TY - JOUR
T1 - The study of interactions between genome and exposome in the development of systemic lupus erythematosus
AU - Leffers, Henrik Christian Bidstrup
AU - Lange, Theis
AU - Collins, Christopher
AU - Ulff-Møller, Constance Jensina
AU - Jacobsen, Søren
N1 - Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2019/4
Y1 - 2019/4
N2 - Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by a broad spectrum of clinical and serological manifestations. This may reflect a complex and multifactorial etiology involving several identified genetic and environmental factors, though not explaining the full risk of SLE. Established SLE risk genotypes are either very rare or with modest effect sizes and twin studies indicate that other factors besides genetics must be operative in SLE etiology. The exposome comprises the cumulative environmental influences on an individual and associated biological responses through the lifespan. It has been demonstrated that exposure to silica, smoking and exogenous hormones candidate as environmental risk factors in SLE, while alcohol consumption seems to be protective. Very few studies have investigated potential gene-environment interactions to determine if some of the unexplained SLE risk is attributable hereto. Even less have focused on interactions between specific risk genotypes and environmental exposures relevant to SLE pathogenesis. Cohort and case-control studies may provide data to suggest such biological interactions and various statistical measures of interaction can indicate the magnitude of such. However, such studies do often have very large sample-size requirements and we suggest that the rarity of SLE to some extent can be compensated by increasing the ratio of controls. This review summarizes the current body of knowledge on gene-environment interactions in SLE. We argue for the prioritization of studies that comprise the increasing details available of the genome and exposome relevant to SLE as they have the potential to disclose new aspects of SLE pathogenesis including phenotype heterogeneity.
AB - Systemic lupus erythematosus (SLE) is a systemic inflammatory autoimmune disease characterized by a broad spectrum of clinical and serological manifestations. This may reflect a complex and multifactorial etiology involving several identified genetic and environmental factors, though not explaining the full risk of SLE. Established SLE risk genotypes are either very rare or with modest effect sizes and twin studies indicate that other factors besides genetics must be operative in SLE etiology. The exposome comprises the cumulative environmental influences on an individual and associated biological responses through the lifespan. It has been demonstrated that exposure to silica, smoking and exogenous hormones candidate as environmental risk factors in SLE, while alcohol consumption seems to be protective. Very few studies have investigated potential gene-environment interactions to determine if some of the unexplained SLE risk is attributable hereto. Even less have focused on interactions between specific risk genotypes and environmental exposures relevant to SLE pathogenesis. Cohort and case-control studies may provide data to suggest such biological interactions and various statistical measures of interaction can indicate the magnitude of such. However, such studies do often have very large sample-size requirements and we suggest that the rarity of SLE to some extent can be compensated by increasing the ratio of controls. This review summarizes the current body of knowledge on gene-environment interactions in SLE. We argue for the prioritization of studies that comprise the increasing details available of the genome and exposome relevant to SLE as they have the potential to disclose new aspects of SLE pathogenesis including phenotype heterogeneity.
KW - Case-Control Studies
KW - Environmental Exposure/adverse effects
KW - Gene-Environment Interaction
KW - Genetic Predisposition to Disease
KW - Genome, Human/physiology
KW - Genotype
KW - Humans
KW - Lupus Erythematosus, Systemic/epidemiology
U2 - 10.1016/j.autrev.2018.11.005
DO - 10.1016/j.autrev.2018.11.005
M3 - Review
C2 - 30772495
SN - 1568-9972
VL - 18
SP - 382
EP - 392
JO - Autoimmunity Reviews
JF - Autoimmunity Reviews
IS - 4
ER -