Genetic variation that predicts serum lipid levels, specifically total cholesterol, HDL (high density lipoprotein), & LDL (low density lipoprotein).
Phenotype Description & Outline of Project
Find all patients that have had a complete lipid panel, which inc. total serum cholesterol, HDL, & LDL
Find the earliest date each patient had any secondary cause of hyperlipidemia or other factor that affects lipid levels, such as statin medication use Antilipemic medication use Prescription order, fill/refill, or medication list
Abrupt change in lipid level that indicates anti-lipid medication use when all fills not available
Collect all lipid measurements that occur before the exclusions.
Sites Involved / Rough Estimate of Sample Size
At Northwestern, >80% of subjects have a lipid panel with all 3 measures, and ~40% have at least 2 lipid panels that occur before any exclusions. Marshfield reports a similar percentage with eligible lipid panels from their HDL study. Group Health, Mayo, and Vanderbilt have 80-99% of their patients having lab data, and lipid profiles are a relatively common laboratory. Therefore, we estimate having at least 8,000 already genotyped individuals to study.
Scientific Relevance/ Rationale
A few large GWAS studies for lipid levels have recently been reported. Seven loci for HDL-C, 7 for LDL-C and 9 for triglycerides have been reported previously and three very recent studies reported an additional 20 loci. Despite the large number of loci that have been reported to date, as with other common
diseases and traits, these variants account for only a fraction of the heritability, thus leaving most of the heritability yet to be explained and room for additional large studies.
Desired variables (essential for analysis indicated by *)
earliest diagnosis date from cancer/tumor registry, if one exists
**Currently, we’re not requiring that patients meet all the criteria to be a case for type 2 diabetes or hypothyroidism using Northwestern’s & Vanderbilt’s algorithms, respectively; we’re just requiring that they have at least one of the critieria listed, as we’re trying to also capture type 1 diabetics and other forms of hypothyroidism that may affect lipid levels
Niacin, inc. generic names: 'INOSITOL/NIACIN','FOLIC ACID/NIACINAMIDE/CU/ZNOX', 'NIACINAMIDE'
HRT (Hormone Replacement Therapy) or hormonal contraceptives inc. Estrogen/Androgen, at least oral, implant, patch & other forms that are not creams/topical:
ethinyl estradiol, Desogestrel-Ethinyl Estradiol, & other estradiol combinations
Optional NLP used by Marshfield in their HDL algorithm to find Estrogen use:
Earliest mention of the following Estrogen/Androgen drug use in clinical notes (regardless of age or gender) ALORA, CENESTIN, CLIMARA, CLIMARA PRO, COMBIPATCH, DELESTROGEN, ESTRACE, ESTRADERM, ESTRATAB,
Excluded any records where topical or cream was indicated in the flanking text.
Searched the flanking text in records where the drug name='ESTROGEN' for the following terms:
post menopause, post menopause, postmenopausal, on estrogen, went off estrogen, stop estrogen, on unopposed estrogen, estrogen replacement, history of estrogen use, estrogen patch, estrogen usage, estrogen therapy, estrogen pill, unopposed estrogen use, chronic estrogen use.
Kept records where drug name="ESTROGEN" and flanking text contained one of the above terms and there was no indicator of topical or cream in the flanking text.
Type 2 diabetes medications:
Hypothyroidism medications (from Vanderbilt hypothyroidism algorithm for cases):