Estimating relative risk of a log‐transformed exposure measured in pools

Pooling biospecimens prior to performing laboratory assays is a useful tool to reduce costs, achieve minimum volume requirements and mitigate assay measurement error. When estimating the risk of a continuous, pooled exposure on a binary outcome, specialized statistical techniques are required. Current methods include a regression calibration approach, where the expectation of the individual-level exposure is calculated by adjusting the observed pooled measurement with additional covariate data. While this method employs a linear regression calibration model, we propose an alternative model that can accommodate log-linear relationships between the exposure and predictive covariates. The proposed model permits direct estimation of the relative risk associated with a log-transformation of an exposure measured in pools. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

[1]  Ramzi W. Nahhas,et al.  Leptin is inversely related to age at menarche in human females. , 1997, The Journal of clinical endocrinology and metabolism.

[2]  H. White.  Maximum Likelihood Estimation of Misspecified Models , 1982 .

[3]  M. J. Vazquez,et al.  Roles of leptin in reproduction, pregnancy and polycystic ovary syndrome: consensus knowledge and recent developments. , 2015, Metabolism: clinical and experimental.

[4]  Robert H Lyles,et al.  A highly efficient design strategy for regression with outcome pooling , 2014, Statistics in medicine.

[5]  M. Bassett,et al.  Pooling of sera for human immunodeficiency virus (HIV) testing: an economical method for use in developing countries. , 1988, Journal of clinical pathology.

[6]  R. Fan,et al.  An updated view of leptin on implantation and pregnancy: a review. , 2014, Physiological research.

[7]  S. Bandinelli,et al.  The association between leptin and depressive symptoms is modulated by abdominal adiposity , 2014, Psychoneuroendocrinology.

[8]  P. Sly,et al.  Pooled biological specimens for human biomonitoring of environmental chemicals: Opportunities and limitations , 2014, Journal of Exposure Science and Environmental Epidemiology.

[9]  Mary T. Brinkoetter,et al.  Early life adversity is associated with elevated levels of circulating leptin, irisin, and decreased levels of adiponectin in midlife adults. , 2014, The Journal of clinical endocrinology and metabolism.

[10]  A. Calafat,et al.  Perfluorinated chemicals in selected residents of the American continent. , 2006, Chemosphere.

[11]  G. Parham,et al.  HPV screening for cervical cancer in rural India. , 2009, The New England journal of medicine.

[12]  Robert H Lyles,et al.  Semiparametric regression models for a right-skewed outcome subject to pooling. , 2015, American journal of epidemiology.

[13]  Enrique F Schisterman,et al.  Pooling biospecimens and limits of detection: effects on ROC curve analysis. , 2006, Biostatistics.

[14]  Enrique F Schisterman,et al.  A randomised trial to evaluate the effects of low-dose aspirin in gestation and reproduction: design and baseline characteristics. , 2013, Paediatric and perinatal epidemiology.

[15]  J. Felix,et al.  HPV screening for cervical cancer in rural India. , 2009, The New England journal of medicine.

[16]  V. Bini,et al.  Leptin serum levels in normal weight and obese children and adolescents: relationship with age, sex, pubertal development, body mass index and insulin , 1997, International Journal of Obesity.

[17]  E. J. Dick,et al.  Beyond ‘lognormal versus gamma’: discrimination among error distributions for generalized linear models , 2004 .

[18]  Li Tang,et al.  Likelihood‐based methods for regression analysis with binary exposure status assessed by pooling , 2012, Statistics in medicine.

[19]  C R Weinberg,et al.  Using Pooled Exposure Assessment to Improve Efficiency in Case‐Control Studies , 1999, Biometrics.

[20]  G. Jensen,et al.  Leptin, not adiponectin, predicts hypertension in the Copenhagen City Heart Study. , 2010, American journal of hypertension.

[21]  Aijun Ye,et al.  Assessment of skewed exposure in case‐control studies with pooling , 2012, Statistics in medicine.

[22]  N. Perkins,et al.  Serum leptin levels and reproductive function during the menstrual cycle. , 2014, American journal of obstetrics and gynecology.

[23]  B. Kubanek,et al.  Mini‐pool screening by nucleic acid testing for hepatitis B virus, hepatitis C virus, and HIV: preliminary results , 1998, Transfusion.

[24]  Enrique F Schisterman,et al.  Roc Curve Analysis for Biomarkers Based on Pooled Assessments , 2022 .

[25]  C. Hsieh,et al.  Pooling Strategies for Screening Blood in Areas with Low Prevalence of HIV , 1993 .

[26]  Zhiwei Zhang,et al.  Binary Regression Analysis with Pooled Exposure Measurements: A Regression Calibration Approach , 2011, Biometrics.

[27]  M. Bates,et al.  Persistent organochlorines in the serum of the non-occupationally exposed New Zealand population. , 2004, Chemosphere.

[28]  Albert Vexler,et al.  A combined efficient design for biomarker data subject to a limit of detection due to measuring instrument sensitivity , 2011, 1202.6524.

[29]  B. Grant,et al.  Statistical modeling of volume of alcohol exposure for epidemiological studies of population health: the US example , 2010, Population health metrics.

[30]  Robert H Lyles,et al.  Positing, fitting, and selecting regression models for pooled biomarker data , 2015, Statistics in medicine.

[31]  W. Stahel,et al.  Log-normal Distributions across the Sciences: Keys and Clues , 2001 .

[32]  Clarice R Weinberg,et al.  Specimen pooling for efficient use of biospecimens in studies of time to a common event. , 2013, American journal of epidemiology.

[33]  R. Schutte,et al.  Leptin is Positively Associated with Blood Pressure in African Men with a Low Body Mass Index: The SAfrEIC Study , 2014, Hormone and Metabolic Research.

[34]  N. Draper,et al.  Applied Regression Analysis: Draper/Applied Regression Analysis , 1998 .

[35]  Edward A. McBean,et al.  Statistical procedures for analysis of environmental monitoring data and risk assessment , 2000 .

[36]  Ganapati P. Patil,et al.  The gamma distribution and weighted multimodal gamma distributions as models of population abundance , 1984 .

[37]  N. Draper,et al.  Applied Regression Analysis. , 1967 .

[38]  Zumin Shi,et al.  Association between Serum Leptin Concentrations and Insulin Resistance: A Population-Based Study from China , 2013, PloS one.

[39]  P. Whincup,et al.  Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease. , 2007, Atherosclerosis.

[40]  R A Irizarry,et al.  On the utility of pooling biological samples in microarray experiments. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[41]  S Vansteelandt,et al.  Regression Models for Disease Prevalence with Diagnostic Tests on Pools of Serum Samples , 2000, Biometrics.

[42]  G. Zou,et al.  A modified poisson regression approach to prospective studies with binary data. , 2004, American journal of epidemiology.

[43]  Albert Vexler,et al.  To pool or not to pool, from whether to when: applications of pooling to biospecimens subject to a limit of detection. , 2008, Paediatric and perinatal epidemiology.

[44]  R. Considine,et al.  Serum immunoreactive-leptin concentrations in normal-weight and obese humans. , 1996, The New England journal of medicine.

[45]  Haibo Zhou,et al.  Outcome-Dependent Sampling: An Efficient Sampling and Inference Procedure for Studies With a Continuous Outcome , 2007, Epidemiology.

[46]  C. Mantzoros,et al.  Narrative Review: The Role of Leptin in Human Physiology: Emerging Clinical Applications , 2010, Annals of Internal Medicine.