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Smoking is associated with, but does not cause, depressed mood in pregnancy--a mendelian randomization study.

ABSTRACT: Smokers have a higher prevalence of major depressive episodes and depressive symptoms than the general population, but whether this association is causal, or is due to confounding or reverse causation is uncertain because of the problems inherent in some epidemiological studies. Mendelian randomization, in which a genetic variant is used as a surrogate for measuring exposure, is an approach which may be used to better understand this association. We investigated the rs1051730 single nucleotide polymorphism in the nicotine acetylcholine receptor gene cluster (CHRNA5-CHRNA3-CHRNB4), associated with smoking phenotypes, to determine whether women who continued to smoke were also more likely to report a low mood during pregnancy. We found among women who smoked pre-pregnancy, those with the 1051730 T allele smoked more and were less likely to quit smoking during pregnancy, but were also less likely to report high levels of depressed mood at 18 weeks of pregnancy (per allele OR?=?0.84, 95%CI 0.72 to 0.99, p?=?0.034). The association between genotype and depressed mood was limited to women who were smokers prior to pregnancy, with weak evidence of an interaction between smoking status and genotype (p?=?0.07). Our results do not support a causal role of smoking on depressed mood, but are consistent with a self-medication hypothesis, whereby smoking is used to alleviate symptoms of depression. A replication study using multiple genetic variants which influence smoking via different pathways is required to confirm these findings and provide evidence that the genetic variant is reflecting the effect of quitting smoking on depressed mood, and is not directly affecting mood.

SUBMITTER: Lewis SJ

PROVIDER: S-EPMC3139580 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Smoking is associated with, but does not cause, depressed mood in pregnancy--a mendelian randomization study.

Lewis Sarah J SJ Araya Ricardo R Smith George Davey GD Freathy Rachel R Gunnell David D Palmer Tom T Munafò Marcus M

PloS one 20110719 7

Smokers have a higher prevalence of major depressive episodes and depressive symptoms than the general population, but whether this association is causal, or is due to confounding or reverse causation is uncertain because of the problems inherent in some epidemiological studies. Mendelian randomization, in which a genetic variant is used as a surrogate for measuring exposure, is an approach which may be used to better understand this association. We investigated the rs1051730 single nucleotide p ...[more]

PMID: 21818261

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Project description:ObjectiveLow back pain is a prevalent and debilitating condition worldwide, with significant implications for individuals' quality of life and productivity. The aim of this study was to assess the relationship between mood instability and the risk of developing chronic low back pain, using a rigorously designed mendelian randomization methodology.MethodThe study incorporated both univariate and multivariate mendelian randomization to analysis the causal relationship between mood instability and the risk of developing chronic low back pain. The data on mood instability from the Integrative Epidemiology Unit (IEU) opened Genome-Wide Association Studies (GWAS) project (IEU-opened GWAS project). Data on low back pain were collected from two sources: One source is the IEU open GWAS project (discovery data). Another source is a GWAS meta-analysis (replication data). Inverse variance weighted method, weighted median method, MR-Egger regression, and mendelian randomization pleiotropy residual sum and outlier method were used for mendelian randomization analysis.ResultThe univariable mendelian randomization analysis shows a statistically significant correlation between mood instability and the risk of low back pain. Several methods were performed, including inverse variance weighting (discovery data: odds ratio = 3.544, 95% confidence interval = 1.785-7.039, p = 0.000; replication data: odds ratio = 3.167, 95% confidence interval = 2.476-4.052, p = 0.000), MR-Egger (discovery data: odds ratio = 7.178, 95% confidence interval = 0.057-909.525, p = 0.429; replication data: odds ratio = 2.262, 95% confidence interval = 0.580-8.825, p = 0.246), weighted median (discovery data: odds ratio = 2.730, 95% confidence interval = 1.112-6.702, p = 0.028; replication data: odds ratio = 3.243, 95% confidence interval = 2.378-4.422, p = 0.000), MR-PRESSO (discovery data: odds ratio = 3.544, 95% confidence interval = 1.785-7.039, p = 0.001; replication data: odds ratio = 3.167, 95% confidence interval = 2.476-4.052, p = 0.000) methods. The results were consistent across these methods. The results obtained from discovery data are consistent with those obtained from discovery data. In the multivariable mendelian randomization, after adjusting for various covariates such as body mass index, current tobacco smoking, alcohol intake frequency, Total body bone mineral density, and vigorous physical activity, there is a consistent correlation between mood instability and chronic low back pain.ConclusionThis study provides robust evidence supporting a causal relationship between mood instability and the development of low back pain. Our findings suggest that addressing mood instability may play a crucial role in prevention and management strategies for individuals experiencing low back pain.

Project description:BackgroundSmoking was strongly associated with breast cancer in previous studies. Whether smoking promotes breast cancer through DNA methylation remains unknown.MethodsTwo-sample Mendelian randomization (MR) analyses were conducted to assess the causal effect of smoking-related DNA methylation on breast cancer risk. We used 436 smoking-related CpG sites extracted from 846 middle-aged women in the ARIES project as exposure data. We collected summary data of breast cancer from one of the largest meta-analyses, including 69,501 cases for ER+ breast cancer and 21,468 cases for ER- breast cancer. A total of 485 single-nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for smoking-related DNA methylation. We further performed an MR Steiger test to estimate the likely direction of causal estimate between DNA methylation and breast cancer. We also conducted colocalization analysis to evaluate whether smoking-related CpG sites shared a common genetic causal SNP with breast cancer in a given region.ResultsWe established four significant associations after multiple testing correction: the CpG sites of cg2583948 [OR = 0.94, 95% CI (0.91-0.97)], cg0760265 [OR = 1.07, 95% CI (1.03-1.11)], cg0420946 [OR = 0.95, 95% CI (0.93-0.98)], and cg2037583 [OR =1.09, 95% CI (1.04-1.15)] were associated with the risk of ER+ breast cancer. All the four smoking-related CpG sites had a larger variance than that in ER+ breast cancer (all p < 1.83 × 10-11) in the MR Steiger test. Further colocalization analysis showed that there was strong evidence (based on PPH4 > 0.8) supporting a common genetic causal SNP between the CpG site of cg2583948 [with IMP3 expression (PPH4 = 0.958)] and ER+ breast cancer. There were no causal associations between smoking-related DNA methylation and ER- breast cancer.ConclusionsThese findings highlight potential targets for the prevention of ER+ breast cancer. Tissue-specific epigenetic data are required to confirm these results.

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Smoking is associated with, but does not cause, depressed mood in pregnancy--a mendelian randomization study.

Publications

Smoking is associated with, but does not cause, depressed mood in pregnancy--a mendelian randomization study.

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