MSSE SPECIAL REPORT The human gene map for performance and health-related fitness phenotypes: the 2001 update TUOMO RANKINEN, LOUIS PE ´ RUSSE, RAINER RAURAMAA, MIGUEL A. RIVERA, BERND WOLFARTH, and CLAUDE BOUCHARD Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA; Physical Activity Sciences Laboratory, Laval University, Ste-Foy, Que ´bec, CANADA; Kuopio Research Institute of Exercise Medicine, Department of Physiology, University of Kuopio and Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, FINLAND; Department of Physiology and Department of Physical Medicine, Rehabilitation and Sports Medicine, University of Puerto Rico School of Medicine, San Juan, PUERTO RICO; and Department of Preventive and Rehabilitative Sports Medicine, University of Freiburg, Freiburg, GERMANY ABSTRACT RANKINEN, T., L. PE ´ RUSSE, R. RAURAMAA, M. A. RIVERA, B. WOLFARTH, and C. BOUCHARD. The human gene map for performance and health-related fitness phenotypes: the 2001 update. Med. Sci. Sports Exerc., Vol. 34, No. 8, pp. 1219 –1233, 2002. This review presents the 2001 update of the human gene map for physical performance and health-related phenotypes. It is based on scientific papers published by the end of 2001. Association studies with candidate genes, genome-wide scans with polymorphic markers, and single gene defects causing exercise intolerance to variable degrees are included. The genes and markers with evidence of association or linkage with a performance or fitness phenotype in sedentary or active people, in adaptation to acute exercise or for training-induced changes are positioned on the genetic map of all autosomes and the X chromosome. Negative studies are reviewed, but a gene or locus must be supported by at least one positive study before being inserted on the map. By the end of 2000, there were 29 loci depicted on the map. The 2001 map includes 71 loci on the autosomes and two on the X chromosome. Among these genes or markers, 24 are from prior publications on exercise intolerance and four relate to other pathologies. Finally, 13 sequence variants in mitochondrial DNA have been shown to influence relevant fitness and performance phenotypes. T his paper constitutes the second installment in the series on the human gene map for performance and health-related fitness phenotypes. It covers the peer- reviewed literature published by the end of December 2001. The goal of these reviews is to include all genetic loci and markers shown to be related to fitness or performance in at least one study. Negative studies are briefly reviewed for a balanced presentation of the evidence. However, the non- significant results are generally not incorporated in the sum- mary tables. There are two important differences between the 2001 review as compared with the first installment. First, the results of early case-control studies of Olympic athletes based on common red blood cell antigenic systems and polymorphic red blood cell enzymes, which were reviewed in detail last year, have been dropped from this year’s review. All these studies were essentially negative. The interested reader can consult Table 2 of the first installment of the gene map for a complete summary of these early reports (78). Second, the decision was taken to include exercise intolerance as a performance phenotype. There is a strong body of data indicating that mutations in specific genes are often characterized by a diminished ability to exercise or perform. These cases are typically found for genes encoding enzymes of pathways related to substrate storage or mobilization. They provide excellent examples of single genes having strong negative effects on physical performance. Because these genes were not reviewed last year, we have briefly summarized the evidence accumulated to date in this paper. The physical performance phenotypes for which genetic data are available include cardiorespiratory endurance, elite endurance athlete status, muscle strength, other muscle per- formance traits, and exercise intolerance of variable de- grees. Consistent with the first review, the phenotypes of health-related fitness retained are grouped under the follow- ing categories: hemodynamic traits including exercise heart rate, blood pressure, and heart morphology; anthropometry and body composition; insulin and glucose metabolism; and blood lipid, lipoprotein, and hemostatic factors. Here, we 0195-9131/02/3408-1219/$3.00/0 MEDICINE & SCIENCE IN SPORTS & EXERCISE ® Copyright © 2002 by the American College of Sports Medicine Submitted for publication March 2002. Accepted for publication April 2002. 1219