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Schizophrenia is a disabling disorder involving genetic predisposition in combination with environmental influences that likely act via dynamic alterations of the epigenome and the transcriptome but its detailed pathophysiology is largely unknown. We performed cell-type specific methylome-wide association study of neonatal blood (N= 333) from individuals who later in life developed schizophrenia and controls. Suggestively significant associations (P< 1.0 × 10−6) were detected in all cell-types and in whole blood with methylome-wide significant associations in monocytes (P= 2.85 × 10−9–4.87 × 10−9), natural killer cells (P= 1.72 × 10−9–7.82 × 10−9) and B cells (P= 3.8 × 10−9). Validation of methylation findings in post-mortem brains (N= 596) from independent schizophrenia cases and controls showed significant enrichment of transcriptional differences (enrichment ratio = 1.98–3.23, P= 2.3 × 10−3–1.0 × 10−5), with specific highly significant differential expression for, for example, BDNF(t = −6.11, P= 1.90 × 10−9). In addition, expression difference in brain significantly predicted schizophrenia (multiple correlation = 0.15–0.22, P = 3.6 × 10−4–4.5 × 10−8). In summary, using a unique design combining pre-disease onset (neonatal) blood methylomic data and post-disease onset (post-mortem) brain transcriptional data, we have identified genes of likely functional relevance that are associated with schizophrenia susceptibility, rather than confounding disease associated artifacts. The identified loci may be of clinical value as a methylation-based biomarker for early detection of increased schizophrenia susceptibility.

Sir.—Jenista and Chapman's1 recommendation to screen all Asian-born adopted children for hepatitis B fails to address important ethical issues. The identification of hepatitis B carrier state carries significant risk and no direct benefit to the adopted child. At present, there is no treatment for hepatitis B carrier state, nor is it possible to prevent or treat complications of hepatitis B.2 On the other hand, the hepatitis screening may cause significant psychosocial harm by stigmatizing individuals and ethnic groups.3 Foreign-born adopted children must deal with numerous psychological issues, but their identification as hepatitis carriers may be the most serious. Already, these children have been refused admission to day-care centers. Both of the children in Jenista and Chapman's study who were in nursery school were excluded after the results of the tests were known. The hysterical response to children with acquired immunodeficiency syndrome and their unjustified exclusion from

To the Editor.—Shaw et al1 advocate using leukocyte esterase-measuring dipsticks for "routine urinalyses" and reading the results at five minutes to increase the sensitivity of detecting abnormal urine sediment. They define abnormal sediment as any red blood cells, casts, yeast, or more than three white blood cells (WBCs) per high-power field. These recommendations are based upon several assumptions regarding the use of clinical tests that need to be examined more closely.The authors have chosen spun-urine microscopy as the "gold standard" for measuring formed elements in the urine. However, for pyuria, spun-urine microscopy is unreliable and correlates poorly with leukocyte excretion rates (number of WBCs per hour) and hemocytometer chamber techniques (number of WBCs per cubic millimeter).2 Leukocyte esterase dipsticks correlate better with pyuria by hemocytometry than by spun-urine microscopy3 and may be more reliable than spun-urine microscopy.The author's definition of abnormal urine sediment appears