Obesity and type 2 diabetes (T2D) occur disproportionately among African-American (AA) women. The neuroendocrine system, and in particular the hypothalamic-pituitary-adrenal (HPA) axis, plays a key role in the homeostasis of body weight through regulation of energy intake and expenditure. Perinatal events may cause changes in leptin and insulin levels that lead to altered hypothalamic development and lasting effects on body weight regulation and glucose homeostasis. Chronic stressors can cause deregulation of both the HPA axis and the sympathetic adrenal medullary axis, increasing the risk of developing metabolic diseases such as obesity and T2D. Relative to U.S. white women, AA women have a higher exposure to factors that can unfavorably alter functioning of the neuroendocrine system. Specifically, AA women are less likely to have been breastfed, more likely to have been born preterm and with a low birth weight, and more likely to experience violence victimization, racism, depression, and sleep deprivation. Because the FTO gene, the gene most strongly associated with fat mass and obesity in AA as well as European ancestry populations, is highly expressed in the central nervous system and hypothalamus and is involved in food intake regulation, genetic variants of the FTO gene may characterize individuals who are more susceptible to obesity or T2D under conditions that affect neuroendocrine functioning. We propose to prospectively assess whether the above- mentioned factors are associated with weight gain and incidence of T2D in AA women, and whether genetic variants in the FTO gene modify these associations. Our study will be based on the Black Women's Health Study (BWHS), an ongoing cohort study of 59,000 AA women with a wealth of prospectively collected data and with stored DNA samples. The BWHS has collected information on weight every two years during follow-up since baseline in 1995, and over 6,000 incident cases of T2D have occurred through 2009. We have already published on the relation of body mass index, dietary factors, and physical activity to risk of T2D and have also reported positive associations of racism and low socioeconomic status with weight gain in the BWHS. The proposed study will provide novel data on factors that may be contributing to the epidemic of obesity and T2D in AA women and in other population groups as well.
African American (AA) women are disproportionately affected by obesity and type 2 diabetes (T2D), with a heavy burden of associated health problems. The proposed study will provide data on whether psychosocial stressors and other factors that unfavorably alter the neuroendocrine system, which is involved in regulation of body weight, contribute to increased weight gain and T2D incidence in AA women.
|Uribe-Salazar, José M; Palmer, Julie R; Haddad, Stephen A et al. (2018) Admixture mapping and fine-mapping of type 2 diabetes susceptibility loci in African American women. J Hum Genet 63:1109-1117|
|Ochs-Balcom, Heather M; Shaw, Holly; Preus, Leah et al. (2018) Admixture mapping and fine-mapping of birth weight loci in the Black Women's Health Study. Hum Genet :|
|Bacon, Kathryn L; Stuver, Sherri O; Cozier, Yvette C et al. (2017) Perceived racism and incident diabetes in the Black Women's Health Study. Diabetologia 60:2221-2225|
|Haddad, Stephen A; Palmer, Julie R; Lunetta, Kathryn L et al. (2017) A novel TCF7L2 type 2 diabetes SNP identified from fine mapping in African American women. PLoS One 12:e0172577|
|Ruiz-Narváez, Edward A; Haddad, Stephen A; Rosenberg, Lynn et al. (2016) Birth weight modifies the association between central nervous system gene variation and adult body mass index. J Hum Genet 61:193-8|
|Vimalananda, Varsha G; Palmer, Julie R; Gerlovin, Hanna et al. (2015) Night-shift work and incident diabetes among African-American women. Diabetologia 58:699-706|
|Ruiz-Narváez, Edward A; Palmer, Julie R; Gerlovin, Hanna et al. (2014) Birth weight and risk of type 2 diabetes in the black women's health study: does adult BMI play a mediating role? Diabetes Care 37:2572-8|
|Vimalananda, Varsha G; Palmer, Julie R; Gerlovin, Hanna et al. (2014) Depressive symptoms, antidepressant use, and the incidence of diabetes in the Black Women's Health Study. Diabetes Care 37:2211-7|
|Ruiz-Narváez, Edward A (2014) Redundant enhancers and causal variants in the TCF7L2 gene. Eur J Hum Genet 22:1243-6|
|Ruiz-Narváez, Edward A (2014) Hypothesis about alternative use of redundant regulatory elements was validated by recent results. Med Hypotheses 83:513-4|