speciation. Cu, Se, and Zn can be measured in plasma or erythrocytes (Vitoux et al. 1999), although erythrocyte Cu, Se, and Zn have the advantage of being less affected by the acute- phase response associated with inflammation or infections (Oakes et al. 2008). Subject characteristics and socioeco‑ nomic effects. As we expected, sex, age, and tobacco or alcohol use were significantly asso- ciated with several elements [Supplemental M a t e r i a l , T a b l e 2 ( d o i : 1 0 . 1 2 8 9 / e h p . 0901541)]. The most striking was a 3-fold increase in erythrocyte Cd in smokers com- pared with nonsmokers, which has been well documented (Grasmick et al. 1985; Moreau et al. 1983) and ascribed to selective Cd uptake by Nicotiana species (Lugon-Moulin et al. 2006). Cd concentration was also associ- ated with sex (women had higher values) and educational level (higher levels of education were associated with lower values). Genetic effects on trace elements The quantity of alcohol consumed in the week before blood collection, as assessed from self-report of drinking, was positively associated with As, Hg, Pb, and Se concen- trations [Supplemental Material, Figure 1 (doi:10.1289/ehp.0901541)]. There was also an apparent effect of alcohol on Cd, which may be due to the association between alcohol use and smoking; the association with alcohol was absent after adjusting for smoking status (Supplemental Material, Table 2). We expected to find an association of alco- hol with Pb based on results of other studies (Grandjean et al. 1981; Grasmick et al. 1985; Hense et al. 1992; Shaper et al. 1982) and our previous analysis of these data (Whitfield et al. 2007). However, there is little compa- rable information on the effects of alcohol on As or Hg. In a study on urinary As, Vahter and Lind (1986) found no effect of alcohol use, and in a study on urinary Hg in Hg-exposed Chromosome 2 Using erythrocytes as a relevant and acces- sible model tissue, we identified genetic varia- tion through use of twin data, comparing the similarity of members of MZ and DZ twin pairs. Where possible, we identified chromo- somal locations of relevant genes through link- age analysis. Along with this genetic focus, we evaluated the effects of individual and socio- economic factors. Incorporation of such effects in the data analysis also increases the power to detect and evaluate genetic effects. We found that genetic variation plays a significant role in determining concentrations of the measured elements, and some significant or suggestive genetic loci were identified by linkage analysis. Many methods have been used to assess trace and toxic element status, although some are not applicable to humans. Easily available human materials that have been used previ- ously are blood, urine, and hair, each of which has its uses and limitations. The primary limi- tation of the present study is that our results relate only to the concentration of measured elements in erythrocytes. For Pb, this is not a problem; measuring blood Pb is the standard procedure for evaluating current and recent exposure, and essentially all the Pb in blood is bound to erythrocytes. Plasma or serum Pb is < 1% of blood Pb (Manton et al. 2001; Schutz et al. 1996). Pb is not only bound to the erythrocytes, but also has direct effects on erythropoiesis, which can lead to anemia. For Cd, studies on Cd distribution in experimen- tal animals show that injected Cd redistrib- utes from the plasma to erythrocytes, and after 48 hr, erythrocyte Cd concentration is about 20 times the plasma concentration (Friberg et al. 1974). For Hg and As, the distribution between erythrocytes and plasma and the usefulness of urine measurements depend on 414 pairs 501 pairs 5 4 e 3 r o c s D O L 2 1 0 0 e r o c s D O L e r o c s D O L 3 2 1 0 3 2 1 0 50 50 Zn Se Cd × Cu Zn Se 100 150 200 250 Genetic distance (cM) Chromosome 4 Environmental Health Perspectives • volume 118 | number 6 | June 2010 779 25 50 75 100 125 Genetic distance (cM) Figure 1. Details of linkage for Pb on chromo- some 3. The increased number of DZ twin pairs [from 414 pairs reported previously (Whitfield et al. 2007) to 501] increased the peak LOD (logarithm of odds) score at 50 cM from 2.63 to 4.21. 100 150 200 Genetic distance (cM) Figure 2. Linkage results for chromosomes 2 (A) and 4 (B), comparing results across elements. The hori- zontal line shows the suggestive LOD (logarithm of odds) threshold of 1.6.