TYROBP genetic variants in early-onset Alzheimer's disease

We aimed to identify new candidate genes potentially involved in early-onset Alzheimer's disease (EOAD). Exome sequencing was conducted on 45 EOAD patients with either a family history of Alzheimer's disease (AD, <65 years) or an extremely early age at the onset (≤55 years) followed by multiple variant filtering according to different modes of inheritance. We identified 29 candidate genes potentially involved in EOAD, of which the gene TYROBP, previously implicated in AD, was selected for genetic and functional follow-up. Using 3 patient cohorts, we observed rare coding TYROBP variants in 9 out of 1110 EOAD patients, whereas no such variants were detected in 1826 controls (p = 0.0001), suggesting that at least some rare TYROBP variants might contribute to EOAD risk. Overexpression of the p.D50_L51ins14 TYROBP mutant led to a profound reduction of TREM2 expression, a well-established risk factor for AD. This is the first study supporting a role for genetic variation in TYROBP in EOAD, with in vitro support for a functional effect of the p.D50_L51ins14 TYROBP mutation on TREM2 expression

Comparative Analyses of Stressors Experienced by Rural Low-Income Pregnant Women Experiencing Intimate Partner Violence and Those Who Are Not

OBJECTIVE: To describe the daily lives of rural pregnant women who smoked during pregnancy, with a focus on their sources of stress and the compounding effects of intimate partner violence (IPV). DESIGN: A qualitative study using content analysis of research nurse’s telephone logs from a large smoking cessation randomized controlled trial (N = 695) in which 33% of the sample (n = 227) experienced IPV in the past year. PARTICIPANTS: Fifty pregnant women, 25 who had experienced IPV in the past year and 25 who had never experienced IPV, were randomly selected from those who received a nurse-delivered telephone intervention for smoking cessation (n = 345). The mean age of the sample was 22 years, and the majority were White and living in a married-like relationship. RESULTS: Women experiencing IPV discussed certain stressors significantly more often than non-abused women. These stressors included finances, lack of social support, legal issues, transportation issues, and abuse by the intimate partner and others. CONCLUSION: Health care providers need to recognize that intimate partner violence creates a stress which can compound the stressors of pregnancy and poverty in rural areas. Offering these women a chance to talk about their lives can help them not only to locate necessary resources, but also to break down the barriers of isolation

Comparative Analyses of Stressors Experienced by Rural Low-Income Pregnant Women Experiencing Intimate Partner Violence and Those Who Are Not

OBJECTIVE: To describe the daily lives of rural pregnant women who smoked during pregnancy, with a focus on their sources of stress and the compounding effects of intimate partner violence (IPV). DESIGN: A qualitative study using content analysis of research nurse’s telephone logs from a large smoking cessation randomized controlled trial (N = 695) in which 33% of the sample (n = 227) experienced IPV in the past year. PARTICIPANTS: Fifty pregnant women, 25 who had experienced IPV in the past year and 25 who had never experienced IPV, were randomly selected from those who received a nurse-delivered telephone intervention for smoking cessation (n = 345). The mean age of the sample was 22 years, and the majority were White and living in a married-like relationship. RESULTS: Women experiencing IPV discussed certain stressors significantly more often than non-abused women. These stressors included finances, lack of social support, legal issues, transportation issues, and abuse by the intimate partner and others. CONCLUSION: Health care providers need to recognize that intimate partner violence creates a stress which can compound the stressors of pregnancy and poverty in rural areas. Offering these women a chance to talk about their lives can help them not only to locate necessary resources, but also to break down the barriers of isolation