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1,030 results on '"Bell, Graeme I."'

1. Multiethnic Meta-Analysis Identifies RAI1 as a Possible Obstructive Sleep Apnea–related Quantitative Trait Locus in Men

Author

Chen, Han, Cade, Brian E, Gleason, Kevin J, Bjonnes, Andrew C, Stilp, Adrienne M, Sofer, Tamar, Conomos, Matthew P, Ancoli-Israel, Sonia, Arens, Raanan, Azarbarzin, Ali, Bell, Graeme I, Below, Jennifer E, Chun, Sung, Evans, Daniel S, Ewert, Ralf, Frazier-Wood, Alexis C, Gharib, Sina A, Haba-Rubio, José, Hagen, Erika W, Heinzer, Raphael, Hillman, David R, Johnson, W Craig, Kutalik, Zoltan, Lane, Jacqueline M, Larkin, Emma K, Lee, Seung Ku, Liang, Jingjing, Loredo, Jose S, Mukherjee, Sutapa, Palmer, Lyle J, Papanicolaou, George J, Penzel, Thomas, Peppard, Paul E, Post, Wendy S, Ramos, Alberto R, Rice, Ken, Rotter, Jerome I, Sands, Scott A, Shah, Neomi A, Shin, Chol, Stone, Katie L, Stubbe, Beate, Sul, Jae Hoon, Tafti, Mehdi, Taylor, Kent D, Teumer, Alexander, Thornton, Timothy A, Tranah, Gregory J, Wang, Chaolong, Wang, Heming, Warby, Simon C, Wellman, D Andrew, Zee, Phyllis C, Hanis, Craig L, Laurie, Cathy C, Gottlieb, Daniel J, Patel, Sanjay R, Zhu, Xiaofeng, Sunyaev, Shamil R, Saxena, Richa, Lin, Xihong, and Redline, Susan

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Sleep Research, Clinical Research, Human Genome, Lung, 2.1 Biological and endogenous factors, Aetiology, Adult, Aged, Female, Genome-Wide Association Study, Humans, Male, Middle Aged, Phosphatidylethanolamine N-Methyltransferase, Quantitative Trait Loci, Sex Characteristics, Sleep Apnea, Obstructive, Sleep, REM, Sterol Regulatory Element Binding Protein 1, Trans-Activators, Transcription Factors, ras Proteins, obstructive sleep apnea, genetics, genome-wide association studies, multiethnic, sexual dimorphism, Cardiorespiratory Medicine and Haematology, Respiratory System, Biochemistry and cell biology, Cardiovascular medicine and haematology
Abstract

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.

Published
2018

2. Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees

Author

Jun, Goo, Manning, Alisa, Almeida, Marcio, Zawistowski, Matthew, Wood, Andrew R, Teslovich, Tanya M, Fuchsberger, Christian, Feng, Shuang, Cingolani, Pablo, Gaulton, Kyle J, Dyer, Thomas, Blackwell, Thomas W, Chen, Han, Chines, Peter S, Choi, Sungkyoung, Churchhouse, Claire, Fontanillas, Pierre, King, Ryan, Lee, SungYoung, Lincoln, Stephen E, Trubetskoy, Vasily, DePristo, Mark, Fingerlin, Tasha, Grossman, Robert, Grundstad, Jason, Heath, Alison, Kim, Jayoun, Kim, Young Jin, Laramie, Jason, Lee, Jaehoon, Li, Heng, Liu, Xuanyao, Livne, Oren, Locke, Adam E, Maller, Julian, Mazur, Alexander, Morris, Andrew P, Pollin, Toni I, Ragona, Derek, Reich, David, Rivas, Manuel A, Scott, Laura J, Sim, Xueling, Tearle, Rick G, Teo, Yik Ying, Williams, Amy L, Zöllner, Sebastian, Curran, Joanne E, Peralta, Juan, Akolkar, Beena, Bell, Graeme I, Burtt, Noël P, Cox, Nancy J, Florez, Jose C, Hanis, Craig L, McKeon, Catherine, Mohlke, Karen L, Seielstad, Mark, Wilson, James G, Atzmon, Gil, Below, Jennifer E, Dupuis, Josée, Nicolae, Dan L, Lehman, Donna, Park, Taesung, Won, Sungho, Sladek, Robert, Altshuler, David, McCarthy, Mark I, Duggirala, Ravindranath, Boehnke, Michael, Frayling, Timothy M, Abecasis, Gonçalo R, and Blangero, John

Subjects
Diabetes, Genetics, Human Genome, Clinical Research, Obesity, Genetic Testing, 2.1 Biological and endogenous factors, Aetiology, Metabolic and endocrine, Diabetes Mellitus, Type 2, Family Health, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Humans, Male, Mexican Americans, Pedigree, Phenotype, Quantitative Trait Loci, Whole Genome Sequencing, genetics, sequencing, type 2 diabetes, eQTL, rare variants
Abstract

A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis-expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants.

Published
2018

5. Genetic Associations with Obstructive Sleep Apnea Traits in Hispanic/Latino Americans

Author

Cade, Brian E, Chen, Han, Stilp, Adrienne M, Gleason, Kevin J, Sofer, Tamar, Ancoli-Israel, Sonia, Arens, Raanan, Bell, Graeme I, Below, Jennifer E, Bjonnes, Andrew C, Chun, Sung, Conomos, Matthew P, Evans, Daniel S, Johnson, W Craig, Frazier-Wood, Alexis C, Lane, Jacqueline M, Larkin, Emma K, Loredo, Jose S, Post, Wendy S, Ramos, Alberto R, Rice, Ken, Rotter, Jerome I, Shah, Neomi A, Stone, Katie L, Taylor, Kent D, Thornton, Timothy A, Tranah, Gregory J, Wang, Chaolong, Zee, Phyllis C, Hanis, Craig L, Sunyaev, Shamil R, Patel, Sanjay R, Laurie, Cathy C, Zhu, Xiaofeng, Saxena, Richa, Lin, Xihong, and Redline, Susan

Subjects
Genetics, Clinical Research, Lung, Aging, Prevention, Sleep Research, Human Genome, Aetiology, 2.1 Biological and endogenous factors, Good Health and Well Being, sleep apnea, hypoxia, genetics, GWAS, Prader-Willi syndrome, Prader–Willi syndrome, Medical and Health Sciences, Respiratory System
Abstract

RationaleObstructive sleep apnea is a common disorder associated with increased risk for cardiovascular disease, diabetes, and premature mortality. Although there is strong clinical and epidemiologic evidence supporting the importance of genetic factors in influencing obstructive sleep apnea, its genetic basis is still largely unknown. Prior genetic studies focused on traits defined using the apnea-hypopnea index, which contains limited information on potentially important genetically determined physiologic factors, such as propensity for hypoxemia and respiratory arousability.ObjectivesTo define novel obstructive sleep apnea genetic risk loci for obstructive sleep apnea, we conducted genome-wide association studies of quantitative traits in Hispanic/Latino Americans from three cohorts.MethodsGenome-wide data from as many as 12,558 participants in the Hispanic Community Health Study/Study of Latinos, Multi-Ethnic Study of Atherosclerosis, and Starr County Health Studies population-based cohorts were metaanalyzed for association with the apnea-hypopnea index, average oxygen saturation during sleep, and average respiratory event duration.Measurements and main resultsTwo novel loci were identified at genome-level significance (rs11691765, GPR83, P = 1.90 × 10-8 for the apnea-hypopnea index, and rs35424364; C6ORF183/CCDC162P, P = 4.88 × 10-8 for respiratory event duration) and seven additional loci were identified with suggestive significance (P

Published
2016

6. Identification and functional characterization of G6PC2 coding variants influencing glycemic traits define an effector transcript at the G6PC2-ABCB11 locus.

Author

Mahajan, Anubha, Sim, Xueling, Ng, Hui Jin, Manning, Alisa, Rivas, Manuel A, Highland, Heather M, Locke, Adam E, Grarup, Niels, Im, Hae Kyung, Cingolani, Pablo, Flannick, Jason, Fontanillas, Pierre, Fuchsberger, Christian, Gaulton, Kyle J, Teslovich, Tanya M, Rayner, N William, Robertson, Neil R, Beer, Nicola L, Rundle, Jana K, Bork-Jensen, Jette, Ladenvall, Claes, Blancher, Christine, Buck, David, Buck, Gemma, Burtt, Noël P, Gabriel, Stacey, Gjesing, Anette P, Groves, Christopher J, Hollensted, Mette, Huyghe, Jeroen R, Jackson, Anne U, Jun, Goo, Justesen, Johanne Marie, Mangino, Massimo, Murphy, Jacquelyn, Neville, Matt, Onofrio, Robert, Small, Kerrin S, Stringham, Heather M, Syvänen, Ann-Christine, Trakalo, Joseph, Abecasis, Goncalo, Bell, Graeme I, Blangero, John, Cox, Nancy J, Duggirala, Ravindranath, Hanis, Craig L, Seielstad, Mark, Wilson, James G, Christensen, Cramer, Brandslund, Ivan, Rauramaa, Rainer, Surdulescu, Gabriela L, Doney, Alex SF, Lannfelt, Lars, Linneberg, Allan, Isomaa, Bo, Tuomi, Tiinamaija, Jørgensen, Marit E, Jørgensen, Torben, Kuusisto, Johanna, Uusitupa, Matti, Salomaa, Veikko, Spector, Timothy D, Morris, Andrew D, Palmer, Colin NA, Collins, Francis S, Mohlke, Karen L, Bergman, Richard N, Ingelsson, Erik, Lind, Lars, Tuomilehto, Jaakko, Hansen, Torben, Watanabe, Richard M, Prokopenko, Inga, Dupuis, Josee, Karpe, Fredrik, Groop, Leif, Laakso, Markku, Pedersen, Oluf, Florez, Jose C, Morris, Andrew P, Altshuler, David, Meigs, James B, Boehnke, Michael, McCarthy, Mark I, Lindgren, Cecilia M, Gloyn, Anna L, and T2D-GENES consortium and GoT2D consortium

Subjects
T2D-GENES consortium and GoT2D consortium, Humans, Diabetes Mellitus, Type 2, Insulin, Glucose-6-Phosphatase, Blood Glucose, Receptors, Glucagon, Glycemic Index, Gene Frequency, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Exome, Glucagon-Like Peptide-1 Receptor, Diabetes Mellitus, Type 2, Receptors, Glucagon, Polymorphism, Single Nucleotide, Genetics, Developmental Biology
Abstract

Genome wide association studies (GWAS) for fasting glucose (FG) and insulin (FI) have identified common variant signals which explain 4.8% and 1.2% of trait variance, respectively. It is hypothesized that low-frequency and rare variants could contribute substantially to unexplained genetic variance. To test this, we analyzed exome-array data from up to 33,231 non-diabetic individuals of European ancestry. We found exome-wide significant (P

Published
2015

7. Genetic Complexity in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin

Author

Park, Soo-Young, Ludwig, Michael Z., Tamarina, Natalia A., He, Bin Z., Carl, Sarah H., Dickerson, Desiree A., Barse, Levi, Arun, Bharath, Williams, Calvin, Miles, Cecelia M., Philipson, Louis H., Steiner, Donald F., Bell, Graeme I., and Kreitman, Martin

Subjects
Quantitative Biology - Genomics, Quantitative Biology - Populations and Evolution
Abstract

Here we use Drosophila melanogaster to create a genetic model of human permanent neonatal diabetes mellitus and present experimental results describing dimensions of this complexity. The approach involves the transgenic expression of a misfolded mutant of human preproinsulin, hINSC96Y, which is a cause of the disease. When expressed in fly imaginal discs, hINSC96Y causes a reduction of adult structures, including the eye, wing and notum. Eye imaginal discs exhibit defects in both the structure and arrangement of ommatidia. In the wing, expression of hINSC96Y leads to ectopic expression of veins and mechano-sensory organs, indicating disruption of wild type signaling processes regulating cell fates. These readily measurable disease phenotypes are sensitive to temperature, gene dose and sex. Mutant (but not wild type) proinsulin expression in the eye imaginal disc induces IRE1-mediated Xbp1 alternative splicing, a signal for endoplasmic reticulum stress response activation, and produces global change in gene expression. Mutant hINS transgene tester strains, when crossed to stocks from the Drosophila Genetic Reference Panel produces F1 adults with a continuous range of disease phenotypes and large broad-sense heritability. Surprisingly, the severity of mutant hINS-induced disease in the eye is not correlated with that in the notum in these crosses, nor with eye reduction phenotypes caused by the expression of two dominant eye mutants acting in two different eye development pathways, Drop (Dr) or Lobe (L) when crossed into the same genetic backgrounds. The tissue specificity of genetic variability for mutant hINS-induced disease thus has its own distinct signature. The genetic dominance of disease-specific phenotypic variability makes this approach amenable to genome-wide association study (GWAS) in a simple F1 screen of natural variation., Comment: 60 pages; 6 figures; 8 supporting figures; 11 supporting tables

Published
2013

8. Effect of Genetic Variation in a Drosophila Model of Diabetes-Associated Misfolded Human Proinsulin

Author

He, Bin Z., Ludwig, Michael Z., Dickerson, Desiree A., Barse, Levi, Arun, Bharath, Park, Soo Young, Tamarina, Natalia A., Selleck, Scott B., Wittkopp, Patricia, Bell, Graeme I., and Kreitman, Martin

Subjects
Quantitative Biology - Populations and Evolution, Quantitative Biology - Genomics
Abstract

The identification and validation of gene-gene interactions is a major challenge in human studies. Here, we explore an approach for studying epistasis in humans using a Drosophila melanogaster model of neonatal diabetes mellitus. Expression of mutant preproinsulin, hINSC96Y, in the eye imaginal disc mimics the human disease activating conserved cell stress response pathways leading to cell death and reduction in eye area. Dominant-acting variants in wild-derived inbred lines from the Drosophila Genetics Reference Panel produce a continuous, highly heritable, distribution of eye degeneration phenotypes. A genome-wide association study (GWAS) in 154 sequenced lines identified 29 candidate SNPs in 16 loci with P < 10-5 including one SNP in an intron of the gene sulfateless (sfl) which exceeded a conservative genome-wide significance threshold of P = 0.05 level (-log10 P > 7.62). RNAi knock-downs of sfl enhanced the eye degeneration phenotype in a mutant-hINS-dependent manner. sfl encodes a protein required for sulfation of the glycosaminoglycan, heparan sulfate. Two additional genes in the heparan sulfate (HS) biosynthetic pathway (tout velu, ttv and brother of tout velu, botv) also modified the eye phenotype, suggesting a link between HS-modified proteins and cellular responses to misfolded proteins. Finally, intronic variants marking the QTL were associated with decreased sfl expression, a result consistent with that predicted by RNAi studies. The ability to create a model of human genetic disease in the fly, map a QTL by GWAS to a specific gene (and noncoding variant), validate its contribution to disease with available genetic resources, and experimentally link the variant to a molecular mechanism, demonstrate the many advantages Drosophila holds in determining the genetic underpinnings of human disease.

Published
2013
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9. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Author

Mahajan, Anubha, Go, Min Jin, Zhang, Weihua, Below, Jennifer E, Gaulton, Kyle J, Ferreira, Teresa, Horikoshi, Momoko, Johnson, Andrew D, Ng, Maggie CY, Prokopenko, Inga, Saleheen, Danish, Wang, Xu, Zeggini, Eleftheria, Abecasis, Goncalo R, Adair, Linda S, Almgren, Peter, Atalay, Mustafa, Aung, Tin, Baldassarre, Damiano, Balkau, Beverley, Bao, Yuqian, Barnett, Anthony H, Barroso, Ines, Basit, Abdul, Been, Latonya F, Beilby, John, Bell, Graeme I, Benediktsson, Rafn, Bergman, Richard N, Boehm, Bernhard O, Boerwinkle, Eric, Bonnycastle, Lori L, Burtt, Noël, Cai, Qiuyin, Campbell, Harry, Carey, Jason, Cauchi, Stephane, Caulfield, Mark, Chan, Juliana CN, Chang, Li-Ching, Chang, Tien-Jyun, Chang, Yi-Cheng, Charpentier, Guillaume, Chen, Chien-Hsiun, Chen, Han, Chen, Yuan-Tsong, Chia, Kee-Seng, Chidambaram, Manickam, Chines, Peter S, Cho, Nam H, Cho, Young Min, Chuang, Lee-Ming, Collins, Francis S, Cornelis, Marilyn C, Couper, David J, Crenshaw, Andrew T, van Dam, Rob M, Danesh, John, Das, Debashish, de Faire, Ulf, Dedoussis, George, Deloukas, Panos, Dimas, Antigone S, Dina, Christian, Doney, Alex SF, Donnelly, Peter J, Dorkhan, Mozhgan, van Duijn, Cornelia, Dupuis, Josée, Edkins, Sarah, Elliott, Paul, Emilsson, Valur, Erbel, Raimund, Eriksson, Johan G, Escobedo, Jorge, Esko, Tonu, Eury, Elodie, Florez, Jose C, Fontanillas, Pierre, Forouhi, Nita G, Forsen, Tom, Fox, Caroline, Fraser, Ross M, Frayling, Timothy M, Froguel, Philippe, Frossard, Philippe, Gao, Yutang, Gertow, Karl, Gieger, Christian, Gigante, Bruna, Grallert, Harald, Grant, George B, Groop, Leif C, Groves, Christopher J, Grundberg, Elin, Guiducci, Candace, Hamsten, Anders, Han, Bok-Ghee, Hara, Kazuo, and Hassanali, Neelam

Subjects
Biological Sciences, Genetics, Human Genome, Diabetes, Metabolic and endocrine, Alleles, Asian People, Case-Control Studies, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Genome-Wide Association Study, Hispanic or Latino, Humans, Polymorphism, Single Nucleotide, Risk Factors, White People, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Published
2014

10. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility.

Author

DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Mahajan, Anubha, Go, Min Jin, Zhang, Weihua, Below, Jennifer E, Gaulton, Kyle J, Ferreira, Teresa, Horikoshi, Momoko, Johnson, Andrew D, Ng, Maggie CY, Prokopenko, Inga, Saleheen, Danish, Wang, Xu, Zeggini, Eleftheria, Abecasis, Goncalo R, Adair, Linda S, Almgren, Peter, Atalay, Mustafa, Aung, Tin, Baldassarre, Damiano, Balkau, Beverley, Bao, Yuqian, Barnett, Anthony H, Barroso, Ines, Basit, Abdul, Been, Latonya F, Beilby, John, Bell, Graeme I, Benediktsson, Rafn, Bergman, Richard N, Boehm, Bernhard O, Boerwinkle, Eric, Bonnycastle, Lori L, Burtt, Noël, Cai, Qiuyin, Campbell, Harry, Carey, Jason, Cauchi, Stephane, Caulfield, Mark, Chan, Juliana CN, Chang, Li-Ching, Chang, Tien-Jyun, Chang, Yi-Cheng, Charpentier, Guillaume, Chen, Chien-Hsiun, Chen, Han, Chen, Yuan-Tsong, Chia, Kee-Seng, Chidambaram, Manickam, Chines, Peter S, Cho, Nam H, Cho, Young Min, Chuang, Lee-Ming, Collins, Francis S, Cornelis, Marylin C, Couper, David J, Crenshaw, Andrew T, van Dam, Rob M, Danesh, John, Das, Debashish, de Faire, Ulf, Dedoussis, George, Deloukas, Panos, Dimas, Antigone S, Dina, Christian, Doney, Alex S, Donnelly, Peter J, Dorkhan, Mozhgan, van Duijn, Cornelia, Dupuis, Josée, Edkins, Sarah, Elliott, Paul, Emilsson, Valur, Erbel, Raimund, Eriksson, Johan G, Escobedo, Jorge, Esko, Tonu, Eury, Elodie, Florez, Jose C, Fontanillas, Pierre, Forouhi, Nita G, Forsen, Tom, Fox, Caroline, Fraser, Ross M, Frayling, Timothy M, Froguel, Philippe, Frossard, Philippe, Gao, Yutang, Gertow, Karl, Gieger, Christian, Gigante, Bruna, Grallert, Harald, Grant, George B, Grrop, Leif C, and Groves, Chrisropher J

Subjects
DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, South Asian Type 2 Diabetes (SAT2D) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Risk Factors, Case-Control Studies, Polymorphism, Single Nucleotide, Alleles, Asian Continental Ancestry Group, European Continental Ancestry Group, Hispanic Americans, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.

Published
2014

16. The genetic architecture of type 2 diabetes

Author

Fuchsberger, Christian, Flannick, Jason, Teslovich, Tanya M., Mahajan, Anubha, Agarwala, Vineeta, Gaulton, Kyle J., Ma, Clement, Fontanillas, Pierre, Moutsianas, Loukas, McCarthy, Davis J., Rivas, Manuel A., Perry, John R. B., Sim, Xueling, Blackwell, Thomas W., Robertson, Neil R., Rayner, N. William, Cingolani, Pablo, Locke, Adam E., Tajes, Juan Fernandez, Highland, Heather M., Dupuis, Josee, Chines, Peter S., Lindgren, Cecilia M., Hartl, Christopher, Jackson, Anne U., Chen, Han, Huyghe, Jeroen R., van de Bunt, Martijn, Pearson, Richard D., Kumar, Ashish, Müller-Nurasyid, Martina, Grarup, Niels, Stringham, Heather M., Gamazon, Eric R., Lee, Jaehoon, Chen, Yuhui, Scott, Robert A., Below, Jennifer E., Chen, Peng, Huang, Jinyan, Go, Min Jin, Stitzel, Michael L., Pasko, Dorota, Parker, Stephen C. J., Varga, Tibor V., Green, Todd, Beer, Nicola L., Day-Williams, Aaron G., Ferreira, Teresa, Fingerlin, Tasha, Horikoshi, Momoko, Hu, Cheng, Huh, Iksoo, Ikram, Mohammad Kamran, Kim, Bong-Jo, Kim, Yongkang, Kim, Young Jin, Kwon, Min-Seok, Lee, Juyoung, Lee, Selyeong, Lin, Keng-Han, Maxwell, Taylor J., Nagai, Yoshihiko, Wang, Xu, Welch, Ryan P., Yoon, Joon, Zhang, Weihua, Barzilai, Nir, Voight, Benjamin F., Han, Bok-Ghee, Jenkinson, Christopher P., Kuulasmaa, Teemu, Kuusisto, Johanna, Manning, Alisa, Ng, Maggie C. Y., Palmer, Nicholette D., Balkau, Beverley, Stančáková, Alena, Abboud, Hanna E., Boeing, Heiner, Giedraitis, Vilmantas, Prabhakaran, Dorairaj, Gottesman, Omri, Scott, James, Carey, Jason, Kwan, Phoenix, Grant, George, Smith, Joshua D., Neale, Benjamin M., Purcell, Shaun, Butterworth, Adam S., Howson, Joanna M. M., Lee, Heung Man, Lu, Yingchang, Kwak, Soo-Heon, Zhao, Wei, Danesh, John, Lam, Vincent K. L., Park, Kyong Soo, Saleheen, Danish, So, Wing Yee, Tam, Claudia H. T., Afzal, Uzma, Aguilar, David, Arya, Rector, Aung, Tin, Chan, Edmund, Navarro, Carmen, Cheng, Ching-Yu, Palli, Domenico, Correa, Adolfo, Curran, Joanne E., Rybin, Denis, Farook, Vidya S., Fowler, Sharon P., Freedman, Barry I., Griswold, Michael, Hale, Daniel Esten, Hicks, Pamela J., Khor, Chiea-Chuen, Kumar, Satish, Lehne, Benjamin, Thuillier, Dorothée, Lim, Wei Yen, Liu, Jianjun, van der Schouw, Yvonne T., Loh, Marie, Musani, Solomon K., Puppala, Sobha, Scott, William R., Yengo, Loïc, Tan, Sian-Tsung, Taylor Jr., Herman A., Thameem, Farook, Wilson, Gregory, Wong, Tien Yin, Njølstad, Pål Rasmus, Levy, Jonathan C., Mangino, Massimo, Bonnycastle, Lori L., Schwarzmayr, Thomas, Fadista, João, Surdulescu, Gabriela L., Herder, Christian, Groves, Christopher J., Wieland, Thomas, Bork-Jensen, Jette, Brandslund, Ivan, Christensen, Cramer, Koistinen, Heikki A., Doney, Alex S. F., Kinnunen, Leena, Esko, Tõnu, Farmer, Andrew J., Hakaste, Liisa, Hodgkiss, Dylan, Kravic, Jasmina, Lyssenko, Valeriya, Hollensted, Mette, Jørgensen, Marit E., Jørgensen, Torben, Ladenvall, Claes, Justesen, Johanne Marie, Käräjämäki, Annemari, Kriebel, Jennifer, Rathmann, Wolfgang, Lannfelt, Lars, Lauritzen, Torsten, Narisu, Narisu, Linneberg, Allan, Melander, Olle, Milani, Lili, Neville, Matt, Orho-Melander, Marju, Qi, Lu, Qi, Qibin, Roden, Michael, Rolandsson, Olov, Swift, Amy, Rosengren, Anders H., Stirrups, Kathleen, Wood, Andrew R., Mihailov, Evelin, Blancher, Christine, Carneiro, Mauricio O., Maguire, Jared, Poplin, Ryan, Shakir, Khalid, Fennell, Timothy, DePristo, Mark, Hrabé de Angelis, Martin, Deloukas, Panos, Gjesing, Anette P., Jun, Goo, Nilsson, Peter, Murphy, Jacquelyn, Onofrio, Robert, Thorand, Barbara, Hansen, Torben, Meisinger, Christa, Hu, Frank B., Isomaa, Bo, Karpe, Fredrik, Liang, Liming, Peters, Annette, Huth, Cornelia, O’Rahilly, Stephen P., Palmer, Colin N. A., Pedersen, Oluf, Rauramaa, Rainer, Tuomilehto, Jaakko, Salomaa, Veikko, Watanabe, Richard M., Syvänen, Ann-Christine, Bergman, Richard N., Bharadwaj, Dwaipayan, Bottinger, Erwin P., Cho, Yoon Shin, Chandak, Giriraj R., Chan, Juliana C. N., Chia, Kee Seng, Daly, Mark J., Ebrahim, Shah B., Langenberg, Claudia, Elliott, Paul, Jablonski, Kathleen A., Lehman, Donna M., Jia, Weiping, Ma, Ronald C. W., Pollin, Toni I., Sandhu, Manjinder, Tandon, Nikhil, Froguel, Philippe, Barroso, Inês, Teo, Yik Ying, Zeggini, Eleftheria, Loos, Ruth J. F., Small, Kerrin S., Ried, Janina S., DeFronzo, Ralph A., Grallert, Harald, Glaser, Benjamin, Metspalu, Andres, Wareham, Nicholas J., Walker, Mark, Banks, Eric, Gieger, Christian, Ingelsson, Erik, Im, Hae Kyung, Illig, Thomas, Franks, Paul W., Buck, Gemma, Trakalo, Joseph, Buck, David, Prokopenko, Inga, Mägi, Reedik, Lind, Lars, Farjoun, Yossi, Owen, Katharine R., Gloyn, Anna L., Strauch, Konstantin, Tuomi, Tiinamaija, Kooner, Jaspal Singh, Lee, Jong-Young, Park, Taesung, Donnelly, Peter, Morris, Andrew D., Hattersley, Andrew T., Bowden, Donald W., Collins, Francis S., Atzmon, Gil, Chambers, John C., Spector, Timothy D., Laakso, Markku, Strom, Tim M., Bell, Graeme I., Blangero, John, Duggirala, Ravindranath, Tai, E. Shyong, McVean, Gilean, Hanis, Craig L., Wilson, James G., Seielstad, Mark, Frayling, Timothy M., Meigs, James B., Cox, Nancy J., Sladek, Rob, Lander, Eric S., Gabriel, Stacey, Burtt, Noël P., Mohlke, Karen L., Meitinger, Thomas, Groop, Leif, Abecasis, Goncalo, Florez, Jose C., Scott, Laura J., Morris, Andrew P., Kang, Hyun Min, Boehnke, Michael, Altshuler, David, and McCarthy, Mark I.

Published
2016
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17. List of Contributors

Author

Abusag, Milad, primary, Arboleda, Valerie, additional, Arnold, Andrew, additional, Assié, Guillaume, additional, Beckers, Albert, additional, Bell, Graeme I., additional, Bertagna, Xavier, additional, Bertherat, Jérôme, additional, Brierley, Gemma V., additional, Cantara, Silvia, additional, Carmody, David, additional, Christensen, Jane Hvarregaard, additional, Clément, Karine, additional, Cummings, Shelly, additional, Daly, Adrian F., additional, Deladoëy, Johnny, additional, Dreijerink, Koen M., additional, Dubern, Béatrice, additional, Dumitrescu, Alexandra M., additional, Ehrmann, David A., additional, Evans, Douglas B., additional, Favus, Murray J., additional, Garg, Abhimanyu, additional, Geurts, Jennifer L., additional, Grasberger, Helmut, additional, Greeley, Siri Atma W., additional, Groussin, Lionel, additional, Höppener, Jo W., additional, Hoffman, Leslie, additional, Holick, Michael F., additional, Huang, Elbert S., additional, Huvenne, Hélène, additional, Hwa, Vivian, additional, Jones, Andrea L., additional, Joseph, Loren J., additional, Kahaly, George J., additional, Koren, Dorit, additional, Lauter, Kelly, additional, Libé, Rossella, additional, Links, Thera P., additional, Lips, Cornelis J., additional, McPhaul, Michael J., additional, Naylor, Rochelle N., additional, New, Maria I., additional, Nielsen, Sarah M., additional, Nimkarn, Saroj, additional, O'Rahilly, Stephen, additional, Pacini, Furio, additional, Palladino, Andrew, additional, Philipson, Louis H., additional, Pohlenz, Joachim, additional, Radovick, Sally, additional, Raygada, Margarita, additional, Refetoff, Samuel, additional, Rich, Thereasa A., additional, Rinkes, Inne Borel, additional, Rittig, Søren, additional, Romero, Christopher J., additional, Rosenfeld, Ron G., additional, Rostomyan, Liliya, additional, Savage, David B., additional, Semple, Robert K., additional, Støy, Julie, additional, Stratakis, Constantine A., additional, Strauss, Bernard S., additional, Timmers, Marc, additional, Tounian, Patrick, additional, Valk, Gerlof D., additional, van der Horst-Schrivers, Anouk N.A., additional, van der Luijt, Rob B., additional, van Nesselrooij, Bernadette P.M., additional, Van Vliet, Guy, additional, Vilain, Eric, additional, Vriens, Menno, additional, Wang, Tracy S., additional, Weiss, Roy E., additional, Yau, Mabel, additional, and Zuchner, Stephan, additional

Published
2016
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18. Contributors

Author

Aiello, Lloyd Paul, primary, Alatzoglou, Kyriaki S., additional, Alexander, Erik K., additional, Allan, Carolyn A., additional, Allolio, Bruno, additional, Amino, Nobuyuki, additional, Anawalt, Bradley D., additional, Angelos, Peter, additional, Arboleda, Valerie A., additional, Auchus, Richard J., additional, Axelrod, Lloyd, additional, Bahn, Rebecca S., additional, Baker, MD, PhD, FRACP, H.W. Gordon, additional, Barak, Shlomi, additional, Barnes, Randall B., additional, Barthel, Andreas, additional, Bastepe, Murat, additional, Beardsley, Emma K., additional, Beck-Peccoz, Paolo, additional, Bell, Graeme I., additional, Bi, Wenya Linda, additional, Bilezikian, John P., additional, Blum, Manfred, additional, Bonnema, Steen J., additional, Bornstein, Stefan R., additional, Bouillon, Roger, additional, Boulton, Andrew J.M., additional, Braunstein, Glenn D., additional, Bringhurst, F. Richard, additional, Broekmans, Frank J., additional, Bronstein, Marcello D., additional, Brown, Edward M., additional, Brown, Wendy A., additional, Bulun, Serdar E., additional, Burch, Henry B., additional, Burger, Henry G., additional, Burney, Richard O., additional, Burt, Morton G., additional, Cagliero, Enrico, additional, Callender, Glenda G., additional, Avancini Caramori, Maria Luiza, additional, Carey, Robert M., additional, Carling, Tobias, additional, Cavagnini, Francesco, additional, Cavallerano, Jerry D., additional, Challet, Etienne, additional, Chan, Shu Jin, additional, Chang, R. Jeffrey, additional, Chapurlat, Roland D., additional, Chatterjee, V. Krishna, additional, Chiofalo, Francesco, additional, Chiovato, Luca, additional, Cho, Kyung J., additional, Christison-Lagay, Emily, additional, Christophe, Daniel, additional, Chrousos, George P., additional, Cidlowski, John A., additional, Clemmons, David R., additional, Considine, Robert V., additional, Conti, Marco, additional, Copinschi, Georges, additional, Copps, Kyle D., additional, Cowley, Michael A., additional, Cuttler, Leona, additional, Dattani, Mehul T., additional, Davis, Stephen N., additional, De Felice, Mario, additional, De Groot, Leslie J., additional, de Kretser, David M., additional, DeFronzo, Ralph A., additional, Delli, Ahmed J., additional, Demay, Marie B., additional, Dennedy, Michael C., additional, Di Lauro, Roberto, additional, Dineen, Rosemary, additional, Ding, Su Ann, additional, Dinneen, Sean F., additional, Drucker, Daniel J., additional, Dumont, Jacques E., additional, Dungan, Kathleen M., additional, Dunn, Ian F., additional, Econs, Michael J., additional, Ehrmann, David A., additional, Eisenhofer, Graeme, additional, Ergun-Longmire, Berrin, additional, Eugster, Erica A., additional, Farooqi, Sadaf I., additional, Fassnacht, Martin, additional, Fauser, Bart C.J.M., additional, Fenzi, Gianfranco, additional, Ferrannini, Ele, additional, Findlay, David M., additional, Finlayson, Courtney Anne, additional, Fisher, Delbert A., additional, Francis, Isaac R., additional, Freeman, Mason W., additional, Frohman, Lawrence A., additional, Frydenberg, Mark, additional, Fuller, Peter J., additional, Gaglia, Jason L., additional, Galizia, Gianluigi, additional, Gardella, Thomas J., additional, Garvey, Katharine C., additional, Genant, Harry K., additional, German, Michael S., additional, Gevers, Evelien F., additional, Giraldi, Francesca Pecori, additional, Giudice, Linda C., additional, Giustina, Andrea, additional, Glasier, Anna, additional, Glorieux, Francis H., additional, Goldfine, Allison B., additional, Gooren, Louis J., additional, Gordon, David F., additional, Gregerson, Karen A., additional, Grogan, Raymon H., additional, Gross, Milton D., additional, Grossman, Ashley B., additional, Gruber, Matthias, additional, Guimarães, Valeria C., additional, Gurnell, Mark, additional, Haddad, Nadine G., additional, Haisenleder, Daniel J., additional, Handelsman, David J., additional, Hanks, John B., additional, Hannon, Mark J., additional, Harno, Erika, additional, Hebrok, Matthias, additional, Hedger, Mark P., additional, Hegedüs, Laszlo, additional, Heindel, Jerrold J., additional, Hernandez, Arturo, additional, Herndon, Maria K., additional, Ho, Ken K.Y., additional, Horseman, Nelson D., additional, Hughes, Ieuan A., additional, Hupfeld, Christopher J., additional, Hussain, Hero K., additional, Iodice, Valeria, additional, James, Benjamin C., additional, Jameson, J. Larry, additional, Jones, Glenville, additional, Josso, Nathalie, additional, Jüppner, Harald, additional, Juszczak, Agata, additional, Kalish, Jeffrey, additional, Kaplan, Edwin L., additional, Karavitaki, Niki, additional, Karczewska-Kupczewska, Monika, additional, Khattab, Ahmed, additional, Klein, David C., additional, Klein, Ronald, additional, Kleinau, Gunnar, additional, Koontz, Michaela, additional, Kopchick, John J., additional, Kopp, Peter, additional, Kowalska, Irina, additional, Krane, Stephen M., additional, Krohn, Knut, additional, Kronenberg, Henry M., additional, Lamos, Elizabeth M., additional, Lania, Andrea, additional, Lau, Sue Lynn, additional, Laws, Edward R., additional, Lazarus, John H., additional, Learoyd, Diana L., additional, Lebovitz, Harold E., additional, Lenmark, Åke, additional, List, Edward O., additional, Loveland, Kate, additional, Low, David A., additional, Macchia, Paolo E., additional, Maclaren, Noel K., additional, Madeiros-Neto, Geraldo, additional, Maenhaut, Carine, additional, Maes, Christa, additional, Main, Katharina M., additional, Malchoff, Carl D., additional, Malchoff, Diana M., additional, Malik, Rayaz A., additional, Mandel, Susan J., additional, Mantzoros, Christos S., additional, Maratos-Flier, Eleftheria, additional, Marino, Michele, additional, Marshall, John C., additional, Martin, T. John, additional, Martin, Thomas F.J., additional, Mathias, Christopher J., additional, McGee, Elizabeth A., additional, McKenzie, Travis, additional, McLachlan, Robert I., additional, Meier, Juris J., additional, Melmed, Shlomo, additional, Metzger, Boyd E., additional, Meyer-Bahlburg, Heino F.L., additional, Millar, Robert P., additional, Miller, Walter L., additional, Misra, Madhusmita, additional, Molitch, Mark E., additional, Moravek, Molly B., additional, Morris, Damian G., additional, Nagar, Sapna, additional, Nakamoto, Jon, additional, New, Maria I., additional, Nieman, Lynnette K., additional, Nilson, John H., additional, Ntali, Georgia, additional, O’Bryan, Moira, additional, O’Rahilly, Stephen, additional, Öberg, Kjell, additional, Olefsky, Jerrold M., additional, Olson, Matthew T., additional, Pacak, Karel, additional, Pacini, Furio, additional, Padia, Shetal H., additional, Paschke, Ralf, additional, Pasquel, Francisco J., additional, Perry, Katherine Wesseling, additional, Persani, Luca, additional, Philipson, Louis H., additional, Pina, Christian, additional, Pomposelli, Frank B., additional, Potts, John T., additional, Quigley, Charmian A., additional, Quinkler, Marcus O., additional, Quirk, Christine Campion, additional, Rajpert-De Meyts, Ewa, additional, Ravussin, Eric, additional, Ray, David W., additional, Refetoff, Samuel, additional, Retnakaran, Ravi, additional, Rey, Rodolfo A., additional, Rhodes, Christopher J., additional, Ridgway, E. Chester, additional, Risbridger, Gail P., additional, Rizza, Robert A., additional, Robinson, Bruce G., additional, Roger, Pierre P., additional, Rosenfeld, Michael G., additional, Rosenfield, Robert L., additional, Rossing, Peter, additional, Rubin, Robert T., additional, Rubio, Ileana G.S., additional, Ruderman, Neil B., additional, Russo, Jose, additional, Russo, Irma H., additional, Salusky, Isidro B., additional, Santoro, Nanette, additional, Scully, Kathleen M., additional, Sexton, Patrick M., additional, Shulman, Gerald I., additional, Silva, Paolo S., additional, Silverberg, Shonni J., additional, Singer, Frederick R., additional, Skakkebaek, Niels E., additional, Skaznik-Wikiel, Malgorzata E., additional, Skowronska-Krawczyk, Dorota, additional, Smith, Carolyn L., additional, Smith, Philip W., additional, Smith, Roger, additional, Smith, Steven R., additional, Snyder, Peter J., additional, St. Germain, Donald L., additional, St-Arnaud, René, additional, Steiner, Donald F., additional, Stewart, Paul M., additional, Strączkowski, Marek, additional, Strauss, Jerome F., additional, Styne, Dennis M., additional, Swan, Karena L., additional, Swerdloff, Ronald S., additional, Tacon, Lyndal J., additional, Tello, Javier A., additional, Thakker, Rajesh V., additional, Thompson, Christopher J., additional, Timmers, Henri J.L.M., additional, Toppari, Jorma, additional, Traub, Michael L., additional, Tsoukas, Michael A., additional, Udelsman, Robert, additional, Umpierrez, Guillermo E., additional, Van den Berghe, Greet, additional, Vassart, Gilbert, additional, Vernon, Ashley H., additional, Vilain, Eric, additional, Visser, Theo J., additional, Vitti, Paolo, additional, Walford, Geoffrey A., additional, Wang, Christina, additional, Weetman, Anthony P., additional, Weigel, Nancy L., additional, Weir, Gordon C., additional, Weiss, Roy E., additional, White, Anne, additional, White, Kenneth E., additional, White, Morris F., additional, Whyte, Michael P., additional, Wiersinga, Wilmar M., additional, Willenberg, Holger S., additional, Wolfsdorf, Joseph I., additional, Wondisford, Fredric E., additional, Wong, Ka Kit, additional, Wysolmerski, John J., additional, Yau, Mabel, additional, Young, Morag J., additional, Younk, Lisa M., additional, Yu, Run, additional, Yuen, Tony, additional, Zeiger, Martha A., additional, Zinman, Bernard, additional, and Zoeller, R. Thomas, additional

Published
2016
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21. Insulin Gene Mutations as a Cause of Permanent Neonatal Diabetes

Author

Støy, Julie, Edghill, Emma L., Flanagan, Sarah E., Ye, Honggang, Paz, Veronica P., Pluzhnikov, Anna, Below, Jennifer E., Hayes, M. Geoffrey, Cox, Nancy J., Lipkind, Gregory M., Lipton, Rebecca B., Greeley, Siri Atma W., Patch, Ann-Marie, Ellard, Sian, Steiner, Donald F., Hattersley, Andrew T., Philipson, Louis H., and Bell, Graeme I.

Published
2007
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26. Insight on Diagnosis and Treatment From Over a Decade of Research Through the University of Chicago Monogenic Diabetes Registry

Author

Bowden, Tiana L., primary, Letourneau-Freiberg, Lisa R., additional, Kandasamy, Balamurugan, additional, Sanyoura, May, additional, Tian, Persephone, additional, Harris, Anastasia G., additional, Bell, Graeme I., additional, Philipson, Louis H., additional, Naylor, Rochelle N., additional, and Greeley, Siri Atma W., additional

Published
2021
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