Bivariate mixture modeling of transferrin saturation

Bivariate mixture modeling was used to analyze joint population distributions of transferrin saturation (TS) and serum Ferritin concentration (SF) measured in the Hemochromatosis and Iron Overload Screening (HEIRS) Study.

Four components (C1, C2, C3, and C4) with successively age-adjusted increasing means for transferrin saturation and serum ferritin were identified in data from 26,832 African Americans, 12,620 Asians, 12,264 Hispanics, and 43,254 whites. The largest component, C2, had normal mean transferrin saturation Transferrin (21% to 26% for women, 29% to 30% for men) and Serum ferritin (43–82 μg/L for women, 165–242 μg/L for men), which consisted of component proportions greater than 0.59 for women and greater than 0.68 for men. C3 and C4 had progressively greater mean values for transferrin saturation and serum ferritin with progressively lesser component proportions.

C1 had mean Transferrin Saturation values less than 16% for women (<20% for men) and SF values less than 28 μg/L for women (<47 μg/L for men). Compared with C2, adjusted odds of iron deficiency were significantly greater in C1 (14.9–47.5 for women, 60.6–3530 for men), adjusted odds of liver disease were significantly greater in C3 and C4 for African-American women and all men, and adjusted odds of any HFE mutation were increased in C3 (1.4–1.8 for women, 1.2–1.9 for men) and in C4 for Hispanic and white women (1.5 and 5.2, respectively) and men (2.8 and 4.7, respectively). Joint mixture modeling identifies a component with lesser serum ferritin and transferrin saturation at risk for iron deficiency and 2 components with greater SF and TS at risk for liver disease or HFE mutations . This approach can identify populations in which hereditary or acquired factors influence metabolism measurement.

Abbreviations: EM, expectation-maximization; HFE, hemochromatosis gene on chromosome 6p; HEIRS, Hemochromatosis and Iron Overload Screening; SF, serum ferritin concentration; TS, transferrin saturation; wt, wild type

The HEIRS Study was initiated and funded by NHLBI in conjunction with NHGRI. Supported by contracts N01-HC-05185 ( University of Minnesota), N01-HC-05186 (Howard University ), N01-HC-05188 (University of Alabama at Birmingham), N01-HC-05189 (Kaiser Permanente Center for Health Research), N01-HC-05190 (University of California, Irvine), N01-HC-05191 (London Health Sciences Centre), and N01-HC-05192 (Wake Forest University). Also supported by Grant R01 HL083328-01A1 from the National Heart, Lung, and Blood Institute (to C.E.M.); Grant M01-RR00032 from the University of Alabama at Birmingham General Clinical Research Center (GCRC); the Southern Iron Disorders Center (to J.C.B.); Grant M01-RR10284 from Howard University GCRC; Howard University Research Scientist Award UH1-HL03679-05 from the National Heart, Lung, and Blood Institute and the Office of Research on Minority Health (to V.R.G.); and Grant UC Irvine M01RR 00827-29 from the General Clinical Research Centers Program of the National Center for Research Resources National Institutes of Health.