Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe)

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study. Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value<2×$10^{−6}$. Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts. Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

Federalism unmasked [electronic resource]: or The rights of the states, the congress, the executive, and the people, vindicated against the encroachments of the judiciary, prompted by the modern apostate democracy. Being a compilation from the writings and speeches of the leaders of the old Jeffersonian Republican party./

Caption title.Electronic text and image data.Mode of access: Internet

Federalism unmasked: or The rights of the states, the congress, the executive, and the people, vindicated against the encroachments of the judiciary, prompted by the modern apostate democracy. Being a compilation from the writings and speeches of the leaders of the old Jeffersonian Republican party./ By Daniel R. Goodloe.

15 p ; 23 cm.Caption title.Electronic text and image data. Ann Arbor, Mich. : University of Michigan, Digital Library Initiatives, 1996. Includes both TIFF files and keyword searchable text. [Making of America] This volume is made possible by a grant from the Andrew W. Mellon Foundation

Voices From the Hilo Women\u27s Health Study: Talking Story About Menopause

Our purpose in conducting this qualitative study was to examine how a multiethnic sample of women living in Hilo, Hawai’i, describe menopause. Interviews were conducted with 185 pre-, peri-, and post-menopausal women aged 45 to 55. We found that pre-menopausal women felt anxious compared with peri- and post-menopausal women\u27s more affirmative attitudes of increasing confidence and freedom in this new cycle of life. A dominant theme was the construction of a post-menstrual identity. Peri-and post-menopausal women\u27s attitudes were not biomedically oriented. Local culture and the island lifestyle may provide a positive atmosphere for women going through menopause

Diurnal rhythm and concordance between objective and subjective hot flashes: the Hilo Women\u27s Health Study

Objective To test for a diurnal pattern in hot flashes in a multi-ethnic population living in a hot, humid environment. To examine rates of concordance between objective and subjective measures of hot flashes using ambulatory and laboratory measures. Methods Study participants aged 45–55 were recruited from the general population of Hilo, Hawaii. Women wore a Biolog hot flash monitor, kept a diary for 24-hours, and also participated in 3-hour laboratory measures (n=199). Diurnal patterns were assessed using polynomial regression. For each woman, objectively recorded hot flashes that matched subjective experience were treated as true positive readings. Subjective hot flashes were considered the standard for computing false positive and false negative readings. True positive, false positive, and false negative readings were compared across ethnic groups by chi-square analyses. Results Frequencies of sternal, nuchal and subjective hot flashes peaked at 15:00 ± 1 hour with no difference by ethnicity. Laboratory results supported the pattern seen in ambulatory monitoring. Sternal and nuchal monitoring showed the same frequency of true positive measures, but non-sternal electrodes picked up more false positive readings. Laboratory monitoring showed very low frequencies of false negatives. There were no ethnic differences in the frequency of true positive or false positive measures. Women of European descent were more likely to report hot flashes that were not objectively demonstrated (false negative measures). Conclusions The diurnal pattern and peak in hot flash occurrence in the hot humid environment of Hilo was similar to results from more temperate environments. Lack of variation in sternal vs. non-sternal measures, and in true positive measures across ethnicities suggests no appreciable effect of population variation in sweating patterns

Midfoot and Hindfoot Charcot Deformity Correction is Well Maintained with Beam Fixation

Category: Midfoot/Forefoot; Diabetes Introduction/Purpose: Charcot arthropathy is a neurotraumatic foot disorder seen in patients with peripheral neuropathy. Surgical reconstruction via medial column arthrodesis with beams can restore plantigrade foot anatomy with decreased soft tissue dissection and improved bony compression. Methods: We identified 12 patients with midfoot (n=7) or hindfoot (n=5) Charcot who underwent medial column beaming arthrodesis between 2015 and 2021 b y one of two fellowship-trained foot and ankle surgeons at an academic medical center. Data collected from patient charts included demographics, medical history, complications, and reoperation rate. Meary’s angle was measured on lateral weightbearing radiographs preoperatively and up to two years postoperatively. Mean follow-up time was 2.50 (range, 1.04-6.98) years. Statistical analysis included correlation, two-tailed Student t-test, and Chi-squared test. Results: Meary’s angle was recorded preoperatively for 12 patients (19.3° ± 6.7°) and postoperatively at three months for 12 patients (4.0° ± 6.7°), at six months for 12 patients (7.1° ± 9.7°), at one year for 11 patients (6.1° ± 9.4°), and at two years for five patients (10.2° ± 6.4°). However, two (16.7%) patients showed a loss of deformity correction, which was demonstrated by a Meary’s angle that was greater at final follow-up than preoperatively. Overall complication, infection, reoperation rates were 50.0%, 41.7%, and 58.3%, respectively. Finally, dependent on preoperative ulceration, those with and without an ulcer did not differ in Meary’s angle at any time point, overall complication, infection, nor reoperation rate. Conclusion: Although the results showed a relatively high complication rate, the use of beaming arthrodesis was generally able to maintain a plantigrade foot and overall alignment, while decreasing the recurrence of plantar ulceration

Association of Genetic Loci with Sleep Apnea in European Americans and African-Americans: The Candidate Gene Association Resource (CARe)

Although obstructive sleep apnea (OSA) is known to have a strong familial basis, no genetic polymorphisms influencing apnea risk have been identified in cross-cohort analyses. We utilized the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe) to identify sleep apnea susceptibility loci. Using a panel of 46,449 polymorphisms from roughly 2,100 candidate genes on a customized Illumina iSelect chip, we tested for association with the apnea hypopnea index (AHI) as well as moderate to severe OSA (AHI≥15) in 3,551 participants of the Cleveland Family Study and two cohorts participating in the Sleep Heart Health Study.Among 647 African-Americans, rs11126184 in the pleckstrin (PLEK) gene was associated with OSA while rs7030789 in the lysophosphatidic acid receptor 1 (LPAR1) gene was associated with AHI using a chip-wide significance threshold of p-value−6. Among 2,904 individuals of European ancestry, rs1409986 in the prostaglandin E2 receptor (PTGER3) gene was significantly associated with OSA. Consistency of effects between rs7030789 and rs1409986 in LPAR1 and PTGER3 and apnea phenotypes were observed in independent clinic-based cohorts.Novel genetic loci for apnea phenotypes were identified through the use of customized gene chips and meta-analyses of cohort data with replication in clinic-based samples. The identified SNPs all lie in genes associated with inflammation suggesting inflammation may play a role in OSA pathogenesis.</p