Table 1.
Summary of Methodological Components for Each SNP-Phenotype Association Analysis in SJLIFE
| Phenotype | Phenotype Transformationa | Unit or Definitiona | GWAS Adjustment Covariatesa | Childhood Cancer Survivor Adjustment Covariatesb | Exclusionsa | Reference Meta-GWASc(PMID) |
|---|---|---|---|---|---|---|
| Anthropometric | ||||||
| Height | sex-standardized Z score | cm | age, ancestry | surgical procedures affecting spinal growth; scoliosis; hypothalamic-pituitary axis tumors; cranial or craniospinal radiation | genetic syndromes, health conditions affecting stature | 25282103, 20881960, 19570815, 19343178, 18391952, 18391951, 18391950 |
| Body mass index (BMI) | inverse normal transformation of residuals | kg/m2; BMI adjusted for amputation | age, age2, sex, ancestry | hypothalamic-pituitary axis tumors; cranial radiation; glucocorticoids | none | 25673413, 24064335, 23669352, 22982992, 20935630, 19079261 |
| Waist-to-hip ratio (WHR) | inverse normal transformation of sex-standardized residuals | ratio of waist and hip circumference (cm) | age, age2, BMI, ancestry | hypothalamic-pituitary axis tumors; cranial radiation; glucocorticoids | none | 28443625, 25673412, 20935629 |
| Blood Pressure | ||||||
| Systolic blood pressure (SBP) | +15 mmHg with use of blood pressure lowering medications | mmHg | age, age2, sex, BMI, ancestry | abdominal, pelvic radiation | prior myocardial infarction or heart failure | 28135244, 28739976, 26390057, 21909115, 19430483, 19430479 |
| Diastolic blood pressure (DBP) | +10 mmHg with use of blood pressure lowering medications | mmHg | age, age2, sex, BMI, ancestry | abdominal, pelvic radiation | prior myocardial infarction or heart failure | same as SBP |
| Blood Lipids | ||||||
| High-density lipoprotein (HDL) | inverse normal transformation of residuals | mg/dL | age, age2, sex, ancestry | hypothalamic-pituitary axis tumors; cranial radiation | use of lipid-lowering medications | 24097068, 19060906 |
| Low-density lipoprotein (LDL) | inverse normal transformation of residuals | mg/dL | age, age2, sex, ancestry | hypothalamic-pituitary axis tumors; cranial radiation | use of lipid-lowering medications | same as HDL |
| Total cholesterol (TC) | inverse normal transformation of residuals | mg/dL | age, age2, sex, ancestry | hypothalamic-pituitary axis tumors; cranial radiation | use of lipid-lowering medications | 24097068 |
| Triglycerides (TG) | inverse normal transformation of residuals | mg/dL | age, age2, sex, ancestry | hypothalamic-pituitary axis tumors; cranial radiation | use of lipid-lowering medications | same as HDL |
| Cardiometabolic Disease | ||||||
| Coronary artery disease (CAD) | none | cases: CTCAE grades ≥ 2 | age, sex, ancestry | BMI; smoking; cardiac-directed radiation; anthracyclines; platinums (cisplatin, carboplatin) | none | 28714975, 26950853, 26343387, 19198609 |
| Type 2 diabetes (T2D) | none | cases: CTCAE grades ≥ 2 | age, sex, BMI, ancestry | cranial radiation; abdominal radiation | none | 28869590, 28566273, 24509480, 20581827, 20418489, 19734900, 18372903 |
| Obesity | none | cases: BMI ≥ 30 kg/m2 | age, sex, ancestry | hypothalamic-pituitary axis tumors; cranial radiation; glucocorticoids | none | 23563607, 21708048 |
Abbreviations: genome-wide association study (GWAS); cm (centimeter); kg (kilogram); m (meter); mmHg (millimeter of mercury); CTCAE (Common Terminology Criteria for Adverse Events, modified v4.03).
Phenotype units and/or definitions and participant exclusion criteria from reference GWAS were reviewed and adapted when necessary for analysis in SJLIFE. GWAS covariates were defined by references.
Covariates specific to childhood cancer survivors, based on the childhood cancer survivorship research literature. Syndromes and health conditions affecting height include: Down syndrome; Turner syndrome; Neurofibromatosis, type 1; Russell-Silver syndrome; benign bone lesion and/or cysts; cartilage disorder; skeletal spine disorder.
Only includes reference GWAS from which summary statistics were compiled, where association statistics for each SNP-phenotype association were taken from the largest, most current study.