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101. FUNCTIONAL AND ASSOCIATION ANALYSIS OF FRIZZLED 1 (FZD1) PROMOTER HAPLOTYPES WITH FEMORAL NECK GEOMETRY

Author

Laura M. Yerges-Armstrong, Allison L. Kuipers, Victor W. Wheeler, Alan L. Patrick, Cara S. Nestlerode, Joseph M. Zmuda, Zhao Jin, Clareann H. Bunker, and Yingze Zhang

Subjects
FZD1, Adult, Male, Histology, Physiology, Endocrinology, Diabetes and Metabolism, Blotting, Western, Single-nucleotide polymorphism, Geometry, Electrophoretic Mobility Shift Assay, Biology, Polymorphism, Single Nucleotide, Article, Cell Line, Gene Frequency, Bone Density, Surveys and Questionnaires, Humans, Electrophoretic mobility shift assay, Nuclear protein, Transversion, Promoter Regions, Genetic, Allele frequency, Alleles, Cells, Cultured, Genetic Association Studies, Genetics, Osteoblasts, Femur Neck, Reverse Transcriptase Polymerase Chain Reaction, Patient Selection, Haplotype, Promoter, Middle Aged, Molecular biology, Frizzled Receptors, Haplotypes
Abstract

Frizzleds are receptors for Wnt signaling and are involved in skeletal morphogenesis. Little is known about the transcriptional regulation of frizzleds in bone cells. In the current study, we determined if two common and potentially functional genetic variants (rs2232157, rs2232158) in the frizzled-1 (FZD1) promoter region and their haplotypes influence FZD1 promoter activity in human osteoblast-like cells. We also determined if these variants are associated with femoral neck bone mineral density (BMD) and geometry in 1319 African ancestry men agedor =40 years. Real-time quantitative PCR and western blot analysis demonstrated FZD1 mRNA and protein expression in the human osteoblast-like cell lines, MG63 and SaOS-2. Promoter activity was next assessed by transient expression of haplotype specific FZD1 promoter reporter plasmids in these cells. In comparison to the common GG haplotype, promoter activity was 3-fold higher for the TC haplotype in both cell lines (p0.05). We previously demonstrated that rs2232158 is associated with differential FZD1 promoter activity and Egr1 binding and thus focused further functional analyses on the rs2232157 G-to-T polymorphism. Electrophoretic mobility shift assay demonstrated that distinct nuclear protein complexes were associated with rs2232157 in an allele specific manner. Bioinformatics analysis predicted that the G to T transversion creates an E2F1 binding site, further supporting the functional significance of rs2232157 in FZD1 promoter regulation. Individual SNPs and haplotypes were not associated with femoral neck BMD. The TC haplotype was associated with larger subperiosteal width and greater CSMI (p0.05). These results suggest that FZD1 expression is regulated in a haplotype-dependent manner in osteoblasts and that these same haplotypes may be associated with biomechanical indices of bone strength.

Published
2010

102. Molecular Variation in Neuropeptide Y and Bone Mineral Density Among Men of African Ancestry

Author

Cara S. Nestlerode, Joseph M. Zmuda, Laura M. Yerges-Armstrong, Allison L. Kuipers, Iva Miljkovic, Louis J. Goodrich, Victor W. Wheeler, Alan L. Patrick, and Clareann H. Bunker

Subjects
Adult, Male, medicine.medical_specialty, Candidate gene, Linkage disequilibrium, Bone density, Genotype, Endocrinology, Diabetes and Metabolism, Population, Black People, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, Linkage Disequilibrium, Body Mass Index, Endocrinology, Bone Density, Internal medicine, medicine, Humans, Orthopedics and Sports Medicine, Neuropeptide Y, education, Bone mineral, education.field_of_study, Genetic Variation, Exons, Middle Aged, Neuropeptide Y receptor, Body Height, Body Composition, Body mass index
Abstract

Neuropeptide Y (NPY) is a physiological candidate gene for the regulation of body weight and has more recently been implicated in regulating bone mass. The current study sought to test if inherited variation in NPY might influence BMD in a population of African-ancestry men who have high bone mineral density (BMD). We genotyped 17 tagging single-nucleotide polymorphisms (SNPs) across the NPY gene region in 1,113 randomly selected men of African ancestry aged ≥40 years and tested for association with anthropometric characteristics and proximal femur BMD. The homozygous rare genotype of four SNPs was associated with a 0.92–1.59% decrease in stature (corrected P < 0.05). No SNP was associated with body mass index or body weight. Two SNPs in a 5-kb linkage disequilibrium block encompassing exons 3 and 4 were associated with proximal femur BMD, adjusted for age, body weight, and height (corrected P < 0.05). These results suggest that genetic variation at the NPY locus may contribute to bone density, independently of body weight.

Published
2009

103. The 7Q31 locus, containing WNT16, is associated with bone mineral density, osteoporotic fracture and bone strength

Author

Scott Wilson, Richard L. Prince, Mattias Lorentzon, Geoffrey C. Nicholson, Graeme Jones, Martin Ladouceur, David Goltzman, Emma L. Duncan, Hou-Feng Zheng, Paul Leo, John A. Eisman, Patrick Danoy, Liesbeth Vandenput, Elizabeth A. Streeten, Laura M. Yerges-Armstrong, Jeff Liu, William D. Leslie, Robert Brommage, Eugene V. McCloskey, Elaine M. Dennison, Ulrika Pettersson, Yongjun Xiao, Matthew A. Brown, P. N. Sambrook, Claes Ohlsson, Ian R. Reid, J. B. Richards, Ulrica Bergström, Braxton D. Mitchell, Johan G. Eriksson, Tim D. Spector, and R. Eastell

Subjects
Bone mineral, animal structures, Histology, Physiology, business.industry, Endocrinology, Diabetes and Metabolism, Osteoporosis, Dentistry, Locus (genetics), medicine.disease, Bone strength, medicine.anatomical_structure, Forearm, medicine, Osteoporotic fracture, business
Abstract

The 7Q31 locus, containing WNT16, is associated with bone mineral density, osteoporotic fracture and bone strength

Published
2012
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104. Pharmacometabolomics Reveals That Serotonin Is Implicated in Aspirin Response Variability

Author

Cynthia M. Kuhn, Rima Kaddurah-Daouk, Hongjie Zhu, R. Ramaker, Thomas L. Ortel, Rob J. Vreeken, Adrie Dane, Thomas Hankemeier, Anastasia Georgiades, Christina G. Perry, Joshua P. Lewis, Amber L. Beitelshees, Amy C. Harms, Richard B. Horenstein, Sandrine Ellero-Simatos, Laura M. Yerges-Armstrong, C. L. Sánchez, Alan R. Shuldiner, Hankemeier, Thomas, Kaddurah-Daouk, R, Leiden University, University of Maryland School of Medecine, Partenaires INRAE, Duke University Medical Center, RWTH Aachen University, Department of Psychiatry and Behavioral Sciences, and Duke University [Durham]

Subjects
0303 health sciences, Aspirin, business.industry, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Pharmacology, Response Variability, 3. Good health, Platelet reactivity, 03 medical and health sciences, 0302 clinical medicine, Modeling and Simulation, Cohort, Medicine, Original Article, Pharmacology (medical), Platelet, Serotonin, business, Incubation, Ex vivo, 030304 developmental biology, medicine.drug
Abstract

International audience; While aspirin is generally effective for prevention of cardiovascular disease, considerable variation in drug response exists, resulting in some individuals displaying high on-treatment platelet reactivity. We used pharmacometabolomics to define pathways implicated in variation of response to treatment. We profiled serum samples from healthy subjects pre- and postaspirin (14 days, 81 mg/day) using mass spectrometry. We established a strong signature of aspirin exposure independent of response (15/34 metabolites changed). In our discovery (N = 80) and replication (N = 125) cohorts, higher serotonin levels pre- and postaspirin correlated with high, postaspirin, collagen-induced platelet aggregation. In a third cohort, platelets from subjects with the highest levels of serotonin preaspirin retained higher reactivity after incubation with aspirin than platelets from subjects with the lowest serotonin levels preaspirin (72 ± 8 vs. 61 ± 11%, P = 0.02, N = 20). Finally, ex vivo, serotonin strongly increased platelet reactivity after platelet incubation with aspirin (+20%, P = 4.9 × 10−4, N = 12). These results suggest that serotonin is implicated in aspirin response variability.

Published
2014
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105. 697 Novel Approach Reveals That Genetic Variation in/Near FXR/RXR Pathway Genes Predisposes to Nonalcoholic Fatty Liver Disease in Humans

Author

Patricia A. Peyser, Ingrid B. Borecki, Tamara B. Harris, Laura M. Yerges-Armstrong, Corey Powell, Lawrence F. Bielak, Solomon K. Musani, Elizabeth K. Speliotes, Yindra Puentes, Albert V. Smith, and Mary F. Feitosa

Subjects
chemistry.chemical_classification, medicine.medical_specialty, Hepatology, Fatty liver, Gastroenterology, Fatty acid, Caspase 3, medicine.disease, Molecular biology, Endocrinology, medicine.anatomical_structure, Lipotoxicity, chemistry, Internal medicine, Hepatocyte, medicine, Unfolded protein response, Steatosis, Toyocamycin
Abstract

Background and Aim: Free fatty acid-induced hepatocyte cytotoxicity is deeply associated withmorbidity of Non-alcoholic fatty liver disease (NAFLD) (Malhi et al, 2008, Gastroenterology). Saturated free fatty acids induce hepatocyte lipoapoptosis via endoplasmic reticulum stress (ER) response, which leads to translational activation of DR5 and BH3 only protein Bim (Cazanave et al, JBC, 2011). We previously reported that X-box binding protein-1 (XBP-1) is activated downstream of IRE-1 arm of ER stress by free fatty acid treatment upon its splicing (Akazawa et al, 2009, J Hepatol). However, role of XBP-1 during hepatocyte lipoapoptosis remains relatively unexplored. We examined the impact of inhibiting XBP-1 on hepatocyte lipoapoptosis and steatosis employing Toyocamycin, which was recently reported to inhibit ER stress-mediated XBP-1 splicing (Ri M et al, Blood Cancer J. 2012). Methods: We employed hepatocellular carcinoma cell line, Huh-7 cells, for these studies. Cells were incubated with palmitate (200~800μM) in presence or absence of Toyocamycin (0.1~3μM). Apoptosis was assessed by DAPI staining and caspase 3/7 activity assay. Steatosis was assessed by Nile red staining. mRNA expression of Bim and DR5 was examined by real time PCR. Expression of Bim protein and phosphorylation of JNK was assessed by immunoblotting. Results: As expected, Toyocamycin inhibited palmitate-mediated XBP-1 splicing without affecting amount of total RNA. Toyocamycin significantly reduced palmitateinduced hepatocyte lipoapoptosis (p

Published
2014
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106. Genetic association analysis of radiographic hip osteoarthritis with established loci for bone mineral density: data from the osteoarthritis initiative

Author

Michael C. Nevitt, Pia M. Jungmann, Nancy E Lane, Braxton D. Mitchell, Michelle S. Yau, Rebecca D. Jackson, Laura M. Yerges-Armstrong, Marc C. Hochberg, and David Duggan

Subjects
education.field_of_study, medicine.medical_specialty, RHOA, biology, business.industry, Population, Biomedical Engineering, Case-control study, Single-nucleotide polymorphism, FGF18, Osteoarthritis, medicine.disease, Rheumatology, Endocrinology, Internal medicine, biology.protein, medicine, Orthopedics and Sports Medicine, Allele, education, business
Abstract

s / Osteoarthritis and Cartilage 22 (2014) S57–S489 S234 Results: Common among all impacted groups in comparison to CTRL groups at every time point was the increased gene expression associated with the IPA canonical pathway/functional category “Role of Osteoblasts, osteoclasts and chondrocytes in Rheumatoid arthritis” containing genes such as BMP2, BMP4, MMP13, FRZB, TNSF11, and ITGP3 . The biological networks associated with impacts differed with impact magnitude and time. After 24 hours, gene networks associated with “Skeletal and Muscular system development and function, tissue development, connective tissue disorders” (MATN3, MMP13, FGF18, DMP1, BMP2, BMP4, COL9A1, TGFB3, etc.) were active after 17 MPa impacts as compared to the biological network “Cellular development, Cellular growth and proliferation, Skeletal and muscular system development and function” (COL10A1, VCAN, WISP1, TGFB3, etc.) which was differentially expressed after 36 MPa impacts. 36 MPa impacts also changed the expression of genes in the “Granulocyte adhesion and diapedesis” (CCL20, CXCL14, CXCR2, PECAM1, etc.) functional category indicating a greater inflammatory response. Three days after impact, both impact groups showed differential expression of genes in the “Cell cycle, Cellular Assembly and organization, DNA replication, recombination and repair” group represented by genes such as CDK1, CENPE, CENPF, MATN3, among others. Similar biological groups were also identified 7 days after impact in the 17 MPa group with representative genes such as BMP4, MMP13, OMD, COL10A1, COL1A1, and DMP1. In the 7-day, 36 MPa group, we observed markers such as IBSP, BAMBI, FGF7, SP7, and POSTN. Conclusions: While we observed differential expression of catabolic genes such as MMP13, MMP3 and anabolic genes like COL2A1, COL1A1, and MATN3 in most impact groups and time points, we found that each condition was also characterized by the expression of specific sets of genes. 24 hours after impact we noticed the expression of proinflammatory genes (e.g. IL-6) following the high impact force. Three days following impact, the top functional pathway identified by IPA in both the 17MPa and the 36MPa groups contained genes involved in cell cycle and DNA repair, suggesting the activation of a common reparatory mechanism. At 7 days gene expression by cells in 17 and 36 MPa impact samples diverged between chondrogenic/hypertrophic and osteogenic functional groups. This difference may reflect a more advanced disease state in the high impact group, or a different response altogether. Many of the genes identified in this study were previously identified as markers of OA, indicating that further validation and functional analyses of novel loci identified here could lead to the development of new PT-OA therapeutic candidates. 416 GENETIC ASSOCIATION ANALYSIS OF RADIOGRAPHIC HIP OSTEOARTHRITIS WITH ESTABLISHED LOCI FOR BONE MINERAL DENSITY: DATA FROM THE OSTEOARTHRITIS INITIATIVE L.M. Yerges-Armstrong y, M.C. Nevitt z, M.S. Yau y, N.E. Lane x, D.J. Duggan k, P.M. Jungmann{, B.D. Mitchell y, R.D. Jackson#, M.C. Hochberg y. yUniv. of Maryland, Baltimore, MD, USA; zUniv. of California, San Francisco, CA, USA; xUniv. of California, Davis, CA, USA; k Translational Genomics Res. Inst., Phoenix, AZ, USA; { Technical Univ. of Munich, Munich, Germany; # The Ohio State Univ., Columbus, OH, USA Purpose: Previous studies have shown that high bone mineral density (BMD) is associated with an increased risk of knee and hip osteoarthritis. We recently completed an analysis evaluating the association of 56 established BMD loci (64 SNPs) for their association with radiographic knee osteoarthritis (rKOA) and identified four genetic variants associated with higher BMD that were also associated with higher odds of rKOA. With this in mind we conducted genetic association analysis to determine the relationship between these 56 BMD loci and radiographic hip osteoarthritis (rHOA). Methods: The current analysis was conducted on European-American participants from the Osteoarthritis Initiative with genome wide genotyping (Illumina 2.5 M array) and pelvis radiographs obtained at the baseline and 48 month visits. Pelvis images were read for radiographic features (IRFs) of hip OA using the OARSI atlas, and hips were classified as definite rHOA (Croft grade 2 or definite osteophytes or definite JSN), possible rHOA (IRFs present but not definite, e.g. isolated grade 1 osteophyte or joint space narrowing) or normal. Cases had at least one hip with definite rHOA at either time-point and hips replaced during follow-up with an adjudicated diagnosis of OA or degenerative arthritis. Controls had bilateral normal hips at baseline and, if radiographs were available, at 48 month follow-up. Using these definitions we identified 350 cases and 2294 controls with genotyping data for analysis. In two sensitivity analyses we included subjects with possible RHOA as cases and used as controls only those who had a 48-month pelvis films. Association analyses included adjustments for age, gender, BMI and principal components to correct for fine-scale population substructure. Results:We identified one variant (rs7217932) near the SOX9 locus that had a nominal association with rHOA (p 1⁄4 0.03, OR 1⁄4 1.20). The allele associated with higher BMD was associated with higher odds of rHOA. Of note, this variant was one of the few BMD loci associated with BMD in the hip (femoral neck) but not the lumbar spine. The association did not remain significant when subjects with possible OAwere included as cases (p 1⁄4 0.13, OR 1⁄4 1.10) but did when we required 48-month images for controls (p 1⁄4 0.05 OR 1⁄4 1.18). None of the SNPs we identified from our association analysis of rKOA were associated with rHOA (p > 0.05). A BMD risk allele score based on 62 independent loci was not significantly associated with rHOA risk. Conclusions: Despite a limited sample size we identified a nominal association between a variant associated with femoral neck BMD and rHOA, however this association does not remain significant after accounting for multiple testing. Replication analysis in additional cohorts is needed to confirm these findings, however the SOX9 locus may play a role in osteoarthritis in addition to BMD at the hip. 417 LSD1-MEDIATED DEMETHYLATION OF HISTONE H3 LYSINE 9 CONTRIBUTES TO INTERLEUKIN 1-INDUCED MICROSOMAL PROSTAGLANDIN E SYNTHASE-1 EXPRESSION IN HUMAN OSTEOARTHRITIC CHONDROCYTES F-E. El Mansouri, S-S. Nebbaki, H. Afif, M. Kapoor, J. Martrel-Pelletier, J-P. Pelletier, M. Benderdour, H. Fahmi. CRCHUM, Univ. of Montreal, Montreal, QC, Canada Purpose: Microsomal prostaglandin E synthase-1 catalyzes the terminal step in the biosynthesis of PGE2, which plays a critical role in the pathophysiology of osteoarthritis. To investigate the role of histone H3 (H3K9) methylation in interleukin-1b (IL-1)-induced microsomal prostaglandin E synthase-1 (mPGES-1) expression in human osteoarthritic (OA) chondrocytes. Methods: Chondrocytes were stimulated with IL-1 and the expression of mPGES-1mRNA was analyzed using real-time reverse transcriptasepolymerase chain reaction. H3K9 methylation and the recruitment of the histone demethylase LSD1 to the mPGES-1 promoter were evaluated using chromatin immunoprecipitation assays. The role of LSD1 was further evaluated using the the amino oxidase inhibitor tranylcypromine (a potent inhibitor of LSD1 activity). Results: Treatment with IL-1 induced mPGES-1 expression in a time dependent manner. The induction of mPGES-1 expression by IL-1 was associated with H3K9 demethylation at the mPGES-1 promoter. These changes were concomitant with the recruitment of the histone demethylase LSD1. Treatment with tranylcypromine inhibited IL-1-induced H3K9 demethylation as well as IL-1-induced mPGES-1 expression. Conclusions: These results indicate that H3K9 demethylation by LSD1 contributes to IL-1-induced mPGES-1 expression and suggest that this pathway could be a potential target for pharmacological intervention in the treatment of OA and possibly other arthritic diseases. 418 A CASE CONTROL STUDY TO EVALUATE THE ROLE OF GENETIC AND ENVIRONMENTAL RISK FACTOR IN DEVELOPMENT AND PROGRESSION OF OSTEOARTHRITIS KNEE A. Mishra, D. Sanghi, A.C. Sharma, R.N. Srivastava. King George’s.Med. Univ., Lucknow, India Purpose: The present study was initiated to investigate the interaction of SNPs in Estrogen receptor-a (ESR-a), Calmodulin-1 (CALM-1) and Growth differentiation factor-5 (GDF-5) gene with osteoarthritis knee (KOA); correlation of these genetic variants with envoirmnental factor such as living standards and occupation. Methodology: In a case-control study, 300 cases with KOA and an equal number of age matched healthy controls were included. Cases were diagnosed using the American College of Rheumatology (ACR) guidelines of knee osteoarthritis (KOA). Blood was drawn for genomic DNA isolation; polymerase chain reaction coupled restriction fragments length polymorphism (PCR-RFLP), TaqMan assay were carried out to

Published
2014
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107. Front and Back Matter

Author

Katherine Montague, Fotios Drenos, Holger Schwender, Ingrid B. Borecki, Elizabeth K. Speliotes, Alexis Gorden, Alex Luedtke, Kathleen A. Ryan, G. Craig Wood, Satz Mengensatzproduktion, Shumei Sun, Nianjun Liu, Qizhai Li, Druck Reinhardt Druck Basel, Ingo Ruczinski, Christopher D. Still, Gie Ken-Dror, Steve E. Humphries, Guimin Gao, Derek Gordon, Laura M. Yerges-Armstrong, Alan R. Shuldiner, Nathan L. Tintle, Thomas A. Louis, Rongze Yang, Wenan Chen, Glenn S. Gerhard, Xiangning Chen, Zhongming Zhao, Tamara B. Harris, Xin Chu, Qing Li, Kellie J. Archer, M. Daniele Fallin, and Keli Liu

Subjects
Optics, business.industry, Genetics, business, Genetics (clinical), Geology, Front (military)
Published
2013
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108. Racial differences in pain reporting in subjects with OR at risk for symptomatic radiographic knee osteoarthritis: data from the osteoarthritis initiative

Author

Braxton D. Mitchell, Marc C. Hochberg, Laura M. Yerges-Armstrong, and P. Luneburg

Subjects
medicine.medical_specialty, Rheumatology, business.industry, Radiography, Biomedical Engineering, Physical therapy, Medicine, Orthopedics and Sports Medicine, Racial differences, Osteoarthritis, business, medicine.disease
Published
2012
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109. A genetic analysis of osteoarthritis of the knee in north american caucasians: results from the osteoarthritis initiative and Johnston County osteoarthritis project

Author

W.J. Mysiw, Jordan B. Renner, Darin Taverna, Rebecca D. Jackson, Braxton D. Mitchell, Laura M. Yerges-Armstrong, Joanne M. Jordan, David Duggan, Marc C. Hochberg, T. McSherry, and C. Lu

Subjects
musculoskeletal diseases, medicine.medical_specialty, business.industry, Biomedical Engineering, Single-nucleotide polymorphism, Osteoarthritis, medicine.disease, Genetic analysis, Rheumatology, Chromosome regions, Internal medicine, Physical therapy, Medicine, Orthopedics and Sports Medicine, business
Abstract

senting 54 different chromosome regions, were suggestively associated with knee OA at a threshold of P < 10 -4 . We then tested these SNPs for association with knee OA in cases and controls from the JoCo Study. Of the 87 SNPs available for replication in JoCo, none were significantly associated with knee OA at a nominal P < 0.01. At our tested levels of significance (i.e., P < 10

Published
2012
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110. Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche

Author

Jing Hua Zhao, Vilmundur Gudnason, Robin Haring, Enda M. Byrne, Christian Gieger, Marek Zygmunt, Lude Franke, Peter Kraft, Eric Boerwinkle, Matthias W. Beckmann, Catharina A. Hartman, Thorkild I. A. Sørensen, Aida Karina Dieffenbach, André G. Uitterlinden, Grant W. Montgomery, Graham G. Giles, Felix R. Day, Anja Rudolph, Arto Mannermaa, Sven Bergmann, Nora Franceschini, Julian Peto, Ellen W. Demerath, Diana L. Cousminer, Wei Ang, Gudmar Thorleifsson, Patrick F. McArdle, Dieter Flesch-Janys, Albertine J. Oldehinkel, Irene L. Andrulis, Aarno Palotie, Nicholas J. Timpson, Paolo Peterlongo, Johan G. Eriksson, Bernardo Bonanni, Dorret I. Boomsma, J. Margriet Collée, Immaculata De Vivo, Bjarke Feenstra, Teresa Ferreira, Cornelia M. van Duijn, Nancy L. Pedersen, Deborah J. Thompson, Peter Vollenweider, Douglas F. Easton, Pascal Guénel, Anna Maria Storniolo, Erik Ingelsson, Gisli Masson, Annika Lindblom, Stefania Bandinelli, Elisabeth Widen, Doris Stöckl, Veikko Salomaa, Zoltán Kutalik, Nicholas J. Wareham, Joanne M. Murabito, Eleonora Porcu, Fergus J. Couch, Katri Pylkäs, Luigi Ferrucci, Wendy L. McArdle, Frank Geller, Andrea D. Coviello, Lynda M. Rose, Daniel L. Koller, Ute Hamann, Ulla Sovio, Daniel F. Gudbjartsson, Georgia Chenevix-Trench, Roger L. Milne, Unnur Thorsteinsdottir, Paul M. Ridker, Henry Völzke, John R. B. Perry, Stephen J. Chanock, Tanguy Corre, Mads Melbye, Ben A. Oostra, Albert V. Smith, Tõnu Esko, Melissa E. Garcia, Debbie A Lawlor, Meir J. Stampfer, Per Hall, Patrick Sulem, Massimo Mangino, Nicholas G. Martin, David J. Hunter, Laura Crisponi, Tatiana Foroud, Antonietta Robino, Michael J. Econs, Susan M. Ring, Natalia Tšernikova, Dirkje S. Postma, Lavinia Paternoster, Peter A. Fasching, Tamara B. Harris, Ellen A. Nohr, Javier Benitez, Ruth J. F. Loos, Robert Winqvist, Andres Metspalu, Jenny A. Visser, Heather A. Boyd, Jonathan Tyrer, Alexander Teumer, Tim D. Spector, Sandra Lai, Douglas P. Kiel, Kamila Czene, Hiltrud Brauch, George Davey Smith, Julia A. Knight, Erin K. Wagner, Suiqun Guo, Tune H. Pers, Patrik K. E. Magnusson, Kathryn L. Lunetta, Hoda Anton-Culver, Marjanka K. Schmidt, George McMahon, Ken K. Ong, Adamo Pio D'Adamo, Veli-Matti Kosma, Jinhui Chen, Paul D.P. Pharoah, Diether Lambrechts, Femke Atsma, Serena Sanna, Ilja M. Nolte, Eco de Geus, Daniel I. Chasman, Emmi Tikkanen, John L. Hopper, Anna Murray, Laura M. Yerges-Armstrong, Sanela Kjellqvist, Eva Albrecht, Hermann Brenner, Paolo Gasparini, Bruce H. R. Wolffenbuttel, Alison M. Dunning, John P. Rice, Craig E. Pennell, Mark I. McCarthy, Andrea Ganna, Henri Wallaschofski, Frank B. Hu, Gérard Waeber, Henrik Flyger, Evelin Mihailov, Peter Devilee, Lisette Stolk, Behrooz Z. Alizadeh, Jouke-Jan Hottenga, Najaf Amin, Patrick Neven, Reedik Mägi, Kyriaki Michailidou, Kari Stefansson, Munro Peacock, Julie E. Buring, Laura J. Bierut, Cathy E. Elks, Marjo-Riitta Järvelin, Montserrat Garcia-Closas, Anneli Pouta, David Schlessinger, Harold Snieder, Chunyan He, Joe Dennis, Heli Nevanlinna, Gonneke Willemsen, Andrew C. Heath, Elizabeth A. Streeten, Albert Hofman, Angela Cox, Maartje J. Hooning, Lili Milani, Margaret J. Wright, Fernando Rivadeneira, Gudny Eiriksdottir, Mellissa C. Southey, Qin Wang, Paolo Radice, Manjeet K. Bolla, Kay-Tee Khaw, Carl Blomqvist, Melanie Waldenberger, Sheila Ulivi, David Couper, Jenny Chang-Claude, David Karasik, Stig E. Bojesen, Andrew D. Johnson, David P. Strachan, Perry, John [0000-0001-6483-3771], Day, Felix [0000-0003-3789-7651], Thompson, Deborah [0000-0003-1465-5799], Zhao, Jing Hua [0000-0003-4930-3582], Dennis, Joe [0000-0003-4591-1214], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Sovio, Ulla [0000-0002-0799-1105], Tyrer, Jonathan [0000-0003-3724-4757], Wang, Jean [0000-0002-9139-0627], Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Easton, Douglas [0000-0003-2444-3247], Ong, Kenneth [0000-0003-4689-7530], Apollo - University of Cambridge Repository, Australian Ovarian Cancer Study, GENICA Network, kConFab, LifeLines Cohort Study, InterAct Consortium, Early Growth Genetics (EGG) Consortium, Cousminer, D.L., Stergiakouli, E., Berry, D.J., Ang, W., Groen-Blokhuis, M.M., Körner, A., Siitonen, N., Ntalla, I., Marinelli, M., Perry, J.R., Kettunen, J., Jansen, R., Surakka, I., Timpson, N.J., Ring, S., McMahon, G., Power, C., Wang, C., Kähönen, M., Viikari, J., Lehtimäki, T., Middeldorp, C.M., Hulshoff Pol, H.E., Neef, M., Weise, S., Pahkala, K., Niinikoski, H., Zeggini, E., Panoutsopoulou, K., Bustamante, M., Penninx, B.W., Murabito, J., Torrent, M., Dedoussis, G.V., Kiess, W., Boomsma, D.I., Pennell, C.E., Raitakari, O.T., Hyppönen, E., Davey Smith, G., Ripatti, S., McCarthy, M.I., Widén, E., Alizadeh, B.Z., de Boer, R.A., Boezen, H.M., Bruinenberg, M., Franke, L., van der Harst, P., Hillege, H.L., van der Klauw, M.M., Navis, G., Ormel, J., Postma, D., Rosmalen, J.G., Slaets, J.P., Snieder, H., Stolk, R.P., Wolffenbuttel, B.H., Wijmenga, C., Forouhi, N., Kerrison, N.D., Langenberg, C., Scott, R.A., Sharp, S.J., Sims, M., Barroso, I., Deloukas, P., Arriola, L., Balkau, B., Barricarte, A., Boeing, H., Franks, P.W., Gonzalez, C., Grioni, S., Kaaks, R., Key, T.J., Navarro, C., Nilsson, P.M., Overvad, K., Palli, D., Panico, S., Quirós, J., Rolandsson, O., Sacerdote, C., Sánchez, M.J., Slimani, N., Tjonneland, A., Tumino, R., van der A, D.L., van der Schouw, Y.T., Riboli, E., Wareham, N.J., Bowtell, D.D., Green, A., Chenevix-Trench, G., deFazio, A., Gertig, D., Webb, P.M., Brauch, H., Justenhoven, C., Hamann, U., Ko, Y.D., Baisch, C., Fischer, H.P., Pesch, B., Rabstein, S., Spickenheuer, A., Harth, V., Aghmesheh, M., Amor, D., Andrews, L., Antill, Y., Armitage, S., Arnold, L., Balleine, R., Bankier, A., Bastick, P., Beesley, J., Beilby, J., Bennett, I., Bennett, B., Berry, G., Blackburn, A., Bogwitz, M., Brennan, M., Brown, M., Buckley, M., Burgess, M., Burke, J., Butow, P., Byron, K., Callen, D., Campbell, I., Chauhan, D., Christian, A., Clarke, C., Colley, A., Cotton, D., Crook, A., Cui, J., Culling, B., Cummings, M., Dawson, S.J., Delatycki, M., Dickson, R., Dixon, J., Dobrovic, A., Dudding, T., Edkins, T., Edwards, S., Eisenbruch, M., Farshid, G., Fawcett, S., Fellows, A., Fenton, G., Field, M., Firgaira, F., Flanagan, J., Fleming, J., Fong, P., Forbes, J., Fox, S., French, J., Friedlander, M., Gaff, C., Gardner, M., Gattas, M., George, P., Giles, G., Gill, G., Goldblatt, J., Greening, S., Grist, S., Eric, H., Hardie, K., Harris, M., Hart, S., Hayward, N., Healey, S., Heiniger, L., Hopper, J., Humphrey, E., Hunt, C., James, P., Jenkins, M., Jones, A., Kefford, R., Kidd, A., Kiely, B., Kirk, J., Koehler, J., Kollias, J., Kovalenko, S., Lakhani, S., Leaming, A., Leary, J., Lim, J., Lindeman, G., Lipton, L., Lobb, L., Mann, G., Marsh, D., McLachlan, S.A., Meiser, B., Meldrum, C., Milne, R., Mitchell, G., Newman, B., O'Connell, S., O'Loughlin, I., Osborne, R., Pachter, N., Patterson, B., Peters, L., Phillips, K., Price, M., Purser, L., Reeve, J., Reeve, T., Richards, R., Rickard, E., Robinson, B., Rudzki, B., Saleh, M., Salisbury, E., Sambrook, J., Saunders, C., Saunus, J., Sayer, R., Scott, E., Scott, R., Scott, C., Seshadri, R., Sexton, A., Sharma, R., Shelling, A., Simpson, P., Southey, M., Spurdle, A., Suthers, G., Sykes, P., Taylor, D., Taylor, J., Thierry, B., Thompson, E., Thorne, H., Townshend, S., Trainer, A., Tran, L., Tucker, K., Tyler, J., Visvader, J., Walker, L., Walpole, I., Waring, P., Warner, B., Warren, G., Williams, R., Wilson, J., Winship, I., Wu, K., Young, M.A., Public Health, Internal Medicine, Epidemiology, Clinical Genetics, Medical Oncology, Child and Adolescent Psychiatry / Psychology, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Groningen Research Institute for Asthma and COPD (GRIAC), Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, EMGO+ - Lifestyle, Overweight and Diabetes, Political Science, Perry, John R. B, Day, Felix, Elks, Cathy E, Sulem, Patrick, Thompson, Deborah J, Ferreira, Teresa, He, Chunyan, Chasman, Daniel I, Esko, Tõnu, Thorleifsson, Gudmar, Albrecht, Eva, Ang, Wei Q, Corre, Tanguy, Cousminer, Diana L, Feenstra, Bjarke, Franceschini, Nora, Ganna, Andrea, Johnson, Andrew D, Kjellqvist, Sanela, Lunetta, Kathryn L, Mcmahon, George, Nolte, Ilja M, Paternoster, Lavinia, Porcu, Eleonora, Smith, Albert V, Stolk, Lisette, Teumer, Alexander, Tšernikova, Natalia, Tikkanen, Emmi, Ulivi, Sheila, Wagner, Erin K, Amin, Najaf, Bierut, Laura J, Byrne, Enda M, Hottenga, Jouke Jan, Koller, Daniel L, Mangino, Massimo, Pers, Tune H, Yerges Armstrong, Laura M, Hua Zhao, Jing, Andrulis, Irene L, Anton Culver, Hoda, Atsma, Femke, Bandinelli, Stefania, Beckmann, Matthias W, Benitez, Javier, Blomqvist, Carl, Bojesen, Stig E, Bolla, Manjeet K, Bonanni, Bernardo, Brauch, Hiltrud, Brenner, Hermann, Buring, Julie E, Chang Claude, Jenny, Chanock, Stephen, Chen, Jinhui, Chenevix Trench, Georgia, Collée, J. Margriet, Couch, Fergus J, Couper, David, Coviello, Andrea D, Cox, Angela, Czene, Kamila, D'Adamo, Adamo Pio, Davey Smith, George, De Vivo, Immaculata, Demerath, Ellen W, Dennis, Joe, Devilee, Peter, Dieffenbach, Aida K, Dunning, Alison M, Eiriksdottir, Gudny, Eriksson, Johan G, Fasching, Peter A, Ferrucci, Luigi, Flesch Janys, Dieter, Flyger, Henrik, Foroud, Tatiana, Franke, Lude, Garcia, Melissa E, García Closas, Montserrat, Geller, Frank, de Geus, Eco E. J, Giles, Graham G, Gudbjartsson, Daniel F, Gudnason, Vilmundur, Guénel, Pascal, Guo, Suiqun, Hall, Per, Hamann, Ute, Haring, Robin, Hartman, Catharina A, Heath, Andrew C, Hofman, Albert, Hooning, Maartje J, Hopper, John L, Hu, Frank B, Hunter, David J, Karasik, David, Kiel, Douglas P, Knight, Julia A, Kosma, Veli Matti, Kutalik, Zoltan, Lai, Sandra, Lambrechts, Diether, Lindblom, Annika, Mägi, Reedik, Magnusson, Patrik K, Mannermaa, Arto, Martin, Nicholas G, Masson, Gisli, Mcardle, Patrick F, Mcardle, Wendy L, Melbye, Mad, Michailidou, Kyriaki, Mihailov, Evelin, Milani, Lili, Milne, Roger L, Nevanlinna, Heli, Neven, Patrick, Nohr, Ellen A, Oldehinkel, Albertine J, Oostra, Ben A, Palotie, Aarno, Peacock, Munro, Pedersen, Nancy L, Peterlongo, Paolo, Peto, Julian, Pharoah, Paul D. P, Postma, Dirkje S, Pouta, Anneli, Pylkäs, Katri, Radice, Paolo, Ring, Susan, Rivadeneira, Fernando, Robino, Antonietta, Rose, Lynda M, Rudolph, Anja, Salomaa, Veikko, Sanna, Serena, Schlessinger, David, Schmidt, Marjanka K, Southey, Mellissa C, Sovio, Ulla, Stampfer, Meir J, Stöckl, Dori, Storniolo, Anna M, Timpson, Nicholas J, Tyrer, Jonathan, Visser, Jenny A, Vollenweider, Peter, Völzke, Henry, Waeber, Gerard, Waldenberger, Melanie, Wallaschofski, Henri, Wang, Qin, Willemsen, Gonneke, Winqvist, Robert, Wolffenbuttel, Bruce H. R, Wright, Margaret J, Boomsma, Dorret I, Econs, Michael J, Khaw, Kay Tee, Loos, Ruth J. F, Mccarthy, Mark I, Montgomery, Grant W, Rice, John P, Streeten, Elizabeth A, Thorsteinsdottir, Unnur, van Duijn, Cornelia M, Alizadeh, Behrooz Z, Bergmann, Sven, Boerwinkle, Eric, Boyd, Heather A, Crisponi, Laura, Gasparini, Paolo, Gieger, Christian, Harris, Tamara B, Ingelsson, Erik, Järvelin, Marjo Riitta, Kraft, Peter, Lawlor, Debbie, Metspalu, Andre, Pennell, Craig E, Ridker, Paul M, Snieder, Harold, Sørensen, Thorkild I. A, Spector, Tim D, Strachan, David P, Uitterlinden, André G, Wareham, Nicholas J, Widen, Elisabeth, Zygmunt, Marek, Murray, Anna, Easton, Douglas F, Stefansson, Kari, Murabito, Joanne M, Ong, Ken K., Panico, Salvatore, Perry, John R. B., Elks, Cathy E., Thompson, Deborah J., Chasman, Daniel I., Ang, Wei Q., Cousminer, Diana L., Johnson, Andrew D., Lunetta, Kathryn L., Nolte, Ilja M., Smith, Albert V., Wagner, Erin K., Bierut, Laura J., Byrne, Enda M., Koller, Daniel L., Pers, Tune H., Yerges Armstrong, Laura M., Zhao, Jing Hua, Andrulis, Irene L., Beckmann, Matthias W., Bojesen, Stig E., Bolla, Manjeet K., Buring, Julie E., Couch, Fergus J., Coviello, Andrea D., D'Adamo, ADAMO PIO, Smith, George Davey, Demerath, Ellen W., Dieffenbach, Aida K., Dunning, Alison M., Eriksson, Johan G., Fasching, Peter A., Garcia, Melissa E., De Geus, Eco E. J., Giles, Graham G., Gudbjartsson, Daniel F., Hartman, Catharina A., Heath, Andrew C., Hooning, Maartje J., Hopper, John L., Hu, Frank B., Hunter, David J., Kiel, Douglas P., Knight, Julia A., Magnusson, Patrik K., Martin, Nicholas G., Mcardle, Patrick F., Mcardle, Wendy L., Milne, Roger L., Nohr, Ellen A., Oldehinkel, Albertine J., Oostra, Ben A., Pedersen, Nancy L., Pharoah, Paul D. P., Postma, Dirkje S., Rose, Lynda M., Schmidt, Marjanka K., Southey, Mellissa C., Stampfer, Meir J., Storniolo, Anna M., Timpson, Nicholas J., Visser, Jenny A., Wolffenbuttel, Bruce H. R., Wright, Margaret J., Boomsma, Dorret I., Econs, Michael J., Loos, Ruth J. F., Mccarthy, Mark I., Montgomery, Grant W., Rice, John P., Streeten, Elizabeth A., Van Duijn, Cornelia M., Alizadeh, Behrooz Z., Boyd, Heather A., Harris, Tamara B., Pennell, Craig E., Ridker, Paul M., Sørensen, Thorkild I. A., Spector, Tim D., Strachan, David P., Uitterlinden, André G., Wareham, Nicholas J., Easton, Douglas F., and Murabito, Joanne M.

Subjects
Netherlands Twin Register (NTR), Male, Parents, CENTRAL PRECOCIOUS PUBERTY, Genome-wide association study, Disease, VARIANTS, DISEASE, Body Mass Index, 0302 clinical medicine, Adolescent, Age Factors, Alleles, Breast Neoplasms/genetics, Cardiovascular Diseases/genetics, Child, Diabetes Mellitus, Type 2/genetics, Europe/ethnology, Female, Genetic Loci/genetics, Genome-Wide Association Study, Genomic Imprinting/genetics, Humans, Hypothalamo-Hypophyseal System/physiology, Intercellular Signaling Peptides and Proteins/genetics, Membrane Proteins/genetics, Menarche/genetics, Obesity/genetics, Ovary/physiology, Polymorphism, Single Nucleotide/genetics, Potassium Channels, Tandem Pore Domain/genetics, Proteins/genetics, Quantitative Trait Loci/genetics, Receptors, GABA-B/metabolism, Receptors, Retinoic Acid/metabolism, Ribonucleoproteins/genetics, Intercellular Signaling Peptides and Protein, Age Factor, Tandem Pore Domain, GENE-EXPRESSION, 0303 health sciences, BREAST-CANCER RISK, 3. Good health, Ribonucleoproteins, Cardiovascular Diseases, Menarche, Intercellular Signaling Peptides and Proteins, Science & Technology - Other Topics, GENICA Network, Breast Neoplasm, Type 2, Human, Hypothalamo-Hypophyseal System, Quantitative Trait Loci, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, REVEALS, Diabetes Mellitus, Polymorphism, METAANALYSIS, Science & Technology, ta1184, Calcium-Binding Proteins, Proteins, HUMAN PREFRONTAL CORTEX, ta3121, ta3123, Diabetes Mellitus, Type 2, Genetic Loci, CELLS, 030217 neurology & neurosurgery, LifeLines Cohort Study, Potassium Channels, Receptors, Retinoic Acid, Retinoic Acid, Australian Ovarian Cancer Study, Polymorphism (computer science), Cardiovascular Disease, Receptors, WIDE ASSOCIATION, Membrane Protein, Allele, 2. Zero hunger, Genetics, Multidisciplinary, Single Nucleotide, Europe, Multidisciplinary Sciences, kConFab, Breast Neoplasms, Genomic Imprinting, Membrane Proteins, Obesity, Ovary, Polymorphism, Single Nucleotide, Potassium Channels, Tandem Pore Domain, Receptors, GABA-B, General Science & Technology, Ubiquitin-Protein Ligases, Quantitative trait locus, Biology, Healthcare improvement science Radboud Institute for Health Sciences [Radboudumc 18], Early Growth Genetics (EGG) Consortium, 030304 developmental biology, Protein, GABA-B, Ribonucleoprotein, InterAct Consortium, Genetic architecture, Parent, Genomic imprinting
Abstract

Contains fulltext : 136472.pdf (Publisher’s version ) (Closed access) Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 x 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and gamma-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition.

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111. Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity

Author

Dragana Vuckovic, Mariaelisa Graff, M. Arfan Ikram, Marit E. Jørgensen, Lia E. Bang, Gerome Breen, Torben Jørgensen, Matthias Blüher, Ivan Brandslund, Hester M. den Ruijter, Ian Ford, Timo A. Lakka, Jennifer Wessel, J. Wouter Jukema, Adam S. Butterworth, Iris M. Heid, Xiuqing Guo, Shuai Wang, Paul L. Auer, Tamuno Alfred, Katja K.H. Aben, Inês Barroso, Gail Davies, Helen Griffiths, Heather M. Highland, Myriam Fornage, Claudia Langenberg, Daniel R. Witte, Ilaria Gandin, Kent D. Taylor, Patrick T. Ellinor, Matti Uusitupa, Laura M. Yerges-Armstrong, Fotios Drenos, Lars Wallentin, Joanna M. M. Howson, Jaakko Tuomilehto, Andrew D. Morris, Lawrence F. Bielak, Mengmeng Du, Andrew J. Lotery, Ailith Pirie, Francis S. Collins, Eva Rabing Brix Petersen, Carolina Medina-Gomez, Manuel A. Rivas, Maria Karaleftheri, Jan-Håkan Jansson, Peter Kovacs, Jaspal S. Kooner, Markku Laakso, Fredrik Karpe, Markus Perola, Anubha Mahajan, Heather M. Stringham, Rohit Varma, Alex W. Hewitt, Chris J. Packard, Andrew C. Heath, Claudia Schurmann, Nele Friedrich, David Lamparter, Vanisha Mistry, Renée de Mutsert, Unnur Thorsteinsdottir, Naveed Sattar, Jennifer E. Huffman, Dale R. Nyholt, Johanna Kuusisto, Angela L. Mazul, Hanieh Yaghootkar, George Dedoussis, Yadav Sapkota, Elizabeth K. Speliotes, Amanda J. Cox, Jane Gibson, Christian Theil Have, Penny Gordon-Larsen, Alisa K. Manning, Jaakko Kaprio, Sita H. Vermeulen, Stella Trompet, Yucheng Jia, Dennis O. Mook-Kanamori, Torben Hansen, Kathleen Stirrups, Jean Ferrières, Douglas F. Easton, Ruth J. F. Loos, Gerard Pasterkamp, John M. Starr, Tellervo Korhonen, Betina H. Thuesen, Olov Rolandsson, Veikko Salomaa, Eric B. Larson, Thomas F. Vogt, John Danesh, Honghuang Lin, Gaëlle Marenne, Timothy M. Frayling, Anette Varbo, Daniel I. Chasman, Aliki-Eleni Farmaki, Lorraine Southam, Martina Müller-Nurasyid, Katharine R. Owen, Paul Mitchell, Ching-Ti Liu, Massimiliano Cocca, Anette P. Gjesing, Charles Kooperberg, Rebecca S. Fine, Wei Gan, Amy J. Swift, Gerard Tromp, Krina T. Zondervan, Henrik Vestergaard, Katherine S. Ruth, Angela D'Eustacchio, Uwe Völker, Beverley Balkau, Hayato Tada, Ingrid B. Borecki, Xueling Sim, Gudmar Thorleifsson, Wei Zhou, Yiqin Wang, Eleftheria Zeggini, Cora E. Lewis, Michael Boehnke, Evangelos Evangelou, Gabriel Cuellar-Partida, Sven Bergmann, Tinca J. C. Polderman, Philippe Amouyel, Roberta McKean-Cowdin, Ellen W. Demerath, Marco Brumat, Kjell Nikus, Anneke I den Hollander, Stefan Gustafsson, Allan Linneberg, Peter T. Campbell, Weihua Zhang, Leslie A. Lange, Gina M. Peloso, Jonathan P. Bradfield, Cornelia M. van Duijn, Xiaowei Zhan, Marie-Pierre Dubé, Liang He, André G. Uitterlinden, Anne Tybjærg-Hansen, Yingchang Lu, Wei Zhao, Liang Sun, Yii-Der Ida Chen, Paul I. W. de Bakker, Børge G. Nordestgaard, Karina Meidtner, Carsten A. Böger, Lynne E. Wagenknecht, Eric Kim, Pang Yao, Olli T. Raitakari, Nanette R. Lee, René S. Kahn, Lili Milani, Tessel E. Galesloot, Jussi Hernesniemi, Valgerdur Steinthorsdottir, Jie Yao, Eulalia Catamo, Kerrin S. Small, Sara M. Willems, Marcelo P. Segura-Lepe, Cecilia M. Lindgren, Asif Rasheed, Gonçalo R. Abecasis, Adam E. Locke, Konstantin Strauch, Albert V. Smith, Anke R. Hammerschlag, Frida Renström, Zoltán Kutalik, Giovanni Veronesi, Paul M. Ridker, David J. Carey, Yao Hu, Jaana Lindström, John Andrew Pospisilik, Mike A. Nalls, Erik Ingelsson, Colin N. A. Palmer, Mary F. Feitosa, John R. B. Perry, Anne E. Justice, Ele Ferrannini, Shuang Feng, Helen R. Warren, David J. Roberts, Igor Rudan, Jeffrey R. O'Connel, Alison Pattie, Christopher P. Nelson, Lars Lind, Feijie Wang, Tamara B. Harris, Keng-Hung Lin, Jerome I. Rotter, Matthew A. Allison, Robin Young, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Stefan Johansson, Alexander P. Reiner, Jing Hua Zhao, Poorva Mudgal, Tim D. Spector, Paul W. Franks, Loes M. Olde Loohuis, Harvey D. White, Pirjo Komulainen, Michelle L. O'Donoghue, Todd L. Edwards, Ozren Polasek, Andrew R. Wood, Dermot F. Reilly, Myriam Rheinberger, Cramer Christensen, G. Kees Hovingh, Hidetoshi Kitajima, Kristin L. Young, Audrey Y. Chu, Megan L. Grove, Suthesh Sivapalaratnam, Lisa Bastarache, Martin den Heijer, Oddgeir L. Holmen, Vilmundur Gudnason, Sameer E. Al-Harthi, Dewan S. Alam, Robert E. Schoen, Jin Li, Sascha Fauser, Janie Corley, Paolo Gasparini, Niels Grarup, Guillaume Lettre, Thomas N. Person, Mark I. McCarthy, Joel N. Hirschhorn, Ying Wu, Pia R. Kamstrup, Nilesh J. Samani, Panos Deloukas, Ethan M. Lange, Helena Kuivaniemi, Mika Kähönen, Michiel L. Bots, Annette Peters, Peggy L. Peissig, Wayne Huey-Herng Sheu, Steven A. Lubitz, Stefania Cappellani, Mauno Vanhala, Andrew P. Morris, Struan F.A. Grant, Mark Walker, Trevor A. Mori, Jian'an Luan, Matthias B. Schulze, Josh C. Denny, Sarah E. Medland, Sander W. van der Laan, Maggie C.Y. Ng, Eric Boerwinkle, Tibor V. Varga, Øyvind Helgeland, Anke Tönjes, Jessica van Setten, James P. Cook, Patricia B. Munroe, Heiner Boeing, Robert A. Scott, Karen L. Mohlke, Leena Moilanen, Ayush Giri, Andrew J. Slater, Andrew T. Hattersley, Mark J. Caulfield, Tõnu Esko, Mark C. H. Groot, Nancy L. Heard-Costa, Narisu Narisu, Danish Saleheen, Valérie Turcot, Lambertus A. Kiemeney, Nicholas G. D. Masca, Ruifang Li-Gao, Jean-Claude Tardif, Xu Lin, Kathleen Mullan Harris, Antonietta Robino, Alison M. Dunning, Jonathan Tyrer, Audrey E. Hendricks, Linda Broer, Patricia A. Peyser, Jessica D. Faul, Jose C. Florez, Anne U. Jackson, Eirini Marouli, Jette Bork-Jensen, John C. Chambers, Jordi Corominas Galbany, Ruth Frikke-Schmidt, David S. Crosslin, Bratati Kahali, Stavroula Kanoni, Gorm B. Jensen, Nicholas J. Wareham, Paul Elliott, Tune H. Pers, James A. Perry, Tugce Karaderi, Matt J. Neville, Marianne Benn, Svati H. Shah, Mathias Gorski, Michael Stumvoll, David Ellinghaus, Amber A. Burt, Kari E. North, Jeffrey Haessler, Rajiv Chowdhury, Folkert W. Asselbergs, Marie Moitry, Aniruddh P. Patel, Pamela J. Schreiner, Frank Kee, Donald W. Bowden, Sune F. Nielsen, Oluf Pedersen, John D. Rioux, Rainer Rauramaa, Satu Männistö, Deborah J. Thompson, Cristen J. Willer, Andre Franke, Kari Kuulasmaa, Nienke van Leeuwen, Carmel Moore, Sharon L.R. Kardia, Neil R. Robertson, Sekar Kathiresan, Erin B. Ware, Dawn M. Waterworth, James G. Wilson, Sandosh Padmanabhan, Emmanouil Tsafantakis, Hakon Hakonarson, Dajiang J. Liu, Digna R. Velez Edwards, Artitaya Lophatananon, Craig E. Pennell, Gail P. Jarvik, Adelheid Lempradl, Anu Loukola, Joe Dennis, Hans-Jörgen Grabe, Oscar H. Franco, Yongmei Liu, I. Sadaf Farooqi, Hannu Puolijoki, Huaixing Li, Caroline Hayward, Rudolf Uher, Veronique Vitart, Murray H. Brilliant, Kari Stefansson, Alexander Teumer, Nicholette D. Palmer, Vilmantas Giedraitis, Roel A. Ophoff, Sailaja Vedantam, Emanuele Di Angelantonio, Ken S. Lo, Grant W. Montgomery, Paul L. Huang, Praveen Surendran, Terho Lehtimäki, Katherine E. Tansey, Li-An Lin, Pål R. Njølstad, Thomas W. Winkler, Ian J. Deary, Erwin P. Bottinger, Carol A. Wang, Biological Psychology, Complex Trait Genetics, and Amsterdam Neuroscience - Complex Trait Genetics

Subjects
0301 basic medicine, 2. Zero hunger, 0303 health sciences, ComputerSystemsOrganization_COMPUTERSYSTEMIMPLEMENTATION, Published Erratum, Computational biology, Biology, medicine.disease, Obesity, Genealogy, 3. Good health, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, ddc:570, Genetics, medicine, ComputingMethodologies_DOCUMENTANDTEXTPROCESSING, Biological sciences, Body mass index, 030217 neurology & neurosurgery, 030304 developmental biology
Abstract

In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

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