Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits

Faith in history: Armenians rebuilding community in Cyprus and London.

This thesis explores the rebuilding of Armenian community in Cyprus following dispersion from their homelands in the early twentieth century. It continues with later disruptions, decreasing population, and again rebuilding both in Cyprus and in London, England where many Armenian Cypriots resettled in the 1960s. The focus is on the process of culture, the passing of values and ideas over several generations in diaspora. Armenians in these communities place a formal emphasis on their church, language, and history as the cornerstones of their culture. Changing views of these aspects are examined in the context of family and community interactions and relationships. Fieldwork was carried out in Nicosia, Larnaca, and Limassol, Cyprus and in London, England, over five years (including a total of eight months in Cyprus). Life histories form the base for the early, ethnohistorical chapters. Observation and participation in community events, informal conversations, visits to churches, schools, clubs, and homes were essential. Written sources were also used (e.g. letters, church documents), most notably, a set of memoirs compiled especially for this project. Common themes emerged which provide a "prior text" for the two communities, most prominently, insecurity, sacrifice, and survival. Survival includes a stress on a 2,500 year Armenian history which itself becomes a social charter, providing an anchor in the face of insecurity and the necessary flexibility of diaspora life. The continued longevity of the Armenian people and the "correct" interpretation of history in the face of perceived injustices provides a moral cause, a call for sacrifice. The thesis concludes with an examination of the overlap between nationalism and religion, of the interplay of cultural change and religious belief, the dual roles, spiritual and functional, of the national church and the nature of faith in both.Ph.D.AnthropologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/105424/1/9023615.pdfDescription of 9023615.pdf : Restricted to UM users only

Genome-wide studies of verbal declarative memory in nondemented older people: the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium

Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting.; We conducted genome-wide association studies for paragraph or word list delayed recall in 19 cohorts from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium, comprising 29,076 dementia- and stroke-free individuals of European descent, aged ≥45 years. Replication of suggestive associations (p < 5 × 10(-6)) was sought in 10,617 participants of European descent, 3811 African-Americans, and 1561 young adults.; rs4420638, near APOE, was associated with poorer delayed recall performance in discovery (p = 5.57 × 10(-10)) and replication cohorts (p = 5.65 × 10(-8)). This association was stronger for paragraph than word list delayed recall and in the oldest persons. Two associations with specific tests, in subsets of the total sample, reached genome-wide significance in combined analyses of discovery and replication (rs11074779 [HS3ST4], p = 3.11 × 10(-8), and rs6813517 [SPOCK3], p = 2.58 × 10(-8)) near genes involved in immune response. A genetic score combining 58 independent suggestive memory risk variants was associated with increasing Alzheimer disease pathology in 725 autopsy samples. Association of memory risk loci with gene expression in 138 human hippocampus samples showed cis-associations with WDR48 and CLDN5, both related to ubiquitin metabolism.; This largest study to date exploring the genetics of memory function in ~40,000 older individuals revealed genome-wide associations and suggested an involvement of immune and ubiquitin pathways

Genome-wide studies of verbal declarative memory in nondemented older people: The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium

BACKGROUND: Memory performance in older persons can reflect genetic influences on cognitive function and dementing processes. We aimed to identify genetic contributions to verbal declarative memory in a community setting. ME

Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Background: Recently, common genetic risk factors for intracranial aneurysm (IA) and aneurysmal subarachnoid hemorrhage (ASAH) were found to explain a large amount of disease heritability and therefore have potential to be used for genetic risk prediction. We constructed a genetic risk score to (1) predict ASAH incidence and IA presence (combined set of unruptured IA and ASAH) and (2) assess its association with patient characteristics. Methods: A genetic risk score incorporating genetic association data for IA and 17 traits related to IA (so-called metaGRS) was created using 1161 IA cases and 407 392 controls from the UK Biobank population study. The metaGRS was validated in combination with risk factors blood pressure, sex, and smoking in 828 IA cases and 68 568 controls from the Nordic HUNT population study. Furthermore, we assessed association between the metaGRS and patient characteristics in a cohort of 5560 IA patients. Results: Per SD increase of metaGRS, the hazard ratio for ASAH incidence was 1.34 (95% CI, 1.20-1.51) and the odds ratio for IA presence 1.09 (95% CI, 1.01-1.18). Upon including the metaGRS on top of clinical risk factors, the concordance index to predict ASAH hazard increased from 0.63 (95% CI, 0.59-0.67) to 0.65 (95% CI, 0.62-0.69), while prediction of IA presence did not improve. The metaGRS was statistically significantly associated with age at ASAH (β=-4.82×10-3per year [95% CI, -6.49×10-3to -3.14×10-3]; P=1.82×10-8), and location of IA at the internal carotid artery (odds ratio=0.92 [95% CI, 0.86-0.98]; P=0.0041). Conclusions: The metaGRS was predictive of ASAH incidence, although with limited added value over clinical risk factors. The metaGRS was not predictive of IA presence. Therefore, we do not recommend using this metaGRS in daily clinical care. Genetic risk does partly explain the clinical heterogeneity of IA warranting prioritization of clinical heterogeneity in future genetic prediction studies of IA and ASAH