A candidate gene analysis and GWAS for genes associated with maternal nondisjunction of chromosome 21

Human nondisjunction errors in oocytes are the leading cause of pregnancy loss, and for pregnancies that continue to term, the leading cause of intellectual disabilities and birth defects. For the first time, we have conducted a candidate gene and genome-wide association study to identify genes associated with maternal nondisjunction of chromosome 21 as a first step to understand predisposing factors. A total of 2,186 study participants were genotyped on the HumanOmniExpressExome-8v1-2 array. These participants included 749 live birth offspring with standard trisomy 21 and 1,437 parents. Genotypes from the parents and child were then used to identify mothers with nondisjunction errors derived in the oocyte and to establish the type of error (meiosis I or meiosis II). We performed a unique set of subgroup comparisons designed to leverage our previous work suggesting that the etiologies of meiosis I and meiosis II nondisjunction differ for trisomy 21. For the candidate gene analysis, we selected genes associated with chromosome dynamics early in meiosis and genes associated with human global recombination counts. Several candidate genes showed strong associations with maternal nondisjunction of chromosome 21, demonstrating that genetic variants associated with normal variation in meiotic processes can be risk factors for nondisjunction. The genome-wide analysis also suggested several new potentially associated loci, although follow-up studies using independent samples are required

A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain

Background. Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. Methods. A genome-wide association study (GWAS; ) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Results. Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; for all) near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. Conclusions. Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain

ПОЖИЛОЙ ВОЗРАСТ, ЗАПОР И ДЕПРЕССИЯ: КАК ЛЕЧИТЬ?

Constipation is one of the key problems of modern therapy for elderly people. The research aim was to study the features of the psychological and microbiological status of the advanced and senile age patients with functional constipation and to see the effect of educational programmes on compliance of the patients with the therapy in the out!patient departments. The investigation showed that depression was more frequent in the patients of group 1 (68.4 % of the cases) with compensated function of the large gut whereas in the 2nd group – 34.6 % (compensated) and in the 3rd group – 41.5 % (subcompensated)cases. The 3rd degree dysbiosis was found in all patoents irrespective of the extern of disorder of the motor!kinetic function in the large gut.Запор является одной из ключевых проблем современной терапии в пожилом возрасте. Целью исследования явилось изучение особенностей психологического и микробиологического статусов у пациентов пожилого и старческого возраста с функциональным запором, а также влияние образовательных программ на приверженность к терапии в амбулаторных условиях. Как показали результаты исследования, чаще всего депрессия встречалась у пациентов 1 группы - в 68,4 % случаев - с компенсированной функцией толстой кишки, тогда как во 2 группе - в 34,6 % (компенсированная) и 3 группе - в 41,5 % (субкомпенсированная) случаев. Независимо от степени нарушения моторно-кинетической функции толстой кишки, у всех пациентов выявлялась 3-я степень дисбиоза. Проведение обучающих программ, дающих знание о физиологических особенностях толстой кишки, оказывало положительное влияние на приверженность пациентов к соматической и фармакопсихологической терапии

A Preliminary Genome-Wide Association Study of Pain-Related Fear: Implications for Orofacial Pain

Background. Acute and chronic orofacial pain can significantly impact overall health and functioning. Associations between fear of pain and the experience of orofacial pain are well-documented, and environmental, behavioral, and cognitive components of fear of pain have been elucidated. Little is known, however, regarding the specific genes contributing to fear of pain. Methods. A genome-wide association study (GWAS; N=990) was performed to identify plausible genes that may predispose individuals to various levels of fear of pain. The total score and three subscales (fear of minor, severe, and medical/dental pain) of the Fear of Pain Questionnaire-9 (FPQ-9) were modeled in a variance components modeling framework to test for genetic association with 8.5 M genetic variants across the genome, while adjusting for sex, age, education, and income. Results. Three genetic loci were significantly associated with fear of minor pain (8q24.13, 8p21.2, and 6q26; p<5×10-8 for all) near the genes TMEM65, NEFM, NEFL, AGPAT4, and PARK2. Other suggestive loci were found for the fear of pain total score and each of the FPQ-9 subscales. Conclusions. Multiple genes were identified as possible candidates contributing to fear of pain. The findings may have implications for understanding and treating chronic orofacial pain

Limb development genes underlie variation in human fingerprint patterns

Fingerprints are of long-standing practical and cultural interest, but little is known about the mechanisms that underlie their variation. Using genome-wide scans in Han Chinese cohorts, we identified 18 loci associated with fingerprint type across the digits, including a genetic basis for the long-recognized “pattern-block” correlations among the middle three digits. In particular, we identified a variant near EVI1 that alters regulatory activity and established a role for EVI1 in dermatoglyph patterning in mice. Dynamic EVI1 expression during human development supports its role in shaping the limbs and digits, rather than influencing skin patterning directly. Trans-ethnic meta-analysis identified 43 fingerprint-associated loci, with nearby genes being strongly enriched for general limb development pathways. We also found that fingerprint patterns were genetically correlated with hand proportions. Taken together, these findings support the key role of limb development genes in influencing the outcome of fingerprint patterning

Rebirth, devastation and sickness: analyzing the role of metaphor in media discourses of nuclear power

International audienceNuclear power plays an important but controversial role in policies to ensure domestic energy security, fuel poverty reduction and the mitigation of climate change. Our article construes the problem of nuclear power in terms of social discourse, language and public choice; specifically examining the role that metaphors play in the policy domain. We empirically analyze metaphors as framing devices in nuclear energy policy debates in the UK between April 2009 and March 2013, thereby capturing the impact of the Fukushima nuclear disaster in 2011. We employ documentary analysis of major UK national broadsheet and tabloid newspapers, using electronic bibliographic tools to extract the metaphors. We then map these metaphors using a Type Hierarchy Analysis, which examines how elements of the target domain (energy technologies and policies) originate from a different source domain. Type hierarchies identify and categorize metaphors, defining the affectual and emotional responses associated with them, providing us with grounded insight into their role in shaping discourse and as a consequence influence public engagement with energy policy. Our analysis highlights three emergent domains of discourse metaphors and discusses the implications of their deployment. Metaphors were found to be classified into three different categories: Rebirth (Renaissance), Devastation (Apocalypse, Inferno, Genie and Bomb) and Sickness (Addiction and Smoking)