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Childhood obesity is increasing worldwide at rates of epidemic proportion (1, 2). Previously a public health concern of only the modern, industrialized world, this problem now increasingly affects children and adolescents of poor, developing countries. This new and somewhat baffling phenomenon urgently begs the question: How is it that impoverished children around the world become obese? Recent studies suggest that rapid globalization and urbanization account for significant shifts in dietary patterns and physical activity levels that tend to increase risks for obesity in children. Industrialized agro-food systems established by global corporations have made cheap calorie-dense foods, fats, and oils widely available across the world and have caused what researchers call a "nutrition transition". This new global diet has led to increases in fat consumption worldwide (2, 5). Rapidly increasing urbanization has resulted in greater dependence on mechanized transportation and the loss of safe, open spaces for physical activity (2, 5). The combination of increasingly sedentary lifestyles and a lipid-rich diet is documented both in children of poor countries, as well as among impoverished children of the US and other industrialized nations. The global nature of this epidemiological trend indicates that global interventions will be necessary to adequately address the social, economic, and political forces that impact access to healthy food, and voluntary participation in physical activity and consequently lead to increasing rates of childhood obesity worldwide.

Discusses Ann Petry's short story, "Like a Winding Sheet" (1946), in the context of black feminist literary theory, exploring the possibility of developing a reading strategy that does not replicate the effacement of black women's subjectivities. Petry's story is read as a delineation of the impossible position of black female flesh in US cultural discourse; the black female subject is erased & simultaneously constructed as ungendered flesh. It is suggested that black feminist literary criticism has failed to create a vocabulary that speaks to the specificity & diversity of African American women's experiences in the US. Instead, it has worked against the available cultural categories to reduce the complexity of black female lives to the status of incoherent differences. Merely being heard will not solve the problem of black female unrepresentability; a theorization of the discursive conditions that allow complex subjects to be rendered as singular social agents is advocated. D. M. Smith

Frontmatter -- CONTENTS -- PREFACE -- Introduction -- PART ONE. Identity Theories and New Frameworks -- 1. Nontraditional, Nonconforming, and Transgressive Gender Expression and Relationship Modalities in Black Communities / Phillips, Layli / Stewart, Marla R. -- 2. Creation Out of Bounds / Cunningham, E. Christi -- 3. On the Fear of Small Numbers / Page, Enoch H. / Richardson, Matt U. -- 4. Blackness, Sexuality, and Transnational Desire / Allen, Jafari S. -- PART TWO. Descriptions, Depictions, and Responses -- 5. Pathologizing Black Sexuality / Mcgruder, Kevin -- 6. Dangerous Profiling / Tapia, Ruby / Mccune, Jeffrey / Brody, Jennifer Devere -- 7. Revisiting Black Sexualities in Families Problems, Puzzles, and Prospects / Childs, Erica Chito / Laudone, Stephanie / Tavernier, Latoya -- 10. Black Sexual Citizenship / Cahill, Sean -- 11. Racialized Justice Spreads HIV/AIDS among Blacks / Lemelle, Anthony J. -- 12. Black and Latino Same-Sex Couple Households and the Racial Dynamics of Antigay Activism / Cahill, Sean -- PART FOUR. Negotiating Systemic and Personal Stresses -- 13. Blacks and Racial Appraisals / Mcguffey, C. Shawn -- 14. When Secrets Hurt / Peterson, Robert -- 15. Black Female Sex Workers / Tatum, Stephanie L. -- 16. Yes, Jesus Loves Me / Rawls, Tonyia M. -- PART FIVE. The Life Course -- 17. Black Mother-Daughter Narratives about Sexuality / Barnes, Sandra L. / Bynum, Mia Smith -- 18. Black Youth Sexuality / Hunter, Marcus Anthony / Guerrero, Marissa / Cohen, Cathy J. -- 19. "I'll Be Forever Mackin' " / Gray, Jonathan W. -- 20. Black Senior Women and Sexuality / Dickerson, Bette J. / Rousseau, Nicole -- Epilogue -- NOTES ON CONTRIBUTORS -- INDEX

Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are associated with thrombosis risk and increased gastrointestinal bleeding risk, respectively. Our WGS findings add to previously identified GWAS loci, provide insights regarding the mechanism(s) by which genetics may influence cardiovascular disease risk, and underscore the importance of rare variant and regulatory approaches to identifying loci contributing to complex phenotypes. © 2021, This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply. ; National Institutes of Health ; https://doi.org/10.1038/s41467-021-23470-9

This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. Acknowledgements: We especially thank all volunteers who participated in our study. This study made use of data generated by the 'Genome of the Netherlands' project, which is funded by the Netherlands Organization for Scientific Research (grant no. 184021007). The data were made available as a Rainbow Project of BBMRI-NL. Samples were contributed by LifeLines (http://lifelines.nl/lifelines-research/general), the Leiden Longevity Study (http://www.healthy-ageing.nl; http://www.langleven.net), the Netherlands Twin Registry (NTR: http://www.tweelingenregister.org), the Rotterdam studies (http://www.erasmus-epidemiology.nl/rotterdamstudy) and the Genetic Research in Isolated Populations programme (http://www.epib.nl/research/geneticepi/research.html#gip). The sequencing was carried out in collaboration with the Beijing Institute for Genomics (BGI). Cardiovascular Health Study: This CHS research was supported by NHLBI contracts HHSN268201200036C, HHSN268200800007C, HHSN268200960009C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants HL080295, HL087652, HL105756 and HL103612 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through AG023629 from the National Institute on Aging (NIA). A full list of CHS investigators and institutions can be found at http://www.chs-nhlbi.org/pi.htm. The CROATIA cohorts would like to acknowledge the invaluable contributions of the recruitment teams in Vis, Korcula and Split (including those from the Institute of Anthropological Research in Zagreb and the Croatian Centre for Global Health at the University of Split), the administrative teams in Croatia and Edinburgh and the people of Vis, Korcula and Split. SNP genotyping was performed at the Wellcome Trust Clinical Research Facility in Edinburgh for CROATIA-Vis, by Helmholtz Zentrum München, GmbH, Neuherberg, Germany for CROATIA-Korcula and by AROS Applied Biotechnology, Aarhus, Denmark for CROATIA-Split. They would also like to thank Jared O'Connell for performing the pre-phasing for all cohorts before imputation. The ERF study as a part of EuroSPAN (European Special Populations Research Network) was supported by European Commission FP-6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007-2013)/grant agreement HEALTH-F4-2007-201413 by the European Commission under the programme 'Quality of Life and Management of the Living Resources' of 5th Framework Programme (no. QLG2-CT-2002-01254). High-throughput analysis of the ERF data was supported by joint grant from the Netherlands Organisation for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). This research was financially supported by BBMRI-NL, a Research Infrastructure financed by the Dutch government (NWO 184.021.007). Statistical analyses for the ERF study were carried out on the Genetic Cluster Computer (http://www.geneticcluster.org), which is financially supported by the Netherlands Scientific Organization (NWO 480-05-003 PI: Posthuma) along with a supplement from the Dutch Brain Foundation and the VU University Amsterdam. We are grateful to all study participants and their relatives, general practitioners and neurologists for their contributions and to P. Veraart for her help in genealogy, J. Vergeer for the supervision of the laboratory work and P. Snijders for his help in data collection. The FamHS is funded by a NHLBI grant 5R01HL08770003, and NIDDK grants 5R01DK06833603 and 5R01DK07568102. The Framingham Heart Study SHARe Project for GWAS scan was supported by the NHLBI Framingham Heart Study (Contract No. N01-HC-25195) and its contract with Affymetrix Inc for genotyping services (Contract No. N02-HL-6-4278). DNA isolation and biochemistry were partly supported by NHLBI HL-54776. A portion of this research utilized the Linux Cluster for Genetic Analysis (LinGA-II) funded by the Robert Dawson Evans Endowment of the Department of Medicine at the Boston University School of Medicine and Boston Medical Center. We are grateful to Han Chen for conducting the 1000G imputation. The Family Heart Study was supported by the by grants R01-HL-087700 and R01-HL-088215 from the National Heart, Lung, and Blood Institute (NHLBI). We would like to acknowledge the invaluable contributions of the families who took part in the Generation Scotland: Scottish Family Health Study, the general practitioners and Scottish School of Primary Care for their help in recruiting them, and the whole Generation Scotland team, which includes academic researchers, IT staff, laboratory technicians, statisticians and research managers. SNP genotyping was performed at the Wellcome Trust Clinical Research Facility in Edinburgh. GS:SFHS is funded by the Scottish Executive Health Department, Chief Scientist Office, grant number CZD/16/6. SNP genotyping was funded by the Medical Research Council, United Kingdom. We wish to acknowledge the services of the LifeLines Cohort Study, the contributing research centres delivering data to LifeLines and all the study participants. MESA Whites and the MESA SHARe project are conducted and supported by contracts N01-HC-95159 through N01-HC-95169 and RR-024156 from the NHLBI. Funding for MESA SHARe genotyping was provided by NHLBI Contract N02.HL.6.4278. MESA Family is conducted and supported in collaboration with MESA investigators; support is provided by grants and contracts R01HL071051, R01HL071205, R01HL071250, R01HL071251, R01HL071252, R01HL071258 and R01HL071259. We thank the participants of the MESA study, the Coordinating Center, MESA investigators and study staff for their valuable contributions. A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org. Netherland Twin Register (NTR) and Netherlands Study of Depression and Anxiety (NESDA): Funding was obtained from the Netherlands Organization for Scientific Research (NWO) and MagW/ZonMW grants Middelgroot-911-09-032, Spinozapremie 56-464-14192, Geestkracht programme of the Netherlands Organization for Health Research and Development (Zon-MW, grant number 10-000-1002), Center for Medical Systems Biology (CSMB, NWO Genomics), NBIC/BioAssist/RK(2008.024), Biobanking and Biomolecular Resources Research Infrastructure (BBMRI-NL, 184.021.007), VU University's Institute for Health and Care Research (EMGO+) and Neuroscience Campus Amsterdam (NCA); the European Science Foundation (ESF, EU/QLRT-2001-01254), the European Community's Seventh Framework Program (FP7/2007-2013), ENGAGE (HEALTH-F4-2007-201413); the European Science Council (ERC Advanced, 230374); and the European Research Council (ERC-284167). Part of the genotyping and analyses were funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health, Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1, MH081802, Grand Opportunity grants 1RC2 MH089951 and 1RC2 MH089995). PREVEND genetics is supported by the Dutch Kidney Foundation (Grant E033), the EU project grant GENECURE (FP-6 LSHM CT 2006 037697), the National Institutes of Health (grant 2R01LM010098), The Netherlands Organisation for Health Research and Development (NWO-Groot grant 175.010.2007.006, NWO VENI grant 916.761.70, ZonMw grant 90.700.441) and the Dutch Inter University Cardiology Institute Netherlands (ICIN). The PROSPER study was supported by an investigator-initiated grant obtained from Bristol-Myers Squibb. J.W.J is an Established Clinical Investigator of the Netherlands Heart Foundation (grant 2001 D 032). Genotyping was supported by the seventh framework programme of the European commission (grant 223004) and by the Netherlands Genomics Initiative (Netherlands Consortium for Healthy Aging grant 050-060-810). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII) and the Municipality of Rotterdam. We are grateful to the study participants, the staff from the Rotterdam Study and the participating general practitioners and pharmacists. The generation and management of GWAS genotype data for the Rotterdam Study is supported by the Netherlands Organisation of Scientific Research NWO Investments (nr. 175.010.2005.011, 911-03-012). This study is funded by the Research Institute for Diseases in the Elderly (014-93-015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organisation for Scientific Research (NWO) project no. 050-060-810. We thank Pascal Arp, Mila Jhamai, Marijn Verkerk, Lizbeth Herrera and Marjolein Peters for their help in creating the GWAS database. ; Peer reviewed ; Publisher PDF

Publisher's version (útgefin grein). ; Background: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear. Results: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction. Conclusions: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes. ; Funding This work was funded by a grant to YJ from the British Heart Foundation (PG/12/38/29615). AGES: This study has been funded by NIH contracts N01-AG-1-2100 and 271201200022C, the NIA Intramural Research Program, Hjartavernd (the Icelandic Heart Association), and the Althingi (the Icelandic Parliament). The study is approved by the Icelandic National Bioethics Committee, VSN: 00–063. The researchers are indebted to the participants for their willingness to participate in the study. ARIC: The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. The authors thank the staff and participants of the ARIC study for their important contributions. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Funding support for "Building on GWAS for NHLBI-diseases: the U.S. CHARGE consortium" was provided by the NIH through the American Recovery and Reinvestment Act of 2009 (ARRA) (5RC2HL102419). BRIGHT: The Exome Chip genotyping was funded by Wellcome Trust Strategic Awards (083948 and 085475). This work was also supported by the Medical Research Council of Great Britain (Grant no. G9521010D); and by the British Heart Foundation (Grant no. PG/02/128). AFD was supported by the British Heart Foundation (Grant nos. RG/07/005/23633 and SP/08/005/25115); and by the European Union Ingenious HyperCare Consortium: Integrated Genomics, Clinical Research, and Care in Hypertension (grant no. LSHM-C7–2006-037093). The BRIGHT study is extremely grateful to all the patients who participated in the study and the BRIGHT nursing team. We would also like to thank the Barts Genome Centre staff for their assistance with this project. CHS: This Cardiovascular Health Study (CHS) research was supported by NHLBI contracts HHSN268201800001C, HHSN268201200036C, HHSN268200800007C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, N01HC85086; and NHLBI grants R01HL068986, U01HL080295, R01HL087652, R01HL105756, R01HL103612, R01HL120393, and U01HL130114 with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided through R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org. The provision of genotyping data was supported in part by the National Center for Advancing Translational Sciences, CTSI grant UL1TR001881, and the National Institute of Diabetes and Digestive and Kidney Disease Diabetes Research Center (DRC) grant DK063491 to the Southern California Diabetes Endocrinology Research Center. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. ERF: The ERF study as a part of EUROSPAN (European Special Populations Research Network) was supported by European Commission FP6 STRP grant number 018947 (LSHG-CT-2006-01947) and also received funding from the European Community's Seventh Framework Programme (FP7/2007–2013)/grant agreement HEALTH-F4–2007-201413 by the European Commission under the programme "Quality of Life and Management of the Living Resources" of 5th Framework Programme (no. QLG2-CT-2002-01254). The ERF study was further supported by ENGAGE consortium and CMSB. High-throughput analysis of the ERF data was supported by joint grant from Netherlands Organization for Scientific Research and the Russian Foundation for Basic Research (NWO-RFBR 047.017.043). We are grateful to all study participants and their relatives, general practitioners, and neurologists for their contributions to the ERF study and to P Veraart for her help in genealogy, J Vergeer for the supervision of the laboratory work, and P Snijders for his help in data collection. FHS: The Framingham Heart Study (FHS) research reported in this article was supported by a grant from the National Heart, Lung, and Blood Institute (NHLBI), HL120393. Generation Scotland: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Genotyping of the Generation Scotland and Scottish Family Health Study samples was carried out by the Genetics Core Laboratory at the Clinical Research Facility, Edinburgh, Scotland and was funded by the UK's Medical Research Council. GOCHA: The Genetics of Cerebral Hemorrhage with Anticoagulation was carried out as a collaborative study supported by grants R01NS073344, R01NS059727, and 5K23NS059774 from the NIH–National Institute of Neurological Disorders and Stroke (NIH-NINDS). GRAPHIC: The GRAPHIC Study was funded by the British Heart Foundation (BHF/RG/2000004). NJS and CPN are supported by the British Heart Foundation and is a NIHR Senior Investigator. This work falls under the portfolio of research supported by the NIHR Leicester Cardiovascular Biomedical Research. INGI-FVG: This study has been funded by Regione FVG (L.26.2008). INTER99: The Inter99 was initiated by Torben Jørgensen (PI), Knut Borch-Johnsen (co-PI), Hans Ibsen and Troels F. Thomsen. The steering committee comprises the former two and Charlotta Pisinger. The study was financially supported by research grants from the Danish Research Council, the Danish Centre for Health Technology Assessment, Novo Nordisk Inc., Research Foundation of Copenhagen County, Ministry of Internal Affairs and Health, the Danish Heart Foundation, the Danish Pharmaceutical Association, the Augustinus Foundation, the Ib Henriksen Foundation, the Becket Foundation, and the Danish Diabetes Association. The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent Research Center at the University of Copenhagen partially funded by an unrestricted donation from the Novo Nordisk Foundation (www.metabol.ku.dk). JHS: We thank the Jackson Heart Study (JHS) participants and staff for their contributions to this work. The JHS is supported by contracts HHSN268201300046C, HHSN268201300047C, HHSN268201300048C, HHSN268201300049C, HHSN268201300050C from the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. Dr. Wilson is supported by U54GM115428 from the National Institute of General Medical Sciences. KORA: The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC-Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. Korcula: This work was funded by the Medical Research Council UK, The Croatian Ministry of Science, Education and Sports (grant 216–1080315-0302), the Croatian Science Foundation (grant 8875), the Centre of Excellence in Personalized health care, and the Centre of Competencies for Integrative Treatment, Prevention and Rehabilitation using TMS. LifeLines: The LifeLines Cohort Study and generation and management of GWAS genotype data for the LifeLines Cohort Study are supported by The Netherlands Organization of Scientific Research NWO (grant 175.010.2007.006), the Economic Structure Enhancing Fund (FES) of the Dutch government, the Ministry of Economic Affairs, the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the Northern Netherlands Collaboration of Provinces (SNN), the Province of Groningen, University Medical Center Groningen, the University of Groningen, Dutch Kidney Foundation, and Dutch Diabetes Research Foundation. Niek Verweij is supported by NWO-VENI (016.186.125) and Marie Sklodowska-Curie GF (call: H2020-MSCA-IF-2014, Project ID: 661395). UHP: Folkert W. Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre. Ilonca Vaartjes is supported by a Dutch Heart Foundation grant DHF project "Facts and Figures." MGH-CAMP: Dr. Patrick Ellinor is funded by NIH grants (2R01HL092577, 1R01HL128914, R01HL104156, and K24HL105780) and American Heart Association Established Investigator Award 13EIA14220013 (Ellinor). Dr. Steve Lubitz is funded by NIH grants K23HL114724 and a Doris Duke Charitable Foundation Clinical Scientist Development Award 2014105. NEO: The authors of the NEO study thank all individuals who participated in the Netherlands Epidemiology in Obesity study, all participating general practitioners for inviting eligible participants, and all research nurses for collection of the data. We thank the NEO study group, Pat van Beelen, Petra Noordijk, and Ingeborg de Jonge for the coordination, lab, and data management of the NEO study. We also thank Arie Maan for the analyses of the electrocardiograms. The genotyping in the NEO study was supported by the Centre National de Génotypage (Paris, France), headed by Jean-Francois Deleuze. The NEO study is supported by the participating Departments, the Division and the Board of Directors of the Leiden University Medical Center, and by the Leiden University, Research Profile Area Vascular and Regenerative Medicine. Dennis Mook-Kanamori is supported by Dutch Science Organization (ZonMW-VENI Grant 916.14.023). RS-I: The generation and management of the Illumina Exome Chip v1.0 array data for the Rotterdam Study (RS-I) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The Exome chip array dataset was funded by the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, from the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO)-sponsored Netherlands Consortium for Healthy Aging (NCHA; project nr. 050–060-810); the Netherlands Organization for Scientific Research (NWO; project number 184021007); and by the Rainbow Project (RP10; Netherlands Exome Chip Project) of the Biobanking and Biomolecular Research Infrastructure Netherlands (BBMRI-NL; www.bbmri.nl). We thank Ms. Mila Jhamai, Ms. Sarah Higgins, and Mr. Marijn Verkerk for their help in creating the exome chip database, and Carolina Medina-Gomez, MSc, Lennard Karsten, MSc, and Linda Broer PhD for QC and variant calling. Variants were called using the best practice protocol developed by Grove et al. as part of the CHARGE consortium exome chip central calling effort. The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff from the Rotterdam Study, and the participating general practitioners and pharmacists. The work of Bruno H. Stricker is supported by grants from the Netherlands Organization for Health Research and Development (ZonMw) (Priority Medicines Elderly 113102005 to ME and DoelmatigheidsOnderzoek 80–82500–98-10208 to BHS). The work of Mark Eijgelsheim is supported by grants from the Netherlands Organization for Health Research and Development (ZonMw) (Priority Medicines Elderly 113102005 to ME and DoelmatigheidsOnderzoek 80–82500–98-10208 to BHS). SHIP: SHIP is supported by the BMBF (grants 01ZZ9603, 01ZZ0103, and 01ZZ0403) and the German Research Foundation (Deutsche Forschungsgemeinschaft [DFG]; grant GR 1912/5–1). SHIP and SHIP-TREND are part of the Community Medicine Research net (CMR) of the Ernst-Moritz-Arndt University Greifswald (EMAU) which is funded by the BMBF as well as the Ministry for Education, Science and Culture and the Ministry of Labor, Equal Opportunities, and Social Affairs of the Federal State of Mecklenburg-West Pomerania. The CMR encompasses several research projects that share data from SHIP. The EMAU is a member of the Center of Knowledge Interchange (CKI) program of the Siemens AG. SNP typing of SHIP and SHIP-TREND using the Illumina Infinium HumanExome BeadChip (version v1.0) was supported by the BMBF (grant 03Z1CN22). We thank all SHIP and SHIP-TREND participants and staff members as well as the genotyping staff involved in the generation of the SNP data. TWINSUK: TwinsUK is funded by the Wellcome Trust, Medical Research Council, European Union, the National Institute for Health Research (NIHR)-funded BioResource, Clinical Research Facility and Biomedical Research Centre based at Guy's and St Thomas' NHS Foundation Trust in partnership with King's College London. UKBB: This research has been conducted using the UK Biobank Resource (application 8256 - Understanding genetic influences in the response of the cardiac electrical system to exercise) and is supported by Medical Research Council grant MR/N025083/1. We also wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Unit at Barts and Queen Mary University of London, UK. PD Lambiase acknowledges support from the UCLH Biomedicine NIHR. MO is supported by an IEF 2013 Marie Curie fellowship. JR acknowledges support from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007–2013) under REA grant agreement no. 608765. YFS: The Young Finns Study has been financially supported by the Academy of Finland: grants 286284, 134309 (Eye), 126925, 121584, 124282, 129378 (Salve), 117787 (Gendi), and 41071 (Skidi); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); Juho Vainio Foundation; Paavo Nurmi Foundation; Finnish Foundation for Cardiovascular Research; Finnish Cultural Foundation; Tampere Tuberculosis Foundation; Emil Aaltonen Foundation; Yrjö Jahnsson Foundation; Signe and Ane Gyllenberg Foundation; and Diabetes Research Foundation of Finnish Diabetes Association. The expert technical assistance in the statistical analyses by Irina Lisinen is gratefully acknowledged. Cell culture and biochemistry: Funding was provided by the National Institutes of Health (Program of Excellence in Glycoscience award HL107147 to SSA and F32AR063548 to TJM) and the David and Lindsay Morgenthaler Postdoctoral Fellowship (to TJM) and by the Allen Distinguished Investigator Program, through support made by The Paul G. Allen Frontiers Group and the American Heart Association (to SSA). Mutant mouse model: Adamts6 mutant mice were generated and further propagated and analyzed by funding provided by NIH grants HL098180 and HL132024 (to CWL) and by the Allen Distinguished Investigator Program, through support made by The Paul G. Allen Frontiers Group and the American Heart Association (to SSA). ; Peer Reviewed