Linkage analysis of diabetes status among hypertensive families. The hypertension genetic epidemiology network study

• Published in: Diabetes (New York, N.Y.) Vol. 53; no. 12; pp. 3307 - 3312
• Main Authors: AVERY, Christy L, FREEDMAN, Barry I, HUNT, Steven C, ALMASY, Laura, NORTH, Kari E, HEISS, Gerardo, KRAJA, Aldi, RICE, Treva, ARNETT, Donna, MILLER, Michael B, PANKOW, James S, LEWIS, Cora E, MYERS, Richard H
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01-12-2004
• Subjects: African Americans; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Body fat; Cardiology. Vascular system; Care and treatment; Chromosome Mapping; Chromosomes; Continental Population Groups; Cookery for hypertensives; Diabetes; Diabetes Mellitus, Type 2 - epidemiology; Diabetes Mellitus, Type 2 - genetics; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - epidemiology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Epidemiology; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Experimental diseases; Families & family life; Female; Genes; Genome, Human; Genomes; Humans; Hypertension; Hypertension - epidemiology; Hypertension - genetics; Male; Medical sciences; Middle Aged; Risk factors; Type 2 diabetes; United States; White people; United States; Endocrinopathy; Hypertension; Diabetes mellitus; Genetic linkage; Cardiovascular disease; Genetics; Epidemiology
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/diabetes.53.12.3307

Type 2 diabetes susceptibility is determined by multiple genetic and environmental factors. Genome-wide linkage scans have localized common regions, possibly harboring susceptibility genes on chromosomes 1, 2, 12, and 20. Variability in linkage findings underscores the probable genetic heterogeneity of type 2 diabetes. Thus, we conducted a genome scan of diabetes status using maximum likelihood methods that model affection status by a liability threshold model. Hypertensive sibships and their offspring and/or parents in the Hypertension Genetic Epidemiology Network study were recruited from five field centers. The diabetes phenotype was derived using the World Health Organization criteria and adjusted for race/study center, age, age2, sex, and with and without percent body fat. In total, 567 diabetic participants were identified in 437 families. Variance component linkage analysis was performed among 1,545 Caucasians and 1,608 African Americans using race-specific marker allele frequencies. We detected a quantitative trait loci (QTLs) influencing diabetes variance (logarithm of odds = 3.4) on chromosome 22, which overlaps a positive type 2 diabetes finding among Canadian Oji-Cree Indians. We also observed suggestive evidence for linkage on chromosomes 1, 2, 5, 8, 14, 17, and 19. The identification and replication of type 2 diabetes QTLs will bring us closer to the detection of functional genes that influence diabetes susceptibility.