Genome-Wide Association Analysis of High-Density Lipoprotein Cholesterol in the Population-Based KORA Study Sheds New Light on Intergenic Regions

Genome-Wide Association Analysis of High-Density Lipoprotein Cholesterol in the Population-Based KORA Study Sheds New Light on Intergenic Regions Iris M. Heid, PhD ; Eva Boes, MSc ; Martina Müller, MSc ; Barbara Kollerits, MSc ; Claudia Lamina, MSc ; Stefan Coassin, MSc ; Christian Gieger, PhD ; Angela Döring, MD ; Norman Klopp, PhD ; Ruth Frikke-Schmidt, MD, PhD ; Anne Tybjærg-Hansen, MD ; Anita Brandstätter, PhD ; Andreas Luchner, MD ; Thomas Meitinger, MD ; H.-Erich Wichmann, MD, PhD and Florian Kronenberg, MD From the Institute of Epidemiology (I.M.H., M.M., C.L., C.G., A.D., N.K., H.-E.W.) and Institute of Human Genetics (T.M.), Helmholtz Center Munich, German Research Center for Environmental Health, Neuherberg, Germany; Institute of Information Management, Biometry and Epidemiology (I.M.H., M.M., N.K., H.-E.W.), Ludwig Maximilians University of Munich, Munich, Germany; Division of Genetic Epidemiology (E.B., B.K., S.C., A.B., F.K.), Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Innsbruck, Austria; Department of Clinical Biochemistry (R.F.-S., A.T.-H.), Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; The Copenhagen City Heart Study (A.T.-H.), Bispebjerg Hospital, Copenhagen University Hospital, Copenhagen, Denmark; Internal Medicine II (A.L.), University of Regensburg, Regensburg, Germany; and Institute of Human Genetics (T.M.), Technical University Munich, Munich, Germany. Correspondence to Florian Kronenberg, MD, Division of Genetic Epidemiology, Department of Medical Genetics, Molecular and Clinical Pharmacology, Innsbruck Medical University, Schöpfstraße 41, A-6020 Innsbruck, Austria. E-mail Florian.Kronenberg{at}i-med.ac.at Received February 29, 2008; accepted June 13, 2008. Background— High-density lipoprotein cholesterol (HDLC) is a strong risk factor for atherosclerosis and is assumed to be under considerable genetic control. We aimed to identify gene regions that influence HDLC levels by a genome-wide association analysis in the population-based KORA (Cooperative Health Research in the Region of Augsburg) study. Methods and Results— In KORA S3/F3 (n=1643), we analyzed 377 865 quality-checked single-nucleotide polymorphisms (SNPs; 500K, Affymetrix, Santa Clara, Calif), complemented by the publicly available genome-wide association results from the Diabetes Genetics Initiative (n=2631) and by replication data from KORA S4 (n=4037) and the Copenhagen City Heart Study (n=9