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1. Genome‐Wide Study of Subcutaneous and Visceral Adipose Tissue Reveals Novel Sex‐Specific Adiposity Loci in Mexican Americans

Author

Gao, Chuan, Langefeld, Carl D, Ziegler, Julie T, Taylor, Kent D, Norris, Jill M, Chen, Yii‐Der I, Hellwege, Jacklyn N, Guo, Xiuqing, Allison, Matthew A, Speliotes, Elizabeth K, Rotter, Jerome I, Bowden, Donald W, Wagenknecht, Lynne E, and Palmer, Nicholette D

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Obesity, Nutrition, Prevention, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Adipose Tissue, Adiposity, Body Mass Index, Female, Genome-Wide Association Study, Genotype, Humans, Male, Mexican Americans, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk Factors, Endocrinology & Metabolism
Abstract

ObjectiveThis study aimed to explore the genetic mechanisms of regional fat deposition, which is a strong risk factor for metabolic diseases beyond total adiposity.MethodsA genome-wide association study of 7,757,139 single-nucleotide polymorphisms (SNPs) in 983 Mexican Americans (nmale  = 403; nfemale  = 580) from the Insulin Resistance Atherosclerosis Family Study was performed. Association analyses were performed with and without sex stratification for subcutaneous adipose tissue, visceral adipose tissue (VAT), and visceral-subcutaneous ratio (VSR) obtained from computed tomography.ResultsThe strongest signal identified was SNP rs2185405 (minor allele frequencies [MAF] = 40%; PVAT  = 1.98 × 10-8 ) with VAT. It is an intronic variant of the GLIS family zinc finger 3 gene (GLIS3). In addition, SNP rs12657394 (MAF = 19%) was associated with VAT in males (Pmale  = 2.39×10-8 ; Pfemale  = 2.5 × 10-3 ). It is located intronically in the serum response factor binding protein 1 gene (SRFBP1). On average, male carriers of the variant had 24.6 cm2 increased VAT compared with noncarriers. Subsequently, genome-wide SNP-sex interaction analysis was performed. SNP rs10913233 (MAF = 14%; Pint  = 3.07 × 10-8 ) in PAPPA2 and rs10923724 (MAF = 38%; Pint  = 2.89 × 10-8 ) upstream of TBX15 were strongly associated with the interaction effect for VSR.ConclusionsSix loci were identified with genome-wide significant associations with fat deposition and interactive effects. These results provided genetic evidence for a differential basis of fat deposition between genders.

Published
2018

3. Trans-ethnic Meta-analysis and Functional Annotation Illuminates the Genetic Architecture of Fasting Glucose and Insulin

Author

Liu, Ching-Ti, Raghavan, Sridharan, Maruthur, Nisa, Kabagambe, Edmond Kato, Hong, Jaeyoung, Ng, Maggie CY, Hivert, Marie-France, Lu, Yingchang, An, Ping, Bentley, Amy R, Drolet, Anne M, Gaulton, Kyle J, Guo, Xiuqing, Armstrong, Loren L, Irvin, Marguerite R, Li, Man, Lipovich, Leonard, Rybin, Denis V, Taylor, Kent D, Agyemang, Charles, Palmer, Nicholette D, Cade, Brian E, Chen, Wei-Min, Dauriz, Marco, Delaney, Joseph AC, Edwards, Todd L, Evans, Daniel S, Evans, Michele K, Lange, Leslie A, Leong, Aaron, Liu, Jingmin, Liu, Yongmei, Nayak, Uma, Patel, Sanjay R, Porneala, Bianca C, Rasmussen-Torvik, Laura J, Snijder, Marieke B, Stallings, Sarah C, Tanaka, Toshiko, Yanek, Lisa R, Zhao, Wei, Becker, Diane M, Bielak, Lawrence F, Biggs, Mary L, Bottinger, Erwin P, Bowden, Donald W, Chen, Guanjie, Correa, Adolfo, Couper, David J, Crawford, Dana C, Cushman, Mary, Eicher, John D, Fornage, Myriam, Franceschini, Nora, Fu, Yi-Ping, Goodarzi, Mark O, Gottesman, Omri, Hara, Kazuo, Harris, Tamara B, Jensen, Richard A, Johnson, Andrew D, Jhun, Min A, Karter, Andrew J, Keller, Margaux F, Kho, Abel N, Kizer, Jorge R, Krauss, Ronald M, Langefeld, Carl D, Li, Xiaohui, Liang, Jingling, Liu, Simin, Lowe, William L, Mosley, Thomas H, North, Kari E, Pacheco, Jennifer A, Peyser, Patricia A, Patrick, Alan L, Rice, Kenneth M, Selvin, Elizabeth, Sims, Mario, Smith, Jennifer A, Tajuddin, Salman M, Vaidya, Dhananjay, Wren, Mary P, Yao, Jie, Zhu, Xiaofeng, Ziegler, Julie T, Zmuda, Joseph M, Zonderman, Alan B, Zwinderman, Aeilko H, Consortium, AAAG, Consortium, CARe, Consortium, COGENT-BP, Consortium, eMERGE, Consortium, MEDIA, Adeyemo, Adebowale, Boerwinkle, Eric, Ferrucci, Luigi, Hayes, M Geoffrey, and Kardia, Sharon LR

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Health Disparities, Human Genome, Diabetes, Minority Health, Metabolic and endocrine, Asian People, Black People, Blood Glucose, Diabetes Mellitus, Type 2, Enhancer Elements, Genetic, Ethnicity, Fasting, Female, Gene Frequency, Genome-Wide Association Study, Humans, Insulin, Insulin Resistance, Introns, Islets of Langerhans, Male, Molecular Sequence Annotation, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Racial Groups, Transcription Factors, White People, AAAG Consortium, CARe Consortium, COGENT-BP Consortium, eMERGE Consortium, MEDIA Consortium, MAGIC Consortium, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Knowledge of the genetic basis of the type 2 diabetes (T2D)-related quantitative traits fasting glucose (FG) and insulin (FI) in African ancestry (AA) individuals has been limited. In non-diabetic subjects of AA (n = 20,209) and European ancestry (EA; n = 57,292), we performed trans-ethnic (AA+EA) fine-mapping of 54 established EA FG or FI loci with detailed functional annotation, assessed their relevance in AA individuals, and sought previously undescribed loci through trans-ethnic (AA+EA) meta-analysis. We narrowed credible sets of variants driving association signals for 22/54 EA-associated loci; 18/22 credible sets overlapped with active islet-specific enhancers or transcription factor (TF) binding sites, and 21/22 contained at least one TF motif. Of the 54 EA-associated loci, 23 were shared between EA and AA. Replication with an additional 10,096 AA individuals identified two previously undescribed FI loci, chrX FAM133A (rs213676) and chr5 PELO (rs6450057). Trans-ethnic analyses with regulatory annotation illuminate the genetic architecture of glycemic traits and suggest gene regulation as a target to advance precision medicine for T2D. Our approach to utilize state-of-the-art functional annotation and implement trans-ethnic association analysis for discovery and fine-mapping offers a framework for further follow-up and characterization of GWAS signals of complex trait loci.

Published
2016

4. Lupus Risk Variant Increases pSTAT1 Binding and Decreases ETS1 Expression

Author

Lu, Xiaoming, Zoller, Erin E, Weirauch, Matthew T, Wu, Zhiguo, Namjou, Bahram, Williams, Adrienne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, Glenn, Stuart B, Adler, Adam, Shen, Nan, Nath, Swapan K, Stevens, Anne M, Freedman, Barry I, Tsao, Betty P, Jacob, Chaim O, Kamen, Diane L, Brown, Elizabeth E, Gilkeson, Gary S, Alarcón, Graciela S, Reveille, John D, Anaya, Juan-Manuel, James, Judith A, Sivils, Kathy L, Criswell, Lindsey A, Vilá, Luis M, Alarcón-Riquelme, Marta E, Petri, Michelle, Scofield, R Hal, Kimberly, Robert P, Ramsey-Goldman, Rosalind, Bin Joo, Young, Choi, Jeongim, Bae, Sang-Cheol, Boackle, Susan A, Graham, Deborah Cunninghame, Vyse, Timothy J, Guthridge, Joel M, Gaffney, Patrick M, Langefeld, Carl D, Kelly, Jennifer A, Greis, Kenneth D, Kaufman, Kenneth M, Harley, John B, and Kottyan, Leah C

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Biotechnology, Lupus, Autoimmune Disease, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Alleles, Animals, Asian People, Bayes Theorem, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Lupus Erythematosus, Systemic, Mice, Protein Binding, Proto-Oncogene Protein c-ets-1, STAT1 Transcription Factor, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genetic variants at chromosomal region 11q23.3, near the gene ETS1, have been associated with systemic lupus erythematosus (SLE), or lupus, in independent cohorts of Asian ancestry. Several recent studies have implicated ETS1 as a critical driver of immune cell function and differentiation, and mice deficient in ETS1 develop an SLE-like autoimmunity. We performed a fine-mapping study of 14,551 subjects from multi-ancestral cohorts by starting with genotyped variants and imputing to all common variants spanning ETS1. By constructing genetic models via frequentist and Bayesian association methods, we identified 16 variants that are statistically likely to be causal. We functionally assessed each of these variants on the basis of their likelihood of affecting transcription factor binding, miRNA binding, or chromatin state. Of the four variants that we experimentally examined, only rs6590330 differentially binds lysate from B cells. Using mass spectrometry, we found more binding of the transcription factor signal transducer and activator of transcription 1 (STAT1) to DNA near the risk allele of rs6590330 than near the non-risk allele. Immunoblot analysis and chromatin immunoprecipitation of pSTAT1 in B cells heterozygous for rs6590330 confirmed that the risk allele increased binding to the active form of STAT1. Analysis with expression quantitative trait loci indicated that the risk allele of rs6590330 is associated with decreased ETS1 expression in Han Chinese, but not other ancestral cohorts. We propose a model in which the risk allele of rs6590330 is associated with decreased ETS1 expression and increases SLE risk by enhancing the binding of pSTAT1.

Published
2015

5. Genetic Variants Associated With Quantitative Glucose Homeostasis Traits Translate to Type 2 Diabetes in Mexican Americans: The GUARDIAN (Genetics Underlying Diabetes in Hispanics) Consortium

Author

Palmer, Nicholette D, Goodarzi, Mark O, Langefeld, Carl D, Wang, Nan, Guo, Xiuqing, Taylor, Kent D, Fingerlin, Tasha E, Norris, Jill M, Buchanan, Thomas A, Xiang, Anny H, Haritunians, Talin, Ziegler, Julie T, Williams, Adrienne H, Stefanovski, Darko, Cui, Jinrui, Mackay, Adrienne W, Henkin, Leora F, Bergman, Richard N, Gao, Xiaoyi, Gauderman, James, Varma, Rohit, Hanis, Craig L, Cox, Nancy J, Highland, Heather M, Below, Jennifer E, Williams, Amy L, Burtt, Noel P, Aguilar-Salinas, Carlos A, Huerta-Chagoya, Alicia, Gonzalez-Villalpando, Clicerio, Orozco, Lorena, Haiman, Christopher A, Tsai, Michael Y, Johnson, W Craig, Yao, Jie, Rasmussen-Torvik, Laura, Pankow, James, Snively, Beverly, Jackson, Rebecca D, Liu, Simin, Nadler, Jerry L, Kandeel, Fouad, Chen, Yii-Der I, Bowden, Donald W, Rich, Stephen S, Raffel, Leslie J, Rotter, Jerome I, Watanabe, Richard M, and Wagenknecht, Lynne E

Subjects
Biomedical and Clinical Sciences, Obesity, Clinical Research, Diabetes, Human Genome, Genetics, Metabolic and endocrine, Blood Glucose, Databases, Factual, Diabetes Mellitus, Type 2, Gene Expression Regulation, Genetic Variation, Genome, Genome-Wide Association Study, Genotype, Hispanic or Latino, Homeostasis, Humans, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Insulin sensitivity, insulin secretion, insulin clearance, and glucose effectiveness exhibit strong genetic components, although few studies have examined their genetic architecture or influence on type 2 diabetes (T2D) risk. We hypothesized that loci affecting variation in these quantitative traits influence T2D. We completed a multicohort genome-wide association study to search for loci influencing T2D-related quantitative traits in 4,176 Mexican Americans. Quantitative traits were measured by the frequently sampled intravenous glucose tolerance test (four cohorts) or euglycemic clamp (three cohorts), and random-effects models were used to test the association between loci and quantitative traits, adjusting for age, sex, and admixture proportions (Discovery). Analysis revealed a significant (P < 5.00 × 10(-8)) association at 11q14.3 (MTNR1B) with acute insulin response. Loci with P < 0.0001 among the quantitative traits were examined for translation to T2D risk in 6,463 T2D case and 9,232 control subjects of Mexican ancestry (Translation). Nonparametric meta-analysis of the Discovery and Translation cohorts identified significant associations at 6p24 (SLC35B3/TFAP2A) with glucose effectiveness/T2D, 11p15 (KCNQ1) with disposition index/T2D, and 6p22 (CDKAL1) and 11q14 (MTNR1B) with acute insulin response/T2D. These results suggest that T2D and insulin secretion and sensitivity have both shared and distinct genetic factors, potentially delineating genomic components of these quantitative traits that drive the risk for T2D.

Published
2015

6. Empirical characteristics of family-based linkage to a complex trait: the ADIPOQ region and adiponectin levels

Author

Hellwege, Jacklyn N, Palmer, Nicholette D, Brown, Mark W, Ziegler, Julie T, An, Sandy S, Guo, Xiuqing, Chen, Ida Y-D, Taylor, Kent, Hawkins, Gregory A, Ng, Maggie CY, Speliotes, Elizabeth K, Lorenzo, Carlos, Norris, Jill M, Rotter, Jerome I, Wagenknecht, Lynne E, Langefeld, Carl D, and Bowden, Donald W

Subjects
Biological Sciences, Genetics, Human Genome, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Adiponectin, Adolescent, Adult, Aged, Aged, 80 and over, Databases, Nucleic Acid, Datasets as Topic, Family, Female, Genetic Linkage, Genetic Loci, Hispanic or Latino, Humans, Lod Score, Male, Microsatellite Repeats, Middle Aged, Polymorphism, Single Nucleotide, Complementary and Alternative Medicine, Paediatrics and Reproductive Medicine, Genetics & Heredity, Reproductive medicine
Abstract

We previously identified a low-frequency (1.1 %) coding variant (G45R; rs200573126) in the adiponectin gene (ADIPOQ) which was the basis for a multipoint microsatellite linkage signal (LOD = 8.2) for plasma adiponectin levels in Hispanic families. We have empirically evaluated the ability of data from targeted common variants, exome chip genotyping, and genome-wide association study data to detect linkage and association to adiponectin protein levels at this locus. Simple two-point linkage and association analyses were performed in 88 Hispanic families (1,150 individuals) using 10,958 SNPs on chromosome 3. Approaches were compared for their ability to map the functional variant, G45R, which was strongly linked (two-point LOD = 20.98) and powerfully associated (p value = 8.1 × 10(-50)). Over 450 SNPs within a broad 61 Mb interval around rs200573126 showed nominal evidence of linkage (LOD > 3) but only four other SNPs in this region were associated with p values

Published
2015

7. A Comprehensive Analysis of Common and Rare Variants to Identify Adiposity Loci in Hispanic Americans: The IRAS Family Study (IRASFS)

Author

Gao, Chuan, Wang, Nan, Guo, Xiuqing, Ziegler, Julie T, Taylor, Kent D, Xiang, Anny H, Hai, Yang, Kridel, Steven J, Nadler, Jerry L, Kandeel, Fouad, Raffel, Leslie J, Chen, Yii-Der I, Norris, Jill M, Rotter, Jerome I, Watanabe, Richard M, Wagenknecht, Lynne E, Bowden, Donald W, Speliotes, Elizabeth K, Goodarzi, Mark O, Langefeld, Carl D, and Palmer, Nicholette D

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Clinical Research, Nutrition, Aging, Prevention, Human Genome, Obesity, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Oral and gastrointestinal, Stroke, Metabolic and endocrine, Cancer, Adiposity, Genetic Association Studies, Genetic Predisposition to Disease, Hispanic or Latino, Humans, Isocitrate Dehydrogenase, Membrane Proteins, Polymorphism, Single Nucleotide, General Science & Technology
Abstract

Obesity is growing epidemic affecting 35% of adults in the United States. Previous genome-wide association studies (GWAS) have identified numerous loci associated with obesity. However, the majority of studies have been completed in Caucasians focusing on total body measures of adiposity. Here we report the results from genome-wide and exome chip association studies focusing on total body measures of adiposity including body mass index (BMI), percent body fat (PBF) and measures of fat deposition including waist circumference (WAIST), waist-hip ratio (WHR), subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) in Hispanic Americans (nmax = 1263) from the Insulin Resistance Atherosclerosis Family Study (IRASFS). Five SNPs from two novel loci attained genome-wide significance (P

Published
2015

8. Fine mapping of Xq28: both MECP2 and IRAK1 contribute to risk for systemic lupus erythematosus in multiple ancestral groups

Author

Kaufman, Kenneth M, Zhao, Jian, Kelly, Jennifer A, Hughes, Travis, Adler, Adam, Sanchez, Elena, Ojwang, Joshua O, Langefeld, Carl D, Ziegler, Julie T, Williams, Adrienne H, Comeau, Mary E, Marion, Miranda C, Glenn, Stuart B, Cantor, Rita M, Grossman, Jennifer M, Hahn, Bevra H, Song, Yeong Wook, Yu, Chack-Yung, James, Judith A, Guthridge, Joel M, Brown, Elizabeth E, Alarcón, Graciela S, Kimberly, Robert P, Edberg, Jeffrey C, Ramsey-Goldman, Rosalind, Petri, Michelle A, Reveille, John D, Vilá, Luis M, Anaya, Juan-Manuel, Boackle, Susan A, Stevens, Anne M, Freedman, Barry I, Criswell, Lindsey A, Group, Bernardo A Pons-Estel on behalf of the Argentine Collaborative, Lee, Joo-Hyun, Lee, Ji-Seon, Chang, Deh-Ming, Scofield, R Hal A, Gilkeson, Gary S, Merrill, Joan T, Niewold, Timothy B, Vyse, Timothy James, Bae, Sang-Cheol, network, Marta E Alarcón-Riquelme on behalf of the BIOLUPUS, Jacob, Chaim O, Sivils, Kathy Moser, Gaffney, Patrick M, Harley, John B, Sawalha, Amr H, and Tsao, Betty P

Subjects
Human Genome, Autoimmune Disease, Lupus, Genetics, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Base Sequence, Chromosome Mapping, Chromosomes, Human, X, Genetic Predisposition to Disease, Genotype, Haplotypes, Humans, Interleukin-1 Receptor-Associated Kinases, Lupus Erythematosus, Systemic, Methyl-CpG-Binding Protein 2, Molecular Sequence Data, Polymorphism, Single Nucleotide, Racial Groups, Real-Time Polymerase Chain Reaction, Risk Factors, Argentine Collaborative Group, BIOLUPUS network, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology
Abstract

ObjectivesThe Xq28 region containing IRAK1 and MECP2 has been identified as a risk locus for systemic lupus erythematosus (SLE) in previous genetic association studies. However, due to the strong linkage disequilibrium between IRAK1 and MECP2, it remains unclear which gene is affected by the underlying causal variant(s) conferring risk of SLE.MethodsWe fine-mapped ≥136 SNPs in a ∼227 kb region on Xq28, containing IRAK1, MECP2 and seven adjacent genes (L1CAM, AVPR2, ARHGAP4, NAA10, RENBP, HCFC1 and TMEM187), for association with SLE in 15 783 case-control subjects derived from four different ancestral groups.ResultsMultiple SNPs showed strong association with SLE in European Americans, Asians and Hispanics at p

Published
2013

9. Association of two independent functional risk haplotypes in TNIP1 with systemic lupus erythematosus

Author

Adrianto, Indra, Wang, Shaofeng, Wiley, Graham B, Lessard, Christopher J, Kelly, Jennifer A, Adler, Adam J, Glenn, Stuart B, Williams, Adrienne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, Wakeland, Benjamin E, Liang, Chaoying, Kaufman, Kenneth M, Guthridge, Joel M, Alarcón‐Riquelme, Marta E, Networks, BIOLUPUS and GENLES, Alarcón, Graciela S, Anaya, Juan‐Manuel, Bae, Sang‐Cheol, Kim, Jae‐Hoon, Bin Joo, Young, Boackle, Susan A, Brown, Elizabeth E, Petri, Michelle A, Ramsey‐Goldman, Rosalind, Reveille, John D, Vilá, Luis M, Criswell, Lindsey A, Edberg, Jeffrey C, Freedman, Barry I, Gilkeson, Gary S, Jacob, Chaim O, James, Judith A, Kamen, Diane L, Kimberly, Robert P, Martín, Javier, Merrill, Joan T, Niewold, Timothy B, Pons‐Estel, Bernardo A, Scofield, R Hal, Stevens, Anne M, Tsao, Betty P, Vyse, Timothy J, Langefeld, Carl D, Harley, John B, Wakeland, Edward K, Moser, Kathy L, Montgomery, Courtney G, and Gaffney, Patrick M

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Clinical Research, Human Genome, Lupus, Autoimmune Disease, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, Adaptor Proteins, Signal Transducing, Black or African American, Asian, B-Lymphocytes, Cell Line, Transformed, DNA-Binding Proteins, Female, Genetic Markers, Genetic Predisposition to Disease, Haplotypes, Hispanic or Latino, Humans, Intracellular Signaling Peptides and Proteins, Lupus Erythematosus, Systemic, Male, Neoplasm Proteins, Polymorphism, Single Nucleotide, Risk Factors, United States, White People, BIOLUPUS and GENLES Networks, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and altered type I interferon expression. Genetic surveys and genome-wide association studies have identified >30 SLE susceptibility genes. One of these genes, TNIP1, encodes the ABIN1 protein. ABIN1 functions in the immune system by restricting NF-κB signaling. The present study was undertaken to investigate the genetic factors that influence association with SLE in genes that regulate the NF-κB pathway.MethodsWe analyzed a dense set of genetic markers spanning TNIP1 and TAX1BP1, as well as the TNIP1 homolog TNIP2, in case-control populations of diverse ethnic origins. TNIP1, TNIP2, and TAX1BP1 were fine-mapped in a total of 8,372 SLE cases and 7,492 healthy controls from European-ancestry, African American, Hispanic, East Asian, and African American Gullah populations. Levels of TNIP1 messenger RNA (mRNA) and ABIN1 protein in Epstein-Barr virus-transformed human B cell lines were analyzed by quantitative reverse transcription-polymerase chain reaction and Western blotting, respectively.ResultsWe found significant associations between SLE and genetic variants within TNIP1, but not in TNIP2 or TAX1BP1. After resequencing and imputation, we identified 2 independent risk haplotypes within TNIP1 in individuals of European ancestry that were also present in African American and Hispanic populations. Levels of TNIP1 mRNA and ABIN1 protein were reduced among subjects with these haplotypes, suggesting that they harbor hypomorphic functional variants that influence susceptibility to SLE by restricting ABIN1 expression.ConclusionOur results confirm the association signals between SLE and TNIP1 variants in multiple populations and provide new insight into the mechanism by which TNIP1 variants may contribute to SLE pathogenesis.

Published
2012

10. Impact of genetic ancestry and sociodemographic status on the clinical expression of systemic lupus erythematosus in American Indian–European populations

Author

Sánchez, Elena, Rasmussen, Astrid, Riba, Laura, Acevedo‐Vasquez, Eduardo, Kelly, Jennifer A, Langefeld, Carl D, Williams, Adrianne H, Ziegler, Julie T, Comeau, Mary E, Marion, Miranda C, La Torre, Ignacio García‐De, Maradiaga‐Ceceña, Marco A, Cardiel, Mario H, Esquivel‐Valerio, Jorge A, Rodriguez‐Amado, Jacqueline, Moctezuma, José Francisco, Miranda, Pedro, Perandones, Carlos E, Castel, Cecilia, Laborde, Hugo A, Alba, Paula, Musuruana, Jorge L, Goecke, I Annelise, Anaya, Juan‐Manuel, Kaufman, Kenneth M, Adler, Adam, Glenn, Stuart B, Brown, Elizabeth E, Alarcón, Graciela S, Kimberly, Robert P, Edberg, Jeffrey C, Vilá, Luis M, Criswell, Lindsey A, Gilkeson, Gary S, Niewold, Timothy B, Martín, Javier, Vyse, Timothy J, Boackle, Susan A, Ramsey‐Goldman, Rosalind, Scofield, R Hal, Petri, Michelle, Merrill, Joan T, Reveille, John D, Tsao, Betty P, Orozco, Lorena, Baca, Vicente, Moser, Kathy L, Gaffney, Patrick M, James, Judith A, Harley, John B, Tusié‐Luna, Teresa, Pons‐Estel, Bernardo A, Jacob, Chaim O, and Alarcón‐Riquelme, Marta E

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Health Sciences, Genetics, Autoimmune Disease, Clinical Research, Lupus, Kidney Disease, American Indian or Alaska Native, Inflammatory and immune system, Adolescent, Adult, Child, Female, Genetic Predisposition to Disease, Genotype, Humans, Indians, North American, Indians, South American, Lupus Erythematosus, Systemic, Lupus Nephritis, Male, Middle Aged, Morbidity, Prevalence, Risk Factors, Socioeconomic Factors, White People, Young Adult, Clinical Sciences, Immunology, Public Health and Health Services, Arthritis & Rheumatology, Clinical sciences
Abstract

ObjectiveAmerican Indian-Europeans, Asians, and African Americans have an excess morbidity from systemic lupus erythematosus (SLE) and a higher prevalence of lupus nephritis than do Caucasians. The aim of this study was to analyze the relationship between genetic ancestry and sociodemographic characteristics and clinical features in a large cohort of American Indian-European SLE patients.MethodsA total of 2,116 SLE patients of American Indian-European origin and 4,001 SLE patients of European descent for whom we had clinical data were included in the study. Genotyping of 253 continental ancestry-informative markers was performed on the Illumina platform. Structure and Admixture software were used to determine genetic ancestry proportions of each individual. Logistic regression was used to test the association between genetic ancestry and sociodemographic and clinical characteristics. Odds ratios (ORs) were calculated with 95% confidence intervals (95% CIs).ResultsThe average American Indian genetic ancestry of 2,116 SLE patients was 40.7%. American Indian genetic ancestry conferred increased risks of renal involvement (P < 0.0001, OR 3.50 [95% CI 2.63- 4.63]) and early age at onset (P < 0.0001). American Indian ancestry protected against photosensitivity (P < 0.0001, OR 0.58 [95% CI 0.44-0.76]), oral ulcers (P < 0.0001, OR 0.55 [95% CI 0.42-0.72]), and serositis (P < 0.0001, OR 0.56 [95% CI 0.41-0.75]) after adjustment for age, sex, and age at onset. However, age and sex had stronger effects than genetic ancestry on malar rash, discoid rash, arthritis, and neurologic involvement.ConclusionIn general, American Indian genetic ancestry correlates with lower sociodemographic status and increases the risk of developing renal involvement and SLE at an earlier age.

Published
2012

11. A genome-wide association search for type 2 diabetes genes in African Americans.

Author

Palmer, Nicholette D, McDonough, Caitrin W, Hicks, Pamela J, Roh, Bong H, Wing, Maria R, An, S Sandy, Hester, Jessica M, Cooke, Jessica N, Bostrom, Meredith A, Rudock, Megan E, Talbert, Matthew E, Lewis, Joshua P, DIAGRAM Consortium, MAGIC Investigators, Ferrara, Assiamira, Lu, Lingyi, Ziegler, Julie T, Sale, Michele M, Divers, Jasmin, Shriner, Daniel, Adeyemo, Adebowale, Rotimi, Charles N, Ng, Maggie CY, Langefeld, Carl D, Freedman, Barry I, Bowden, Donald W, Voight, Benjamin F, Scott, Laura J, Steinthorsdottir, Valgerdur, Morris, Andrew P, Dina, Christian, Welch, Ryan P, Zeggini, Eleftheria, Huth, Cornelia, Aulchenko, Yurii S, Thorleifsson, Gudmar, McCulloch, Laura J, Ferreira, Teresa, Grallert, Harald, Amin, Najaf, Wu, Guanming, Willer, Cristen J, Raychaudhuri, Soumya, McCarroll, Steve A, Langenberg, Claudia, Hofmann, Oliver M, Dupuis, Josée, Qi, Lu, Segrè, Ayellet V, van Hoek, Mandy, Navarro, Pau, Ardlie, Kristin, Balkau, Beverley, Benediktsson, Rafn, Bennett, Amanda J, Blagieva, Roza, Boerwinkle, Eric, Bonnycastle, Lori L, Boström, Kristina Bengtsson, Bravenboer, Bert, Bumpstead, Suzannah, Burtt, Noël P, Charpentier, Guillaume, Chines, Peter S, Cornelis, Marilyn, Couper, David J, Crawford, Gabe, Doney, Alex SF, Elliott, Katherine S, Elliott, Amanda L, Erdos, Michael R, Fox, Caroline S, Franklin, Christopher S, Ganser, Martha, Gieger, Christian, Grarup, Niels, Green, Todd, Griffin, Simon, Groves, Christopher J, Guiducci, Candace, Hadjadj, Samy, Hassanali, Neelam, Herder, Christian, Isomaa, Bo, Jackson, Anne U, Johnson, Paul RV, Jørgensen, Torben, Kao, Wen HL, Klopp, Norman, Kong, Augustine, Kraft, Peter, Kuusisto, Johanna, Lauritzen, Torsten, Li, Man, Lieverse, Aloysius, Lindgren, Cecilia M, Lyssenko, Valeriya, Marre, Michel, Meitinger, Thomas, and Midthjell, Kristian

Subjects
DIAGRAM Consortium, MAGIC Investigators, Humans, Diabetes Mellitus, Type 2, Genetic Predisposition to Disease, Case-Control Studies, Cohort Studies, Genotype, Polymorphism, Single Nucleotide, Adult, Aged, Middle Aged, African Americans, Female, Male, Meta-Analysis as Topic, Validation Studies as Topic, Genome-Wide Association Study, Diabetes Mellitus, Type 2, Polymorphism, Single Nucleotide, General Science & Technology
Abstract

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P

Published
2012

12. Effects of LRRK2 Inhibitors in Nonhuman Primates

Author

Miller, Glen K., primary, Kuruvilla, Sabu, additional, Jacob, Binod, additional, LaFranco-Scheuch, Lisa, additional, Bakthavatchalu, Vasudevan, additional, Flor, Jason, additional, Flor, Kristin, additional, Ziegler, Julie, additional, Reichard, Christine, additional, Manfre, Phil, additional, Firner, Suzanne, additional, McNutt, Tara, additional, Quay, Diane, additional, Bellum, Sairam, additional, Doto, Greg, additional, Ciaccio, Paul J., additional, Pearson, Kara, additional, Valentine, Jack, additional, Fuller, Pete, additional, Fell, Matt, additional, Tsuchiya, Takayuki, additional, Williamson, Toni, additional, and Wollenberg, Gordon, additional

Published
2023
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13. 1401 A Genome Wide Association Scan of SLE genetic risk in a cohort of African-American persons

Author

Harley, Isaac TW, primary, Sun, Celi, additional, Williams, Adrienne H, additional, Ziegler, Julie T, additional, Comeau, Mary E, additional, Marion, Miranda C, additional, Glenn, Stuart B, additional, Adler, Adam, additional, Frank-Pearce, Summer G, additional, Shen, Nan, additional, Kelly, Jennifer A, additional, Namjou-Khales, Bahram, additional, Petri, Michelle, additional, Alarcon-Riquelme, Marta, additional, Joseph McCune, W, additional, Gaffney, Patrick, additional, Sivils, Kathy, additional, Salmon, Jane E, additional, Weisman, Michael H, additional, Edberg, Jeffrey C, additional, Brown, Elizabeth E, additional, Utset, Tammy, additional, Criswell, Lindsey A, additional, Jacob, Chaim O, additional, Tsao, Betty, additional, Vyse, Timothy J, additional, James, Judith A, additional, Gilkeson, Gary S, additional, Kamen, Diane L, additional, Montgomery, Courtney, additional, Merrill, Joan T, additional, Nath, Swapan K, additional, Laurynenka, Viktoryia, additional, Chepelev, Iouri, additional, Harris-Lewis, Valerie, additional, Hal Scofield, R, additional, Kimberly, Robert P, additional, Langefeld, Carl D, additional, Harley, John B, additional, and Kaufman, Kenneth M, additional

Published
2022
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14. Identification of IRAK1 as a Risk Gene with Critical Role in the Pathogenesis of Systemic Lupus Erythematosus

Author

Jacob, Chaim O., Zhu, Jiankun, Armstrong, Don L., Yan, Mei, Han, Jie, Zhou, Xin J., Thomas, James A., Reiff, Andreas, Myones, Barry L., Ojwang, Joshua O., Kaufman, Kenneth M., Klein-Gitelman, Marisa, McCurdy, Deborah, Wagner-Weiner, Linda, Silverman, Earl, Ziegler, Julie, Kelly, Jennifer A., Merrill, Joan T., Harley, John B., Ramsey-Goldman, Rosalind, Vila, Luis M., Bae, Sang-Cheol, Vyse, Timothy J., Gilkeson, Gary S., Gaffney, Patrick M., Moser, Kathy L., Langefeld, Carl D., Zidovetzki, Raphael, Mohan, Chandra, and Vitetta, Ellen S.

Published
2009
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15. Genome-Wide Association Study in an Amerindian Ancestry Population Reveals Novel Systemic Lupus Erythematosus Risk Loci and the Role of European Admixture

Author

Alarcón-Riquelme, Marta E., Ziegler, Julie T., Molineros, Julio, Howard, Timothy D., Moreno-Estrada, Andrés, Sánchez-Rodríguez, Elena, Ainsworth, Hannah C., Ortiz-Tello, Patricia, Comeau, Mary E., Rasmussen, Astrid, Kelly, Jennifer A., Adler, Adam, Acevedo-Vázquez, Eduardo M., Mariano Cucho-Venegas, Jorge, García-De la Torre, Ignacio, Cardiel, Mario H., Miranda, Pedro, Catoggio, Luis J., Maradiaga-Ceceña, Marco, Gaffney, Patrick M., Vyse, Timothy J., Criswell, Lindsey A., Tsao, Betty P., Sivils, Kathy L., Bae, Sang-Cheol, James, Judith A., Kimberly, Robert P., Kaufman, Kenneth M., Harley, John B., Esquivel-Valerio, Jorge A., Moctezuma, José F., García, Mercedes A., Berbotto, Guillermo A., Babini, Alejandra M., Scherbarth, Hugo, Toloza, Sergio, Baca, Vicente, Nath, Swapan K., Aguilar Salinas, Carlos, Orozco, Lorena, Tusié-Luna, Teresa, Zidovetzki, Raphael, Pons-Estel, Bernardo A., Langefeld, Carl D., and Jacob, Chaim O.

Published
2016
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16. Preferential association of a functional variant in complement receptor 2 with antibodies to double-stranded DNA

Author

Zhao, Jian, Giles, Brendan M, Taylor, Rhonda L, Yette, Gabriel A, Lough, Kara M, Ng, Han Leng, Abraham, Lawrence J, Wu, Hui, Kelly, Jennifer A, Glenn, Stuart B, Adler, Adam J, Williams, Adrienne H, Comeau, Mary E, Ziegler, Julie T, Marion, Miranda, Alarcón-Riquelme, Marta E, Alarcón, Graciela S, Anaya, Juan-Manuel, Bae, Sang-Cheol, Kim, Dam, Lee, Hye-Soon, Criswell, Lindsey A, Freedman, Barry I, Gilkeson, Gary S, Guthridge, Joel M, Jacob, Chaim O, James, Judith A, Kamen, Diane L, Merrill, Joan T, Sivils, Kathy Moser, Niewold, Timothy B, Petri, Michelle A, Ramsey-Goldman, Rosalind, Reveille, John D, Scofield, R Hal, Stevens, Anne M, Vilá, Luis M, Vyse, Timothy J, Kaufman, Kenneth M, Harley, John B, Langefeld, Carl D, Gaffney, Patrick M, Brown, Elizabeth E, Edberg, Jeffrey C, Kimberly, Robert P, Ulgiati, Daniela, Tsao, Betty P, and Boackle, Susan A

Published
2016
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18. Increasing Diabetes Screening in a Primary Care Setting

Author

Iyengar, Jennifer J., primary, Fisher, Mary E.K., primary, Ziegler, Julie E., primary, Wright, Douglas W., primary, Monson, Meghan C., primary, Dehmlow, Cheryl L. Rhodes, primary, Schacht, Keturah P., primary, Wyckoff, Jennifer A., primary, and Fan, Audrey L., primary

Published
2021
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24. Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus

Author

Sanchez, Elena, Nadig, Ajay, Richardson, Bruce C, Freedman, Barry I, Kaufman, Kenneth M, Kelly, Jennifer A, Niewold, Timothy B, Kamen, Diane L, Gilkeson, Gary S, Ziegler, Julie T, Langefeld, Carl D, Alarcón, Graciela S, Edberg, Jeffrey C, Ramsey-Goldman, Rosalind, Petri, Michelle, Brown, Elizabeth E, Kimberly, Robert P, Reveille, John D, Vilá, Luis M, Merrill, Joan T, Anaya, Juan-Manuel, James, Judith A, Pons-Estel, Bernardo A, Martin, Javier, Park, So-Yeon, Bang, So-Young, Bae, Sang-Cheol, Moser, Kathy L, Vyse, Timothy J, Criswell, Lindsey A, Gaffney, Patrick M, Tsao, Betty P, Jacob, Chaim O, Harley, John B, Alarcón-Riquelme, Marta E, and Sawalha, Amr H

Published
2011
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25. Association of PPP2CA polymorphisms with systemic lupus erythematosus susceptibility in multiple ethnic groups

Author

Tan, Wenfeng, Sunahori, Katsue, Zhao, Jian, Deng, Yun, Kaufman, Kenneth M., Kelly, Jennifer A., Langefeld, Carl D., Williams, Adrienne H., Comeau, Mary E., Ziegler, Julie T., Marion, Miranda C., Bae, Sang-Cheol, Lee, Joo Hyun, Lee, Ji-Seon, Chang, Deh-Ming, Song, Yeong Wook, Yu, Chack-Yung, Kimberly, Robert P., Edberg, Jeffrey C., Brown, Elizabeth E., Petri, Michelle A., Ramsey-Goldman, Rosalind, Vilá, Luis M., Reveille, John D., Alarcón-Riquelme, Marta E., Harley, John B., Boackle, Susan A., Stevens, Anne M., Scofield, Hal R., Merrill, Joan T., Freedman, Barry I., Anaya, Juan-Manuel, Criswell, Lindsey A., Jacob, Chaim O., Vyse, Timothy J., Niewold, Timothy B., Gaffney, Patrick M., Moser, Kathy L., Gilkeson, Gary S., Kamen, Diane L., James, Judith A., Grossman, Jennifer M., Hahn, Bevra H., Tsokos, George C., and Tsao, Betty P.

Published
2011
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26. Genetic analyses of interferon pathway–related genes reveal multiple new loci associated with systemic lupus erythematosus

Author

Ramos, Paula S., Williams, Adrienne H., Ziegler, Julie T., Comeau, Mary E., Guy, Richard T., Lessard, Christopher J., Li, He, Edberg, Jeffrey C., Zidovetzki, Raphael, Criswell, Lindsey A., Gaffney, Patrick M., Graham, Deborah Cunninghame, Graham, Robert R., Kelly, Jennifer A., Kaufman, Kenneth M., Brown, Elizabeth E., Alarcón, Graciela S., Petri, Michelle A., Reveille, John D., McGwin, Gerald, Vilá, Luis M., Ramsey-Goldman, Rosalind, Jacob, Chaim O., Vyse, Timothy J., Tsao, Betty P., Harley, John B., Kimberly, Robert P., Alarcón-Riquelme, Marta E., Langefeld, Carl D., and Moser, Kathy L.

Published
2011
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27. Fine-mapping and transethnic genotyping establish IL2/IL21 genetic association with lupus and localize this genetic effect to IL21

Author

Hughes, Travis, Kim-Howard, Xana, Kelly, Jennifer A., Kaufman, Kenneth M., Langefeld, Carl D., Ziegler, Julie, Sanchez, Elena, Kimberly, Robert P., Edberg, Jeffrey C., Ramsey-Goldman, Rosalind, Petri, Michelle, Reveille, John D., Martín, Javier, Brown, Elizabeth E., Vilá, Luis M., Alarcón, Graciela S., James, Judith A., Gilkeson, Gary S., Moser, Kathy L., Gaffney, Patrick M., Merrill, Joan T., Vyse, Timothy J., Alarcón-Riquelme, Marta E., Nath, Swapan K., John B. Harley, and Sawalha, Amr H.

Published
2011
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30. A Polymorphism Within IL21R Confers Risk for Systemic Lupus Erythematosus

Author

Webb, Ryan, Merrill, Joan T., Kelly, Jennifer A., Sestak, Andrea, Kaufman, Kenneth M., Langefeld, Carl D., Ziegler, Julie, Kimberly, Robert P., Edberg, Jeffrey C., Ramsey-Goldman, Rosalind, Petri, Michelle, Reveille, John D., Alarcón, Graciela S., Vilá, Luis M., Alarcón-Riquelme, Marta E., James, Judith A., Gilkeson, Gary S., Jacob, Chaim O., Moser, Kathy L., Gaffney, Patrick M., Vyse, Timothy J., Nath, Swapan K., Lipsky, Peter, Harley, John B., and Sawalha, Amr H.

Published
2009
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32. High-density genotyping of STAT4 reveals multiple haplotypic associations with systemic lupus erythematosus in different racial groups

Author

Namjou, Bahram, Sestak, Andrea L., Armstrong, Don L., Zidovetzki, Raphael, Kelly, Jennifer A., Jacob, Noam, Ciobanu, Voicu, Kaufman, Kenneth M., Ojwang, Joshua O., Ziegler, Julie, Quismorio, Francesco P., Jr., Reiff, Andreas, Myones, Barry L., Guthridge, Joel M., Nath, Swapan K., Bruner, Gail R., Mehrian-Shai, Ruth, Silverman, Earl, Klein-Gitelman, Marisa, McCurdy, Deborah, Wagner-Weiner, Linda, Nocton, James J., Putterman, Chaim, Bae, Sang-Cheol, Kim, Yun Jung, Petri, Michelle, Reveille, John D., Vyse, Timothy J., Gilkeson, Gary S., Kamen, Diane L., Alarcón-Riquelme, Marta E., Gaffney, Patrick M., Moser, Kathy L., Merrill, Joan T., Scofield, Hal R., James, Judith A., Langefeld, Carl D., Harley, John B., and Jacob, Chaim O.

Published
2009
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35. Increasing Diabetes Screening in a Primary Care Setting.

Author

Iyengar, Jennifer J., Fisher, Mary E. K., Ziegler, Julie E., Wright, Douglas W., Monson, Meghan C., Rhodes Dehmlow, Cheryl L., Schacht, Keturah P., Wyckoff, Jennifer A., and Fan, Audrey L.

Subjects
DIAGNOSIS of diabetes, MEDICAL quality control, MEDICAL screening, PRIMARY health care, QUALITY assurance
Abstract

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes an initiative to increase rates of diabetes screening in a large multisite academic health system in the greater Ann Arbor, MI, area. [ABSTRACT FROM AUTHOR]

Published
2022
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45. Double-blinded randomized controlled trial of estrogen supplementation in adolescent in adolescent girls who receive depot medroxyprogesterone acetate for contraception

Author

Cromer, Barbara A., Rome, Ellen, Bonny, Andrea, Ziegler, Julie, Debanne, Sara M., Lazebnik, Rina, and Stager, Margaret

Subjects
Contraception -- Complications and side effects, Teenage pregnancy -- Research, Teenage pregnancy -- Drug therapy, Medroxyprogesterone -- Complications and side effects, Health
Abstract

The effect of estrogen supplementation on bone mineral density in adolescent girls who received depot medroxyprogesterone acetate for contraception is evaluated. The results suggest that estrogen supplementation is protective of bone in adolescent girls who receive depot medroxyprogesterone acetate injections.

Published
2005

46. Identification of ATPAF1 as a novel candidate gene for asthma in children

Author

Schauberger, Eric M., Ewart, Susan L., Arshad, Syed H., Huebner, Marianne, Karmaus, Wilfried, Holloway, John W., Friderici, Karen H., Ziegler, Julie T., Zhang, Hongmei, Rose-Zerilli, Matthew J., Barton, Sheila J., Holgate, Stephen T., Kilpatrick, Jeffrey R., Harley, John B., Lajoie-Kadoch, Stephane, Harley, Isaac T.W., Hamid, Qutayba, Kurukulaaratchy, Ramesh J., Seibold, Max A., Avila, Pedro C., Rodriguez-Cintrón, William, Rodriguez-Santana, Jose R., Hu, Donglei, Gignoux, Christopher, Romieu, Isabelle, London, Stephanie J., Burchard, Esteban G., Langefeld, Carl D., and Wills-Karp, Marsha

Published
2011

48. The impact of FADS genetic variants on ω6 polyunsaturated fatty acid metabolism in African Americans

Author

Rudock Megan E, Freedman Barry I, Yanek Lisa R, Case Douglas, Ivester Priscilla, Ziegler Julie T, Suktitipat Bhoom, Vaidya Dhananjay, Kubala Meghan, Hugenschmidt Christina E, Torgerson Dara G, Ruczinski Ingo, Sergeant Susan, Mathias Rasika A, Barnes Kathleen C, Langefeld Carl D, Becker Lewis C, Bowden Donald W, Becker Diane M, and Chilton Floyd H

Subjects
Genetics, QH426-470
Abstract

Abstract Background Arachidonic acid (AA) is a long-chain omega-6 polyunsaturated fatty acid (PUFA) synthesized from the precursor dihomo-gamma-linolenic acid (DGLA) that plays a vital role in immunity and inflammation. Variants in the Fatty Acid Desaturase (FADS) family of genes on chromosome 11q have been shown to play a role in PUFA metabolism in populations of European and Asian ancestry; no work has been done in populations of African ancestry to date. Results In this study, we report that African Americans have significantly higher circulating levels of plasma AA (p = 1.35 × 10-48) and lower DGLA levels (p = 9.80 × 10-11) than European Americans. Tests for association in N = 329 individuals across 80 nucleotide polymorphisms (SNPs) in the Fatty Acid Desaturase (FADS) locus revealed significant association with AA, DGLA and the AA/DGLA ratio, a measure of enzymatic efficiency, in both racial groups (peak signal p = 2.85 × 10-16 in African Americans, 2.68 × 10-23 in European Americans). Ancestry-related differences were observed at an upstream marker previously associated with AA levels (rs174537), wherein, 79-82% of African Americans carry two copies of the G allele compared to only 42-45% of European Americans. Importantly, the allelic effect of the G allele, which is associated with enhanced conversion of DGLA to AA, on enzymatic efficiency was similar in both groups. Conclusions We conclude that the impact of FADS genetic variants on PUFA metabolism, specifically AA levels, is likely more pronounced in African Americans due to the larger proportion of individuals carrying the genotype associated with increased FADS1 enzymatic conversion of DGLA to AA.

Published
2011
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49. A plausibly causal functional lupus-associated risk variant in the STAT1–STAT4 locus

Author

Patel, Zubin H, primary, Lu, Xiaoming, additional, Miller, Daniel, additional, Forney, Carmy R, additional, Lee, Joshua, additional, Lynch, Arthur, additional, Schroeder, Connor, additional, Parks, Lois, additional, Magnusen, Albert F, additional, Chen, Xiaoting, additional, Pujato, Mario, additional, Maddox, Avery, additional, Zoller, Erin E, additional, Namjou, Bahram, additional, Brunner, Hermine I, additional, Henrickson, Michael, additional, Huggins, Jennifer L, additional, Williams, Adrienne H, additional, Ziegler, Julie T, additional, Comeau, Mary E, additional, Marion, Miranda C, additional, Glenn, Stuart B, additional, Adler, Adam, additional, Shen, Nan, additional, Nath, Swapan K, additional, Stevens, Anne M, additional, Freedman, Barry I, additional, Pons-Estel, Bernardo A, additional, Tsao, Betty P, additional, Jacob, Chaim O, additional, Kamen, Diane L, additional, Brown, Elizabeth E, additional, Gilkeson, Gary S, additional, Alarcón, Graciela S, additional, Martin, Javier, additional, Reveille, John D, additional, Anaya, Juan-Manuel, additional, James, Judith A, additional, Sivils, Kathy L, additional, Criswell, Lindsey A, additional, Vilá, Luis M, additional, Petri, Michelle, additional, Scofield, R Hal, additional, Kimberly, Robert P, additional, Edberg, Jeffrey C, additional, Ramsey-Goldman, Rosalind, additional, Bang, So-Young, additional, Lee, Hye-Soon, additional, Bae, Sang-Cheol, additional, Boackle, Susan A, additional, Cunninghame Graham, Deborah, additional, Vyse, Timothy J, additional, Merrill, Joan T, additional, Niewold, Timothy B, additional, Ainsworth, Hannah C, additional, Silverman, Earl D, additional, Weisman, Michael H, additional, Wallace, Daniel J, additional, Raj, Prithvi, additional, Guthridge, Joel M, additional, Gaffney, Patrick M, additional, Kelly, Jennifer A, additional, Alarcón-Riquelme, Marta E, additional, Langefeld, Carl D, additional, Wakeland, Edward K, additional, Kaufman, Kenneth M, additional, Weirauch, Matthew T, additional, Harley, John B, additional, and Kottyan, Leah C, additional

Published
2018
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50. Transethnic Evaluation Identifies Low-Frequency Loci Associated With 25-Hydroxyvitamin D Concentrations

Author

Hong, Jaeyoung, primary, Hatchell, Kathryn E, additional, Bradfield, Jonathan P, additional, Bjonnes, Andrew, additional, Chesi, Alessandra, additional, Lai, Chao-Qiang, additional, Langefeld, Carl D, additional, Lu, Lingyi, additional, Lu, Yingchang, additional, Lutsey, Pamela L, additional, Musani, Solomon K, additional, Nalls, Mike A, additional, Robinson-Cohen, Cassianne, additional, Roizen, Jeffery D, additional, Saxena, Richa, additional, Tucker, Katherine L, additional, Ziegler, Julie T, additional, Arking, Dan E, additional, Bis, Joshua C, additional, Boerwinkle, Eric, additional, Bottinger, Erwin P, additional, Bowden, Donald W, additional, Gilsanz, Vicente, additional, Houston, Denise K, additional, Kalkwarf, Heidi J, additional, Kelly, Andrea, additional, Lappe, Joan M, additional, Liu, Yongmei, additional, Michos, Erin D, additional, Oberfield, Sharon E, additional, Palmer, Nicholette D, additional, Rotter, Jerome I, additional, Sapkota, Bishwa, additional, Shepherd, John A, additional, Wilson, James G, additional, Basu, Saonli, additional, de Boer, Ian H, additional, Divers, Jasmin, additional, Freedman, Barry I, additional, Grant, Struan F A, additional, Hakanarson, Hakon, additional, Harris, Tamara B, additional, Kestenbaum, Bryan R, additional, Kritchevsky, Stephen B, additional, Loos, Ruth J F, additional, Norris, Jill M, additional, Norwood, Arnita F, additional, Ordovas, Jose M, additional, Pankow, James S, additional, Psaty, Bruce M, additional, Sanghera, Dharambir K, additional, Wagenknecht, Lynne E, additional, Zemel, Babette S, additional, Meigs, James, additional, Dupuis, Josée, additional, Florez, Jose C, additional, Wang, Thomas, additional, Liu, Ching-Ti, additional, Engelman, Corinne D, additional, and Billings, Liana K, additional

Published
2018
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