Defining an Obesity QTL on Chromosome 3q

To investigate the genetic basis of obesity by fine mapping an obesity quantitative trail linkage (QTL) linked to chromosome 3q.

Study Overview

• Status: Completed
• Conditions: Heart Diseases; Cardiovascular Diseases; Obesity

Detailed Description

BACKGROUND:

In the last several decades obesity has emerged as a major public health threat. While prevention through lifestyle change is the only long-term solution, better understanding of the physiologic mechanisms would greatly assist development of drugs and targeted prevention. Obesity is a highly heritable condition and while genes must account for a substantial proportion of individual susceptibility they have eluded detection. Powerful new genetic and genomic tools now permit comprehensive evaluation of candidate genes, including all genes under linkage peaks. These tools include new genomic resources (the human genome sequence, databases of common SNPs, and the haplotype map), rapid and inexpensive discovery and genotyping and new analytic methods (haplotype-based association and admixture mapping).

DESIGN NARRATIVE:

In a large African American family set Dr. Zhu and colleagues have obtained strong linkage evidence for obesity on chromosome 3q (combined LOD score = 3.7). A prime candidate (adiponectin) lies near this peak. They propose to follow up that finding by combining the epidemiologic data with high-throughput genotyping and move from linkage to association analysis. The results for this QTL will be evaluated within the available environmental factors to assess potential gene-environment and gene-gene interactions. The available phenotypes include body composition, resting metabolic rate, physical activity, plasma insulin, glucose, and leptin. In a family-based design they will examine the linkage peak centered on position 188 cM on chromosome 3q (20 Cm 1-LOD support interval), with the following step-wise strategy: (a) Genotype 200 single nucleotide polymorphisms (SNPs) in this region on 300 families (1,000 individuals); (b) Conduct linkage, linkage disequilibrium and admixture mapping to potentially further narrow the region; and (c) Conduct resequencing and haplotype-based association studies for all candidate genes under the peak. Statistical analysis incorporating intermediate phenotypes and environmental covariates will be used to characterize potential gene x gene or gene x environment interactions. Replication will be tested in additional populations of African and European origin.

• Study Type: Observational
• Enrollment (Actual): 1931

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Maywood cohort DNA samples were obtained from a larger cohort of families enrolled in the studies of blood pressure at Loyola University in Maywood, IL. The survey enrolled a representative random sample of the population between the ages of 18 and 74, regardless of obesity phenotype. A subcohort of 775 unrelated participants was selected and oversampled at the upper and lower ends of the BMI distribution to increase the power.

Nigerian cohort Study participants were recruited from Igbo-Ora and Ibadan in southwest Nigeria as part of a long-term study on the environmental and genetic factors underlying hypertension. The sample comprised 1098 unrelated adults with normal or elevated blood pressure and 155 unrelated participants from Ibadan with elevated blood pressure recruited as controls in the Africa-America Diabetes Mellitus (AADM) study.

Description

The survey enrolled a representative random sample of the population the age of 18 and 74, regardless of obesity phenotype.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Maywood; The were 743 subjects were sampled from Maywood, Il. There was no intervention.
Nigeria; There were 1188 Nigerian sampled from Igbo-Ora and Ibadan, Nigeria. There was no intervention.

Collaborators and Investigators

• Sponsor: Case Western Reserve University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Xiaofeng Zhu, Case Western Reserve University

Study record dates

Study Major Dates

• Study Start: July 1, 2004
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): May 1, 2008

Study Registration Dates

• First Submitted: July 15, 2004
• First Submitted That Met QC Criteria: July 16, 2004
• First Posted (Estimate): July 19, 2004

Study Record Updates

• Last Update Posted (Actual): February 23, 2022
• Last Update Submitted That Met QC Criteria: February 7, 2022
• Last Verified: July 1, 2008

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Heart Diseases; Cardiovascular Diseases; Obesity
• Other Study ID Numbers: 1263; R01HL074166 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No