Abstract To identify genes that influence plasma cho- lesterol, triglyceride, and high-density and low-density lipoproteins concentrations we conducted a genome- wide scan using 354 polymorphic markers spaced at 10-cM intervals in 75 obese but otherwise normal human families. The results of the genome scan using sibling pair analysis of quantitative phenotypes suggested that 1q21–q23 contains a locus that influences plasma cho- lesterol concentration. Chromosome 12 gave evidence of linkage to plasma triglyceride concentration (D12SPAH) and chromosomes 3, 6, 7, 10, 11, 17, and 20 yielded ad- ditional evidence of linkage for lipid phenotypes at lower levels of statistical significance. Allele sharing for mark- ers near prominent candidate genes was either very weakly related or unrelated to sibling similarity for lipid concentrations. Together these results suggest that genes with important roles in regulating normal cholesterol and triglyceride concentrations do not coincide with the loca- tion of previously known candidate genes. Keywords Genome scan · Family study · Gene-environment interaction · Familial combined dyslipidemia · Lipid metabolism Abbreviations BMI: Body mass index · EMHE: EM algorithm based Haseman-Elston regression · FCHL: Familial combined hyperlipidemia · HDL: High-density lipoproteins · IBD: Identity-by- descent · LDL: Low-density lipoproteins · NPL: Nonparametric linkage · PCR: Polymerase chain reaction Introduction It appears likely that in most societies, diet and other en- vironmental factors interact with genetic predisposition for lipid abnormalities to increase the risk of premature heart disease. Both the environmental and genetic factors regulating cholesterol synthesis and degradation have been extensively studied because of interest in the treat- ment of cardiovascular disease. Genes important in cho- lesterol metabolism have been characterized and associa- tions between DNA sequence variation within candidate genes and plasma lipid concentrations examined (e.g., [1, 2, 3, 4, 5, 6]). However, a limitation of the candidate D.R. Reed · R.A. Price ( ✉ ) Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania, 415 Curie Blvd, CRB 135b, Philadelphia, PA 19104, USA e-mail: arlen@bgl.psycha.upenn.edu Tel.: +1-215-8980214, Fax: +1-215-5732041 E. Nanthakumar · M. North · C. Bell Axys Pharmaceuticals, La Jolla, Calif., USA J Mol Med (2001) 79:262–269 DOI 10.1007/s001090100212 ORIGINAL ARTICLE Danielle R. Reed · Elizabeth Nanthakumar Michael North · Callum Bell · R. Arlen Price A genome-wide scan suggests a locus on chromosome 1q21–q23 contributes to normal variation in plasma cholesterol concentration Received: 8 February 2000 / Accepted: 8 February 2001 / Published online: 25 April 2001 © Springer-Verlag 2001 R. ARLEN PRICE Ph.D., is Professor of Psychol- ogy in Psychiatry in the Center for Neurobiology and Behav- ior of the University of Penn- sylvania School of Medicine and Director of the Behavioral Genetics Laboratory. The fo- cus of his work in his labora- tory is on the quantitative and molecular genetics of complex traits, particularly obesity, and mood disorders. DANIELLE R. REED received her Ph.D. in psychol- ogy from Yale University (New Haven, Conn., USA) and did her postdoctoral train- ing in genetics with R. Arlen Price at the Center for Neuro- biology and Behavior, Univer- sity of Pennsylvania. She is presently an Associate Mem- ber at the Monell Chemical Senses Center. Her research interest include the genetics of complex traits in humans and mice, with emphasis on food intake, nutrition and body weight.