dissecting cis regulation of gene expression in human metabolic tissues解剖顺式调节基因表达在人类代谢组织.pdfVIP

Dissecting Cis Regulation of Gene Expression in Human Metabolic Tissues 1 ¤ 2 1 1 3 4 Radu Dobrin * , Danielle M.Greenawalt , Guanghui Hu , Daniel M. Kemp , Lee M. Kaplan , Eric E. Schadt , Valur Emilsson5 1 Merck Research Laboratories, Rahway, New Jersey, United States of America, 2 Merck Research Laboratories, Boston, Massachusetts, United States of America, 3 Massachusetts General Hospital, Boston, Massachusetts, United States of America, 4 Pacific Biosciences, Menlo Park, California, United States of America, 5 Icelandic Heart Association, Kopavogur, Iceland Abstract Complex diseases such as obesity and type II diabetes can result from a failure in multiple organ systems including the central nervous system and tissues involved in partitioning and disposal of nutrients. Studying the genetics of gene expression in tissues that are involved in the development of these diseases can provide insights into how these tissues interact within the context of disease. Expression quantitative trait locus (eQTL) studies identify mRNA expression changes linked to proximal genetic signals (cis eQTLs) that have been shown to affect disease. Given the high impact of recent eQTL studies, it is important to understand what role sample size and environment plays in identification of cis eQTLs. Here we show in a genotyped obese human population that the number of cis eQTLs obey precise scaling laws as a function of sample size in three profiled tissues, i.e. omental adipose, subcutaneous adipose and liver. Also, we show that genes (or transcripts) with cis eQTL associations detected in a small population are detected at approximately 90% rate in the largest population available for our study, indicating that genes with st