ABSTRACT
Genomic medicine research requires substantial time and resources to obtain phenotype data. The electronic health record offers potential efficiencies in addressing these temporal and economic challenges, but few studies have explored the feasibility of using such data for genetics research. The main objective of this study was to determine the association of two genetic variants located on chromosome 9p21 conferring susceptibility to coronary heart disease and type 2 diabetes with a variety of clinical phenotypes derived from the electronic health record in a population of morbidly obese patients. Data on more than 100 clinical measures including diagnoses, laboratory values, and medications were extracted from the electronic health records of a total of 709 morbidly obese (body mass index (BMI) >/= 40 kg/m(2)) patients. Two common single nucleotide polymorphisms located at chromosome 9p21 recently linked to coronary heart disease and type 2 diabetes (McPherson et al. Science 316:1488-1491, 2007; Saxena et al. Science 316:1331-1336, 2007; Scott et al. Science 316:1341-1345, 2007) were genotyped to assess statistical association with clinical phenotypes. Neither the type 2 diabetes variant nor the coronary heart disease variant was related to any expected clinical phenotype, although high-risk type 2 diabetes/coronary heart disease compound genotypes were associated with several coronary heart disease phenotypes. Electronic health records may be efficient sources of data for validation studies of genetic associations.
ABSTRACT
OBJECTIVE: To determine whether 2 single nucleotide polymorphisms (SNPs) in the obesity genes the fat mass and obesity associated gene (FTO) and the insulin induced gene 2 (INSIG2) are associated with class III, or morbid, obesity in patients undergoing bariatric weight loss operations. DESIGN: Retrospective analysis of genotype and clinical data. SETTING: Large rural tertiary care health system. PATIENTS: A total of 707 adult patients with a body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of at least 40 undergoing open or laparoscopic Roux-en-Y gastric bypass operations for morbid obesity or its comorbid medical problems at Geisinger Medical Center, Danville, Pennsylvania. RESULTS: The mean BMI in the predominantly white female cohort was 51.2. Approximately 21% of patients were homozygous for the FTO obesity SNP variant, 13% were homozygous for the INSIG2 obesity SNP variant, and 3.4% were homozygous for both. Mean BMIs in the groups homozygous for each of these genes were not significantly different from nonhomozygotes. However, FTO/INSIG2 double homozygotes and homozygote/heterozygote pairs had significantly higher BMIs than the other groups. CONCLUSION: Increased BMI in morbid obesity is associated with a combination of FTO and INSIG2 SNPs.
