Individual olfactory perception reveals meaningful nonolfactory genetic information

Each person expresses a potentially unique subset of ∼400 different olfactory receptor subtypes. Given that the receptors we express partially determine the odors we smell, it follows that each person may have a unique nose; to capture this, we devised a sensitive test of olfactory perception we termed the “olfactory fingerprint.” Olfactory fingerprints relied on matrices of perceived odorant similarity derived from descriptors applied to the odorants. We initially fingerprinted 89 individuals using 28 odors and 54 descriptors. We found that each person had a unique olfactory fingerprint (P < 10−10), which was odor specific but descriptor independent. We could identify individuals from this pool using randomly selected sets of 7 odors and 11 descriptors alone. Extrapolating from this data, we determined that using 34 odors and 35 descriptors we could individually identify each of the 7 billion people on earth. Olfactory perception, however, fluctuates over time, calling into question our proposed perceptual readout of presumably stable genetic makeup. To test whether fingerprints remain informative despite this temporal fluctuation, building on the linkage between olfactory receptors and HLA, we hypothesized that olfactory perception may relate to HLA. We obtained olfactory fingerprints and HLA typing for 130 individuals, and found that olfactory fingerprint matching using only four odorants was significantly related to HLA matching (P < 10−4), such that olfactory fingerprints can save 32% of HLA tests in a population screen (P < 10−6). In conclusion, a precise measure of olfactory perception reveals meaningful nonolfactory genetic information.

Design of Early Validation Trials of Biomarkers

The design of early-phase studies of putative screening markers in clinical populations is discussed. Biological, epidemiological, statistical and computational issues all affect the design of early-phase studies of these markers, but there are frequently little or no data in hand to facilitate the design. Early-phase studies must be designed as part of a development program, considering the final use of the marker, directly informing the decision to made at the study's conclusion. Therefore, they should test for sensitivity and specificity that would be minimally acceptable to proceed to the next stage of development. Designing such trials requires explicit assumptions about prevalence and false positive and negative costs in the ultimate target population. Early discussion of these issues strengthens the development process, since enthusiasm for developing technologies is balanced by realism about the requirements of a valid population screen. Receiver operating characteristic (ROC) curves, which are useful descriptive tools, may be misleading when evaluating tests in low-prevalence populations, because they emphasize the relationship between specificity and sensitivity in the range of specificity likely to be too low to be useful in mass screening applications.

The Gospel Oak Study stage IV: the clinical relevance of subjective memory impairment in older people

SYNOPSISThe prevalence rate of subjective memory impairment (SMI) and its value as a predictor of future depression or dementia was studied in a community sample of elderly residents in one electoral ward using the short-CARE. SMI was found to be common, occurring in 25% of subjects. Subjects with SMI were more likely to be suffering from either dementia or depression than those without the complaint, although 60% of subjects with SMI did not have evidence of either disorder. When followed up over a 2-year period, subjects with SMI were found to be at four-fold greater risk of developing future dementia and two-fold greater risk of developing a depression compared with those without SMI. The SMI scale was not found to be useful as a population screen for dementia or depression, although two of the nine items might have value as screening questions in clinical circumstances to determine those with memory complaints at risk for dementia.

Selective Screening of Hospitalized Patients for the Presence of Asymptomatic Hepatitis B Virus Carriage: Predictability Based on Census Tract Data

Review of all hepatitis B surface antigen-positive patients reported to the county health department over the past 3 years showed that 60% of patients had been diagnosed at our hospital, which serves an inner city, predominantly black, indigent population. Sera from 524 adult patients admitted to the hospital were prospectively collected and tested for hepatitis B surface antigen, eight (1.5%) of which were antigen-positive. Census tract data allowed us to perform selective screening of sera from 95 other patients who were subsequently hospitalized and deemed “high risk” for hepatitis B infection. Nine of 95 (9.5%) selectively screened samples were positive for hepatitis B surface antigen, which represented a significantly higher rate of antigen carriage (P<0.0001) in hospitalized patients from “high risk” areas than that found in the general population screen. The methodology presented herein may be useful in providing a means of identifying hepatitis B surface antigen-positive patients from adult, urban, indigent care populations.