Mental health problems disproportionately affect women, particularly during childbearing years. We sought to estimate the prevalence of antepartum mental health problems and determine potential risk factors in a representative USA population. We examined data on 3,051 pregnant women from 11 panels of the 1996-2006 Medical Expenditure Panel Survey. Poor antepartum mental health was defined by self report of mental health conditions or symptoms or a mental health rating of "fair" or "poor." Multivariate regression analyses modeled the odds of poor antepartum mental health; 7.8% of women reported poor antepartum mental health. A history of mental health problems increased the odds of poor antepartum mental health by a factor of 8.45 (95% CI, 6.01-11.88). Multivariate analyses were stratified by history of mental health problems. Significant factors among both groups included never being married and self-reported fair/poor health status. This study identifies key risk factors associated with antepartum mental health problems in a nationally representative sample of pregnant women. Women with low social support, in poor health, or with a history of poor mental health are at an increased risk of having antepartum mental health problems. Understanding these risk factors is critical to improve the long-term health of women and their children.

Study objectives

Periodic limb movement in sleep is a common sleep phenotype characterized by repetitive leg movements that occur during or before sleep. We conducted a genome-wide association study (GWAS) of periodic limb movements in sleep (PLMS) using a joint analysis (i.e., discovery, replication, and joint meta-analysis) of four cohorts (MrOS, the Wisconsin Sleep Cohort Study, HypnoLaus, and MESA), comprised of 6843 total subjects.

Methods

The MrOS study and Wisconsin Sleep Cohort Study (N = 1745 cases) were used for discovery. Replication in the HypnoLaus and MESA cohorts (1002 cases) preceded joint meta-analysis. We also performed LD score regression, estimated heritability, and computed genetic correlations between potentially associated traits such as restless leg syndrome (RLS) and insomnia. The causality and direction of the relationships between PLMS and RLS was evaluated using Mendelian randomization.

Results

We found 2 independent loci were significantly associated with PLMS: rs113851554 (p = 3.51 × 10-12, β = 0.486), an SNP located in a putative regulatory element of intron eight of MEIS1 (2p14); and rs9369062 (p = 3.06 × 10-22, β = 0.2093), a SNP located in the intron region of BTBD9 (6p12); both of which were also lead signals in RLS GWAS. PLMS is genetically correlated with insomnia, risk of stroke, and RLS, but not with iron deficiency. Pleiotropy adjusted Mendelian randomization analysis identified a causal effect of RLS on PLMS.

Conclusions

Because PLMS is more common than RLS, PLMS may have multiple causes and additional studies are needed to further validate these findings.

Obstructive sleep apnea (OSA) is a common heritable disorder displaying marked sexual dimorphism in disease prevalence and progression. Previous genetic association studies have identified a few genetic loci associated with OSA and related quantitative traits, but they have only focused on single ethnic groups, and a large proportion of the heritability remains unexplained. The apnea-hypopnea index (AHI) is a commonly used quantitative measure characterizing OSA severity. Because OSA differs by sex, and the pathophysiology of obstructive events differ in rapid eye movement (REM) and non-REM (NREM) sleep, we hypothesized that additional genetic association signals would be identified by analyzing the NREM/REM-specific AHI and by conducting sex-specific analyses in multiethnic samples. We performed genome-wide association tests for up to 19,733 participants of African, Asian, European, and Hispanic/Latino American ancestry in 7 studies. We identified rs12936587 on chromosome 17 as a possible quantitative trait locus for NREM AHI in men (N = 6,737; P = 1.7 × 10^-8) but not in women (P = 0.77). The association with NREM AHI was replicated in a physiological research study (N = 67; P = 0.047). This locus overlapping the RAI1 gene and encompassing genes PEMT1, SREBF1, and RASD1 was previously reported to be associated with coronary artery disease, lipid metabolism, and implicated in Potocki-Lupski syndrome and Smith-Magenis syndrome, which are characterized by abnormal sleep phenotypes. We also identified gene-by-sex interactions in suggestive association regions, suggesting that genetic variants for AHI appear to vary by sex, consistent with the clinical observations of strong sexual dimorphism.