Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using $\sim$2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant $(p<5 \times 10^{-8})$ or suggestive associations $(p<4 \times 10^{-7})$ were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding $(p<4 \times 10^{-7})$. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels

Psychometric characteristics of the Spanish version of instruments to measure neck pain disability

Background: The NDI, COM and NPQ are evaluation instruments for disability due to NP. There was no Spanish version of NDI or COM for which psychometric characteristics were known. The objectives of this study were to translate and culturally adapt the Spanish version of the Neck Disability Index Questionnaire (NDI), and the Core Outcome Measure (COM), to validate its use in Spanish speaking patients with non-specific neck pain (NP), and to compare their psychometric characteristics with those of the Spanish version of the Northwick Pain Questionnaire (NPQ). Methods: Translation/re-translation of the English versions of the NDI and the COM was done blindly and independently by a multidisciplinary team. The study was done in 9 primary care Centers and 12 specialty services from 9 regions in Spain, with 221 acute, subacute and chronic patients who visited their physician for NP: 54 in the pilot phase and 167 in the validation phase. Neck pain (VAS), referred pain (VAS), disability (NDI, COM and NPQ), catastrophizing (CSQ) and quality of life (SF-12) were measured on their first visit and 14 days later. Patients' self-assessment was used as the external criterion for pain and disability. In the pilot phase, patients' understanding of each item in the NDI and COM was assessed, and on day 1 test-retest reliability was estimated by giving a second NDI and COM in which the name of the questionnaires and the order of the items had been changed. Results: Comprehensibility of NDI and COM were good. Minutes needed to fill out the questionnaires [median, (P25, P75)]: NDI. 4 (2.2, 10.0), COM: 2.1 (1.0, 4.9). Reliability: [ICC, (95%CI)]: NDI: 0.88 (0.80, 0.93). COM: 0.85 (0.75,0.91). Sensitivity to change: Effect size for patients having worsened, not changed and improved between days 1 and 15, according to the external criterion for disability: NDI: -0.24, 0.15, 0.66; NPQ: -0.14, 0.06, 0.67; COM: 0.05, 0.19, 0.92. Validity: Results of NDI, NPQ and COM were consistent with the external criterion for disability, whereas only those from NDI were consistent with the one for pain. Correlations with VAS, CSQ and SF-12 were similar for NDI and NPQ (absolute values between 0.36 and 0.50 on day 1, between 0.38 and 0.70 on day 15), and slightly lower for COM (between 0.36 and 0.48 on day 1, and between 0.33 and 0.61 on day 15). Correlation between NDI and NPQ: r = 0.84 on day 1, r = 0.91 on day 15. Correlation between COM and NPQ: r = 0.63 on day 1, r = 0.71 on day 15. Conclusion: Although most psychometric characteristics of NDI, NPQ and COM are similar, those from the latter one are worse and its use may lead to patients' evolution seeming more positive than it actually is. NDI seems to be the best instrument for measuring NP-related disability, since its results are the most consistent with patient's assessment of their own clinical status and evolution. It takes two more minutes to answer the NDI than to answer the COM, but it can be reliably filled out by the patient without assistance

Genome-Wide Association Studies of Serum Magnesium, Potassium, and Sodium Concentrations Identify Six Loci Influencing Serum Magnesium Levels

Magnesium, potassium, and sodium, cations commonly measured in serum, are involved in many physiological processes including energy metabolism, nerve and muscle function, signal transduction, and fluid and blood pressure regulation. To evaluate the contribution of common genetic variation to normal physiologic variation in serum concentrations of these cations, we conducted genome-wide association studies of serum magnesium, potassium, and sodium concentrations using ∼2.5 million genotyped and imputed common single nucleotide polymorphisms (SNPs) in 15,366 participants of European descent from the international CHARGE Consortium. Study-specific results were combined using fixed-effects inverse-variance weighted meta-analysis. SNPs demonstrating genome-wide significant (p<5×10−8) or suggestive associations (p<4×10−7) were evaluated for replication in an additional 8,463 subjects of European descent. The association of common variants at six genomic regions (in or near MUC1, ATP2B1, DCDC5, TRPM6, SHROOM3, and MDS1) with serum magnesium levels was genome-wide significant when meta-analyzed with the replication dataset. All initially significant SNPs from the CHARGE Consortium showed nominal association with clinically defined hypomagnesemia, two showed association with kidney function, two with bone mineral density, and one of these also associated with fasting glucose levels. Common variants in CNNM2, a magnesium transporter studied only in model systems to date, as well as in CNNM3 and CNNM4, were also associated with magnesium concentrations in this study. We observed no associations with serum sodium or potassium levels exceeding p<4×10−7. Follow-up studies of newly implicated genomic loci may provide additional insights into the regulation and homeostasis of human serum magnesium levels

2018 Research & Innovation Day Program

A one day showcase of applied research, social innovation, scholarship projects and activities.https://first.fanshawec.ca/cri_cripublications/1005/thumbnail.jp

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

Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure.

Numerous genetic loci have been associated with systolic blood pressure (SBP) and diastolic blood pressure (DBP) in Europeans. We now report genome-wide association studies of pulse pressure (PP) and mean arterial pressure (MAP). In discovery (N = 74,064) and follow-up studies (N = 48,607), we identified at genome-wide significance (P = 2.7 × 10(-8) to P = 2.3 × 10(-13)) four new PP loci (at 4q12 near CHIC2, 7q22.3 near PIK3CG, 8q24.12 in NOV and 11q24.3 near ADAMTS8), two new MAP loci (3p21.31 in MAP4 and 10q25.3 near ADRB1) and one locus associated with both of these traits (2q24.3 near FIGN) that has also recently been associated with SBP in east Asians. For three of the new PP loci, the estimated effect for SBP was opposite of that for DBP, in contrast to the majority of common SBP- and DBP-associated variants, which show concordant effects on both traits. These findings suggest new genetic pathways underlying blood pressure variation, some of which may differentially influence SBP and DBP

Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or  ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention

TESTING VIRGINITY: HIV/AIDS, MODERNITY &amp; ETHNICITY IN POST-APARTHEID SOUTH AFRICA

TESTING VIRGINITY: HIV/AIDS, MODERNITY &amp; ETHNICITY IN POST-APARTHEID SOUTH AFRICA TESTING VIRGINITY: HIV/AIDS, MODERNITY &amp; ETHNICITY IN POST-APARTHEID SOUTH AFRICAAt the heart of this thesis is an examination of virginity testing as a practice steeped in tradition and born anew to fight the scourge of HIV/AIDS among the Zulu in South Africa. Virginity testing as an HIV/AIDS education and prevention program contrasts with the nationally-supported and internationally-funded loveLife program which acknowledges sexual activity among youth and tries to build their individual commitment to increasing their life opportunities. I argue that both the provocative loveLife campaign and the cultural revival of virginity testing are modern productions with particular histories and social trajectories. The modern practice of virginity testing, while not effective as a bio-medical intervention in HIV/AIDS education and prevention, finds it success in ethnic revitalization. I trace the changing understandings and embodiments of Zulu ethnicity as the political economy of South Africa changed. Paying special attention to the value placed on the story of King Shaka from the colonial time to the present, I submit that Zulu was represented through bellicose masculine images in the early colonial period and in the extractive capitalist system, Zulu ethnic identity was mobilized for worker solidarity; under apartheid, Zulu was a language of community and a political boundary. In the post-apartheid moment, the Zulu king, represents the Zulu ethnic group. Virginity testing and the associated Reed Dance and the ritual for the rain goddess Nomkhubulwane contribute to the legitimation of the Zulu king as representative of the group. I argue that the Reed Dance takes cues from the Ncwala (ritual of kingship) and the umchwaso (a chastity rite for unmarried girls) of the closely related Swazi monarchy and that the Reed Dance is one of the few public instantiations of kingship in modern Zululand. The young women who participate in the Reed Dance must have passed a virginity test. In the absence of the former powers of Zulu kings, the present king marks his dominion over young women's bodies. One chapter is devoted to women's responses to the King's edict that women should cover their nude bodies in the Reed Dance ceremony. This deviation from tradition tests the King's authority and gives evidence of the sense of pride and pleasure that young women derive from their participation in the ceremony.This dissertation also shows the agency of women engaged in virginity testing, as organizers, testers, and participants. Virginity testing is the not the first time that Zulu women have organized to counter what they saw as the deleterious effects of industrial capitalism and migrant labor on family life and authority over children. I investigate the Bantu Purity League and the Women's Wing of the Inkatha Yenkhululeku Yesizwe as precursors to the present virginity testing movement. In all these instances, women believe that their welfare could be best secured through a re-affirmation of values that include patriarchal power. In a sense, they take power in their own hands to ensure the survival of the family and male authority. Another instance that underscores women's sense of their own agency in the virginity testing movement is their opposition to the Children's Rights Bill introduced to South Africa in 2005. Virginity testing advocates saw this Bill as eroding cultural practices and actively campaigned against it.The virginity testing movement is not monolithic. This study is indebted to the openness of the virginity tester Nomagugu Ngobese, who created the modern Nomkhubulwane ceremony, which requires that girls be virgins to participate, and who trained a large number of virginity testers. I also interview testers from different backgrounds and who employ a range of approaches to the incorporation of information on sexuality into their virginity testing programs. When virginity testers look for signs of virginity, they look for more than an intact hymen. They note firmness and ... of other body parts and are concerned with the general posture and conduct of the young women who undergo testing. The young women who participate in virginity testing come from a wide range of backgrounds and not all of them maintain their virginity. Most participate for the sense of camaraderie and to learn about and show respect for Zulu customs. I hope to widen analytical discussions on the structural factors that should be considered in HIV/AIDS education and prevention policies to include culture, custom, and ethnicity. Based on 15 months of fieldwork, I argue that the convergence of a growing sense of individuality, freedom of choice and human rights introduced by democracy and the simultaneous decrease in political and economic opportunity promised with democracy facilitated the re-emergence and appeal of traditional practice and conservative values. Virginity testing is a significant cultural institution that has tremendous potential to intercede in a host of developmental areas that are of importance to women and girls and the goals of human rights institutions and AIDS policy developers. Further, attending to the workings of history and the myriad ways individuals engage the contested terrains of culture, gender and rights can serve as a counter point to the decontextualized understandings of gender and culture that dominate many HIV/AIDS and gender interventions

TESTING VIRGINITY: HIV/AIDS, MODERNITY &amp; ETHNICITY IN POST-APARTHEID SOUTH AFRICA

TESTING VIRGINITY: HIV/AIDS, MODERNITY &amp; ETHNICITY IN POST-APARTHEID SOUTH AFRICA TESTING VIRGINITY: HIV/AIDS, MODERNITY &amp; ETHNICITY IN POST-APARTHEID SOUTH AFRICAAt the heart of this thesis is an examination of virginity testing as a practice steeped in tradition and born anew to fight the scourge of HIV/AIDS among the Zulu in South Africa. Virginity testing as an HIV/AIDS education and prevention program contrasts with the nationally-supported and internationally-funded loveLife program which acknowledges sexual activity among youth and tries to build their individual commitment to increasing their life opportunities. I argue that both the provocative loveLife campaign and the cultural revival of virginity testing are modern productions with particular histories and social trajectories. The modern practice of virginity testing, while not effective as a bio-medical intervention in HIV/AIDS education and prevention, finds it success in ethnic revitalization. I trace the changing understandings and embodiments of Zulu ethnicity as the political economy of South Africa changed. Paying special attention to the value placed on the story of King Shaka from the colonial time to the present, I submit that Zulu was represented through bellicose masculine images in the early colonial period and in the extractive capitalist system, Zulu ethnic identity was mobilized for worker solidarity; under apartheid, Zulu was a language of community and a political boundary. In the post-apartheid moment, the Zulu king, represents the Zulu ethnic group. Virginity testing and the associated Reed Dance and the ritual for the rain goddess Nomkhubulwane contribute to the legitimation of the Zulu king as representative of the group. I argue that the Reed Dance takes cues from the Ncwala (ritual of kingship) and the umchwaso (a chastity rite for unmarried girls) of the closely related Swazi monarchy and that the Reed Dance is one of the few public instantiations of kingship in modern Zululand. The young women who participate in the Reed Dance must have passed a virginity test. In the absence of the former powers of Zulu kings, the present king marks his dominion over young women's bodies. One chapter is devoted to women's responses to the King's edict that women should cover their nude bodies in the Reed Dance ceremony. This deviation from tradition tests the King's authority and gives evidence of the sense of pride and pleasure that young women derive from their participation in the ceremony.This dissertation also shows the agency of women engaged in virginity testing, as organizers, testers, and participants. Virginity testing is the not the first time that Zulu women have organized to counter what they saw as the deleterious effects of industrial capitalism and migrant labor on family life and authority over children. I investigate the Bantu Purity League and the Women's Wing of the Inkatha Yenkhululeku Yesizwe as precursors to the present virginity testing movement. In all these instances, women believe that their welfare could be best secured through a re-affirmation of values that include patriarchal power. In a sense, they take power in their own hands to ensure the survival of the family and male authority. Another instance that underscores women's sense of their own agency in the virginity testing movement is their opposition to the Children's Rights Bill introduced to South Africa in 2005. Virginity testing advocates saw this Bill as eroding cultural practices and actively campaigned against it.The virginity testing movement is not monolithic. This study is indebted to the openness of the virginity tester Nomagugu Ngobese, who created the modern Nomkhubulwane ceremony, which requires that girls be virgins to participate, and who trained a large number of virginity testers. I also interview testers from different backgrounds and who employ a range of approaches to the incorporation of information on sexuality into their virginity testing programs. When virginity testers look for signs of virginity, they look for more than an intact hymen. They note firmness and ... of other body parts and are concerned with the general posture and conduct of the young women who undergo testing. The young women who participate in virginity testing come from a wide range of backgrounds and not all of them maintain their virginity. Most participate for the sense of camaraderie and to learn about and show respect for Zulu customs. I hope to widen analytical discussions on the structural factors that should be considered in HIV/AIDS education and prevention policies to include culture, custom, and ethnicity. Based on 15 months of fieldwork, I argue that the convergence of a growing sense of individuality, freedom of choice and human rights introduced by democracy and the simultaneous decrease in political and economic opportunity promised with democracy facilitated the re-emergence and appeal of traditional practice and conservative values. Virginity testing is a significant cultural institution that has tremendous potential to intercede in a host of developmental areas that are of importance to women and girls and the goals of human rights institutions and AIDS policy developers. Further, attending to the workings of history and the myriad ways individuals engage the contested terrains of culture, gender and rights can serve as a counter point to the decontextualized understandings of gender and culture that dominate many HIV/AIDS and gender interventions

Long-Term Evolution of Composition and Structure after Repeated Group Selection Over Eight Decades

: In northeastern North America, group selection is frequently used in northern hardwood forests to maintain uneven-aged stand structure and promote regeneration of tree species spanning a range of shade tolerances. For this study, long-term application of group selection at the Bartlett Experimental Forest, New Hampshire, USA provided a unique opportunity to address cohort and stand level progression after 80-years of treatment. Cohort-level evolution reflected successional and developmental dynamics associated with even-aged forest systems, whereas aggregate, stand-level conditions were consistent with expectations for uneven-aged systems. As cohorts aged, diameter distributions progressed towards descending monotonic forms and species composition transitioned from shade-intolerant species to shade-tolerant species. Standing deadwood and downed woody material in cohorts followed trajectories of aging even-aged stands through time. Although American beech (Fagus grandifolia Ehrh.) was a primary species across cohorts and at the stand level, stand level regeneration included a mixture of ecologically and commercially valuable species. These long-term results offer important insights into emergent cohort and stand-level conditions and processes that may affect continued recruitment of desirable compositional and structural conditions in stands managed using group selection over numerous cutting cycles.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author