, Martin Farrall, Ronald P. Stolk, John G. Gums, Amber L. Beitelshees, Juan P. Casas, Pim van der Harst, Daniel Seung Kim, Peter S. Sever, André G. Uitterlinden, Michael Snyder, Brendan J. Keating, Susan Redline, Muredach P. Reilly, Michael V. Holmes, Maciej Tomaszewski, Daniel J. Rader, Sarah S. Murray, Myriam Fornage, Walter Palmas, Karina W. Davidson, Connie R. Bezzina, Gerald S. Berenson, Toby Johnson, Afshin Parsa, Cornelia M. van Duijn, Kandice Kottke-Marchant, Winfried März, Thomas Illig, W M Monique Verschuren, Aaron Isaacs, Matthew B. Lanktree, Amber A. Burt, Hugh Watkins, Daniel Levy, Hakon Hakonarson, Ramachandran S. Vasan, Johannes M.I.H. Gho, Nathan Pankratz, Sandosh Padmanabhan, Michael R. Barnes, Anuj Goel, Berta Almoguera, Xiuqing Guo, Peter J. van der Most, Ronald Klein, Mieke D. Trip, James S. Pankow, George Davey-Smith, Eric E. Schadt, Indrani Halder, Irene Mateo Leach, Meena Kumari, Claire E. Hastie, John J.P. Kastelein, Caroline O. L. Wong, Clara C. Elbers, Folkert W. Asselbergs, Wei Guo, Marcus E. Kleber, Karen J. Cruickshanks, Pieter A. Doevendans, Jane E. Ranchalis, Yun Li, Olle Melander, Jens Baumert, Ron T. Gansevoort, Rhonda M. Cooper-DeHoff, Mary Pettinger, Cisca Wijmenga, Epidemiology, Public Health, Clinical Genetics, Child and Adolescent Psychiatry / Psychology, Internal Medicine, EMGO+ - Mental Health, APH - Amsterdam Public Health, Epidemiology and Data Science, Graduate School, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Other departments, Cardiology, Psychiatry, EMGO - Mental health, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Groningen Research Institute for Asthma and COPD (GRIAC), and Vascular Ageing Programme (VAP)

Subjects
Quality Control, Candidate gene, Genotype, Systole, Population, European Continental Ancestry Group, Quantitative Trait Loci, Single-nucleotide polymorphism, Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, Biology, Quantitative trait locus, Essential hypertension, Polymorphism, Single Nucleotide, White People, Article, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Polymorphism (computer science), Diastole, Risk Factors, medicine, Genetics, Humans, Genetics(clinical), Arterial Pressure, European Continental Ancestry Group/genetics, Polymorphism, education, Genetics (clinical), 030304 developmental biology, 0303 health sciences, education.field_of_study, Computational Biology, Single Nucleotide, Computational Biology/methods, medicine.disease, 3. Good health, Europe, Genetics, Population, Blood pressure, Phenotype, Genetic Loci, Genome-Wide Association Study
Abstract

Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ∼50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10-7) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification. © 2014 The American Society of Human Genetics.

Published
2014

48. Hundreds of variants clustered in genomic loci and biological pathways affect human height

Author

Vilmundur Gudnason, Robert J. Weyant, Robert C. Kaplan, Jeffrey R. O'Connell, Panos Deloukas, Barbara McKnight, Alessandro De Grandi, Gert-Jan B. van Ommen, Eric Boerwinkle, Liming Liang, Douglas F. Levinson, Richard B. Hayes, Mark I. McCarthy, Andrew P. Morris, Joel N. Hirschhorn, Jaakko Kaprio, Nilesh J. Samani, Inke R. König, Frank B. Hu, Nicholas J. Wareham, Ozren Polasek, Michael C. Turchin, Daniel F. Gudbjartsson, Wilmar Igl, Vincent Mooser, Aki S. Havulinna, Themistocles L. Assimes, Cameron D. Palmer, Lachlan J. M. Coin, Eva Albrecht, Hana Lango Allen, Inês Barroso, Eco J. C. de Geus, H.-Erich Wichmann, Michael A. Province, Sarah H. Wild, Patricia B. Munroe, Jeanette Erdmann, Mattias Lorentzon, Michael Preuss, Nelson B. Freimer, Mika Kähönen, Tushar Bhangale, Nicole L. Glazer, Markku S. Nieminen, Andrew A. Hicks, Jonathan Tyrer, Grant W. Montgomery, Ruth J. F. Loos, Shaun Purcell, Manfred Kayser, Marjo-Riitta Järvelin, Guillaume Paré, Terho Lehtimäki, Irene Pichler, Ida Surakka, Tõnu Esko, Peter Kraft, Talin Haritunians, Juha Sinisalo, Mari Nelis, Veronique Vitart, Alan R. Sanders, Alistair S. Hall, Carlos Iribarren, Mark E. Cooper, André G. Uitterlinden, Peter Kovacs, David Schlessinger, Florian Ernst, Marja-Liisa Lokki, M. Juhani Junttila, Martin Ridderstråle, Jorma Viikari, Inga Prokopenko, Christopher J. O'Donnell, Jennie Hui, Aila Rissanen, Gonçalo R. Abecasis, Jouke-Jan Hottenga, Tomi Pastinen, Kevin B. Jacobs, Jan Smit, Kristin G. Ardlie, Niina Pellikka, Neil R. Robertson, Martina Müller, John F. Peden, Mary F. Feitosa, Thomas W. Winkler, Kari Stefansson, Jianjun Liu, Jaana Laitinen, Shen Haiqing, Martin Farrall, Nilanjan Chatterjee, Eleanor Wheeler, Tamara B. Harris, Åsa Johansson, Anders Hamsten, Elizabeth K. Speliotes, Larry D. Atwood, Valgerdur Steinthorsdottir, Elin Grundberg, Nicole Soranzo, Anna-Liisa Hartikainen, Devin Absher, Cecilia M. Lindgren, Rany M. Salem, Lorena Citterio, Karol Estrada, Sven Bergmann, Tony Kwan, Thomas Meitinger, Alan F. Wright, Richard N. Bergman, Sailaja Vedantam, Kirsi H. Pietiläinen, Lina Zgaga, Anne U. Jackson, Stefan Schreiber, Ju-Hyun Park, Nicola Glorioso, Jianxin Shi, Najaf Amin, Dale R. Nyholt, Lenore J. Launer, Heribert Schunkert, Thomas Quertermous, Mari Liis Tammesoo, Dorret I. Boomsma, Harry Campbell, Albert V. Smith, Andrew R. Wood, Caroline S. Fox, Paavo Zitting, Gabrielle Boucher, Alex N. Parker, Jennifer G. Sambrook, Joyce B. J. van Meurs, Heather M. Stringham, Marjolein J. Peters, Sekar Kathiresan, Elisabeth Widen, Caroline Hayward, Tim D. Spector, Dawn M. Waterworth, Carlo Rivolta, Antti Jula, Albert Hofman, Hugh Watkins, Wendy L. McArdle, Roberto Elosua, Markku Koiranen, Paul M. Ridker, Iris M. Heid, Lee M. Kaplan, Brenda W.J.H. Penninx, Peter M. Visscher, Claes Ohlsson, Per Hall, Benjamin F. Voight, Ben A. Oostra, Anna F. Dominiczak, Martin den Heijer, Andrea Maschio, Quince Gibson, Peter P. Pramstaller, Nigel W. Rayner, Carsten Oliver Schmidt, Toby Johnson, Henrik Grönberg, M. Carola Zillikens, Alan R. Shuldiner, Cornelia M. van Duijn, Samuli Ripatti, Erik Ingelsson, John R. Thompson, Stephen J. Chanock, Johannes Kettunen, David J. Hunter, Lyle J. Palmer, Ulf Gyllensten, Jianfeng Xu, Astrid Petersmann, Johan G. Eriksson, Guillaume Lettre, Teresa Ferreira, Fredrik Wiklund, Andreas Ziegler, Andres Metspalu, Jerome I. Rotter, Suzanne Rafelt, Julius S. Ngwa, Francis S. Collins, Michael N. Weedon, Thomas Illig, Wolfgang Hoffman, Nancy L. Heard-Costa, Anke Tönjes, Daniel I. Chasman, Alice M. Arnold, Olli T. Raitakari, Anna L. Dixon, Lu Qi, Michael E. Goddard, Anneli Pouta, Mark J. Caulfield, Liesbeth Vandenput, Christian Gieger, L. Adrienne Cupples, Veikko Salomaa, Elizabeth L. Altmaier, Nicholas G. Martin, Thomas D. Kocher, Jubao Duan, David S. Siscovick, Heikki V. Huikuri, Willem H. Ouwehand, Kari E. North, Christian Hengstenberg, Jacques S. Beckmann, Constance Chen, John Perry, Ana Marušić, Olle Melander, John D. Rioux, Erika Salvi, Andrew T. Hattersley, Paul Elliott, Leif Groop, Cristen J. Willer, Manuela Uda, Gudmar Thorleifsson, Eric E. Schadt, Charles C. White, Pablo V. Gejman, Serena Sanna, Ulla Sovio, Robert W. Lawrence, Unnur Thorsteinsdottir, Ayellet V. Segrè, Daniele Cusi, G. Bragi Walters, Ken Sin Lo, Ivana Kolcic, Igor Rudan, Sonja I. Berndt, Keri L. Monda, Soumya Raychaudhuri, Jian'an Luan, Joshua C. Randall, Anthony J. Balmforth, Yurii S. Aulchenko, Peter Almgren, Karen L. Mohlke, Timothy M. Frayling, Shamika Ketkar, Thomas H. Mosley, Markus Perola, Henry Völzke, Laura Zagato, Leena Peltonen, Seppo Koskinen, Massimo Mangino, Ke Hao, Tsegaselassie Workalemahu, Lambertus A. Kiemeney, Helene Alavere, Jaakko Tuomilehto, Reedik Mägi, James F. Wilson, Ingrid B. Borecki, Zoltán Kutalik, Michael Stumvoll, Dominique J. Verlaan, Arthur W. Musk, Eero Kajantie, Jian Yang, Joshua W. Knowles, Tuomas O. Kilpeläinen, Michael Boehnke, G. Mark Lathrop, John Beilby, Fernando Rivadeneira, Gudny Eiriksdottir, Gonneke Willemsen, Andrew C. Heath, Antonella Mulas, Katja K.H. Aben, David P. Strachan, Thor Aspelund, Jing Hua Zhao, Psychiatry, NCA - Anxiety & Depression, EMGO - Mental health, Internal Medicine, Epidemiology, Intensive Care, Clinical Genetics, Genetic Identification, Medical Research Council (MRC), Biological Psychology, Neuroscience Campus Amsterdam - Anxiety & Depression, EMGO+ - Mental Health, Genetics of Complex Traits, University of Exeter, Department of Epidemiology, Erasmus Medical Centre, Netherlands Genomics Initiative (NGI), Netherlands Genomics Initiative, Department of Medicine, Montreal, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH), Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, deCODE Genetics, deCODE genetics [Reykjavik], Divisions of Genetics and Endocrinology and Program in Genomics, Boston Children's Hospital, Metabolism Initiative and Program in Medical and Population Genetics, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston]-Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Institut de Génomique d'Evry (IG), Institut de Biologie François JACOB (JACOB), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, the Genetic Investigation of ANthropocentric Traits (GIANT) Consortium, Université Paris-Saclay-Institut de Biologie François JACOB (JACOB), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
Netherlands Twin Register (NTR), Multifactorial Inheritance, [SDV]Life Sciences [q-bio], Genome-wide association study, Aetiology, screening and detection [ONCOL 5], 0302 clinical medicine, POPULATION, SNPS, Genetics, 0303 health sciences, Multidisciplinary, HERITABILITY, COMMON VARIANTS, Phenotype, DISEASES, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Science & Technology - Other Topics, GROWTH, Allelic heterogeneity, Chromosomes, Human, Pair 3, Metabolic Networks and Pathways, TRAITS, Common disease-common variant, General Science & Technology, Locus (genetics), Biology, Polymorphism, Single Nucleotide, Article, Molecular epidemiology [NCEBP 1], 03 medical and health sciences, SDG 3 - Good Health and Well-being, ADULT, STRATIFICATION, MD Multidisciplinary, Humans, Genetic Predisposition to Disease, Genetic variability, 030304 developmental biology, Science & Technology, MULTIDISCIPLINARY SCIENCES, Genome, Human, Hormonal regulation [IGMD 6], Body Height, Genetic architecture, wide association analysis common variants heritability population adult stratification diseases traits growth snps, WIDE ASSOCIATION ANALYSIS, Genetic Loci, Evaluation of complex medical interventions [NCEBP 2], Polygene, Expression quantitative trait loci, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits1, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait2,3. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways ( P=0.016) and that underlie skeletal growth defects ( P

Published
2010

49. Meta-analysis of Dense Genecentric Association Studies Reveals Common and Uncommon Variants Associated with Height (vol 88, pg 6, 2010)

Author

Lanktree, Matthew B., Guo, Yiran, Murtaza, Muhammed, Glessner, Joseph T., Bailey, Swneke D., Onland-Moret, N. Charlotte, Lettre, Guillaume, Ongen, Halit, Rajagopalan, Ramakrishnan, Johnson, Toby, Shen, Haiqing, Nelson, Christopher P., Klopp, Norman, Baumert, Jens, Padmanabhan, Sandosh, Pankratz, Nathan, Pankow, James S., Shah, Sonia, Taylor, Kira, Barnard, John, Peters, Bas J., Maloney, Cliona M., Lobmeyer, Maximilian T., Stanton, Alice, Zafarmand, M. Hadi, Romaine, Simon P. R., Mehta, Amar, van Iperen, Erik P. A., Gong, Yan, Price, Tom S., Smith, Erin N., Kim, Cecilia E., Li, Yun R., Asselbergs, Folkert W., Atwood, Larry D., Bailey, Kristian M., Bhatt, Deepak, Bauer, Florianne, Behr, Elijah R., Bhangale, Tushar, Boer, Jolanda M. A., Boehm, Bernhard O., Bradfield, Jonathan P., Brown, Morris, Braund, Peter S., Chen, Wei, Hofker, Marten H., Wijmenga, Cisca, Kumari, Meena, Center for Liver, Digestive and Metabolic Diseases (CLDM), Vascular Ageing Programme (VAP), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)

Published
2012

50. Large-Scale Gene-Centric Meta-analysis across 32 Studies Identifies Multiple Lipid Loci

Author

Asselbergs, Folkert W., Guo, Yiran, Van Iperen, Erik P. A., Sivapalaratnam, Suthesh, Tragante, Vinicius, Lanktree, Matthew B., Lange, Leslie A., Almoguera, Berta, Appelman, Yolande E., Barnard, John, Baumert, Jens, Beitelshees, Amber L., Bhangale, Tushar R., Chen, Yii-Der Ida, Gaunt, Tom R., Gong, Yan, Hopewell, Jemma C., Johnson, Toby, Kleber, Marcus E., Langaee, Taimour Y., Li, Mingyao, Li, Yun R., Liu, Kiang, McDonough, Caitrin W., Meijs, Matthijs F. L., Middelberg, Rita P. S., Musunuru, Kiran, Nelson, Christopher P., O’Connell, Jeffrey R., Padmanabhan, Sandosh, Pankow, James S., Pankratz, Nathan, Rafelt, Suzanne, Rajagopalan, Ramakrishnan, Romaine, Simon P. R., Schork, Nicholas J., Shaffer, Jonathan, Shen, Haiqing, Smith, Erin N., Tischfield, Sam E., Van Der Most, Peter J., Van Vliet-Ostaptchouk, Jana V., Verweij, Niek, Volcik, Kelly A., Zhang, Li, Bailey, Kent R., Bailey, Kristian M., Bauer, Florianne, Boer, Jolanda M. A., Braund, Peter S., Burt, Amber, Burton, Paul R., Buxbaum, Sarah G., Chen, Wei, Cooper-DeHoff, Rhonda M., Cupples, L. Adrienne, DeJong, Jonas S., Delles, Christian, Duggan, David, Fornage, Myriam, Furlong, Clement E., Glazer, Nicole, Gums, John G., Hastie, Claire, Holmes, Michael V., Illig, Thomas, Kirkland, Susan A., Kivimaki, Mika, Klein, Ronald, Klein, Barbara E., Kooperberg, Charles, Kottke-Marchant, Kandice, Kumari, Meena, LaCroix, Andrea Z., Mallela, Laya, Murugesan, Gurunathan, Ordovas, Jose, Ouwehand, Willem H., Post, Wendy S., Saxena, Richa, Scharnagl, Hubert, Schreiner, Pamela J., Shah, Tina, Shields, Denis C., Shimbo, Daichi, Srinivasan, Sathanur R., Stolk, Ronald P., Swerdlow, Daniel I., Taylor Jr., Herman A., Topol, Eric J., Toskala, Elina, Van Pelt, Joost L., Van Setten, Jessica, Yusuf, Salim, Whittaker, John C., Zwinderman, A. H., Anand, Sonia S., Balmforth, Anthony J., Berenson, Gerald S., Bezzina, Connie R., Boehm, Bernhard O., Boerwinkle, Eric, Casas, Juan P., Caulfield, Mark J., Clarke, Robert, Connell, John M., Cruickshanks, Karen J., Davidson, Karina W., Day, Ian N. M., De Bakker, Paul I. W., Doevendans, Pieter A., Dominiczak, Anna F., Hall, Alistair S., Hartman, Catharina A., Hengstenberg, Christian, Hillege, Hans L., Hofker, Marten H., Humphries, Steve E., Jarvik, Gail P., Johnson, Julie A., Kaess, Bernhard M., Kathiresan, Sekar, Koenig, Wolfgang, Lawlor, Debbie A., Marz, Winfried, Melander, Olle, Mitchell, Braxton D., Montgomery, Grant W., Munroe, Patricia B., Murray, Sarah S., Newhouse, Stephen J., Onland-Moret, N. Charlotte, Poulter, Neil, Psaty, Bruce, Redline, Susan, Rich, Stephen S., Rotter, Jerome I., Schunkert, Heribert, Sever, Peter, Shuldiner, Alan R., Silverstein, Roy L., Stanton, Alice, Thorand, Barbara, Trip, Mieke D., Tsai, Michael Y., Van Der Harst, Pim, Van Der Schoot, Ellen, Van Der Schouw, Yvonne T., Verschuren, W. M. Monique, Watkins, Hugh, Wilde, Arthur A. M., Wolffenbuttel, Bruce H. R., Whitfield, John B., Hovingh, G. Kees, Ballantyne, Christie M., Wijmenga, Cisca, Reilly, Muredach P., Martin, Nicholas G., and LifeLines Cohort Study

Subjects
Meta-analysis, Molecular biology, FOS: Biological sciences, Genetics, nutritional and metabolic diseases, lipids (amino acids, peptides, and proteins), Single nucleotide polymorphisms, Medical sciences, Lipids
Abstract

Genome-wide association studies (GWASs) have identified many SNPs underlying variations in plasma-lipid levels. We explore whether additional loci associated with plasma-lipid phenotypes, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglycerides (TGs), can be identified by a dense gene-centric approach. Our meta-analysis of 32 studies in 66,240 individuals of European ancestry was based on the custom ∼50,000 SNP genotyping array (the ITMAT-Broad-CARe array) covering ∼2,000 candidate genes. SNP-lipid associations were replicated either in a cohort comprising an additional 24,736 samples or within the Global Lipid Genetic Consortium. We identified four, six, ten, and four unreported SNPs in established lipid genes for HDL-C, LDL-C, TC, and TGs, respectively. We also identified several lipid-related SNPs in previously unreported genes: DGAT2, HCAR2, GPIHBP1, PPARG, and FTO for HDL-C; SOCS3, APOH, SPTY2D1, BRCA2, and VLDLR for LDL-C; SOCS3, UGT1A1, BRCA2, UBE3B, FCGR2A, CHUK, and INSIG2 for TC; and SERPINF2, C4B, GCK, GATA4, INSR, and LPAL2 for TGs. The proportion of explained phenotypic variance in the subset of studies providing individual-level data was 9.9% for HDL-C, 9.5% for LDL-C, 10.3% for TC, and 8.0% for TGs. This large meta-analysis of lipid phenotypes with the use of a dense gene-centric approach identified multiple SNPs not previously described in established lipid genes and several previously unknown loci. The explained phenotypic variance from this approach was comparable to that from a meta-analysis of GWAS data, suggesting that a focused genotyping approach can further increase the understanding of heritability of plasma lipids.

Published
2012
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