An Autosomal Genome-wide Scan for Loci Linked to Pre-Diabetic Phenotypes in Nondiabetic Chinese Subjects From the Stanford Asia-Pacific Program of Hypertension and Insulin Resistance Family Study
- Yen-Feng Chiu1,
- Lee-Ming Chuang23,
- Chin-Fu Hsiao1,
- Yi-Jen Hung4,
- Ming-Wei Lin5,
- Ying-Tsung Chen6,
- John Grove7,
- Eric Jorgenson8,
- Thomas Quertermous9,
- Neil Risch8 and
- Chao A. Hsiung1
- 1Division of Biostatistics and Bioinformatics, National Health Research Institutes, Taipei, Taiwan
- 2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- 3Graduate Institute of Clinical Medicine, National Taiwan University, Taipei, Taiwan
- 4Division of Endocrinology and Metabolism, Tri-Service General Hospital, Taipei, Taiwan
- 5Faculty of Medicine, School of Medicine, National Yang-Ming University and Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan
- 6Executive Office, Taichung Veterans General Hospital, Taichung, Taiwan
- 7Department of Public Health Sciences and Epidemiology, John A. Burns School of Medicine, University of Hawaii and Pacific Health Research Institute, Honolulu, Hawaii
- 8Department of Genetics, Stanford University School of Medicine, Stanford, California
- 9Stanford University School of Medicine, Stanford, California
- Address correspondence and reprint requests to Chao A. Hsiung, PhD, Division of BiostatisticsBioinformatics, National Health Research Institutes, 35, Keyan Rd., Zhunan, Miaohi, Taiwan. E-mail: hsiung{at}nhri.org.tw
Abstract
Type 2 diabetes is a complex disease involving both genetic and environmental components. Abnormalities in insulin secretion and insulin action usually precede the development of type 2 diabetes and can serve as good quantitative measures for genetic mapping. We therefore undertook an autosomal genomic search to locate the quantitative trait locus (QTL) linked to these traits in 1,365 nondiabetic Chinese subjects from 411 nuclear families. Residuals of these log-transformed quantitative traits were analyzed in multipoint linkage analysis using a variance-components approach. The most significant QTL for fasting insulin, which coincides with the QTL for homeostasis model assessment of insulin resistance, was located at 37 cM on chromosome 20, with a maximum empirical logarithm of odds (LOD) score of 3.01 (empirical P = 0.00006) when adjusted for age, sex, BMI, antihypertensive medications, recruitment centers, and environmental factors. In the same region, a QTL for fasting glucose was identified at 51 cM, with an empirical LOD score of 2.03 (empirical P = 0.0012). There were other loci with maximum empirical LOD scores ≥1.29 located on chromosomes 1q, 2p, 5q, 7p, 9q, 10p, 14q, 18q, and 19q for different diabetes-related traits. These loci may harbor genes that regulate glucose homeostasis either independently or via interactions of the genes within these regions.
- AUC, area under the curve
- HOMA, homeostasis model assessment
- HOMA-β, HOMA of β-cell function
- HOMA-IR, HOMA of insulin resistance
- LOD, logarithm of odds
- QTL, quantitative trait locus
- SAPPHIRe, Stanford Asia-Pacific Program of Hypertension and Insulin Resistance
Footnotes
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Y.-F.C. and L.-M.C. contributed equally to this work.
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- Accepted January 4, 2005.
- Received July 10, 2004.
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