Depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia (CDSS): Genetic vulnerability and sex effects

The present study compares the occurrence of depressive symptoms evaluated by the Calgary Depression Scale for Schizophrenia (CDSS) in patients of Multiplex (MS) and Simplex Schizophrenia families (SS). The Positive and Negative Syndrome Scale (PANSS) was used to evaluate psychopathology. A total of 206 paranoid schizophrenia patients were studied according DSM-IV criteria. The Family Interview for Genetic Studies (FIGS) was used to study the families. A result in the FIGS for a positive family history of schizophrenia was referred as MS (patients); its lack as SS (patients). CDSS scores were compared among MS and SS patients and possible sex differences intra- and inter-groups were explored. In the analysis of our sample (30) 19% of the total persons with schizophrenia group was depressed. The depressive symptoms measured by the CDSS were higher in females and the MS males group. Males from MS group showed more depressive symptoms than males from SS group. No differences with females from both groups were found. Findings in this study underscore the importance of gender and family history in understanding the heterogeneity of schizophrenia. This study suggests proved that sex and familiar history is an important point for studying depressive symptoms.Fil: Martín Reyes, Migdyrai. No especifíca;Fil: Mendoza, Raúl. No especifíca;Fil: Domínguez, Mayelín. No especifíca;Fil: Caballero, Antonio. No especifíca;Fil: Bravo, Tania Marta. No especifíca;Fil: Díaz, Thais. No especifíca;Fil: Gerra, Seidel. No especifíca;Fil: Ibañez, Agustin Mariano. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Diego Portales; ChileFil: Ruiz-Linares, Andres. University College London; Estados Unido

Genetic components of human pain sensitivity: a protocol for a genome-wide association study of experimental pain in healthy volunteers

Introduction Pain constitutes a major component of the global burden of diseases. Recent studies suggest a strong genetic contribution to pain susceptibility and severity. Whereas most of the available evidence relies on candidate gene association or linkage studies, research on the genetic basis of pain sensitivity using genome-wide association studies (GWAS) is still in its infancy. This protocol describes a proposed GWAS on genetic contributions to baseline pain sensitivity and nociceptive sensitisation in a sample of unrelated healthy individuals of mixed Latin American ancestry. Methods and analysis A GWAS on genetic contributions to pain sensitivity in the naïve state and following nociceptive sensitisation will be conducted in unrelated healthy individuals of mixed ancestry. Mechanical and thermal pain sensitivity will be evaluated with a battery of quantitative sensory tests evaluating pain thresholds. In addition, variation in mechanical and thermal sensitisation following topical application of mustard oil to the skin will be evaluated. Ethics and dissemination This study received ethical approval from the University College London research ethics committee (3352/001) and from the bioethics committee of the Odontology Faculty at the University of Antioquia (CONCEPTO 01–2013). Findings will be disseminated to commissioners, clinicians and service users via papers and presentations at international conferences

Automatic landmarking identifies new loci associated with face morphology and implicates Neanderthal introgression in human nasal shape

We report a genome-wide association study of facial features in >6000 Latin Americans based on automatic landmarking of 2D portraits and testing for association with inter-landmark distances. We detected significant associations (P-value <5 × 10−8) at 42 genome regions, nine of which have been previously reported. In follow-up analyses, 26 of the 33 novel regions replicate in East Asians, Europeans, or Africans, and one mouse homologous region influences craniofacial morphology in mice. The novel region in 1q32.3 shows introgression from Neanderthals and we find that the introgressed tract increases nasal height (consistent with the differentiation between Neanderthals and modern humans). Novel regions include candidate genes and genome regulatory elements previously implicated in craniofacial development, and show preferential transcription in cranial neural crest cells. The automated approach used here should simplify the collection of large study samples from across the world, facilitating a cosmopolitan characterization of the genetics of facial features

Recessive distal renal tubular acidosis in Sarawak caused by AE1 mutations

Mutations of the AE1 (SLC4A1, Anion-Exchanger 1) gene that codes for band 3, the renal and red cell anion exchanger, are responsible for many cases of familial distal renal tubular acidosis (dRTA). In Southeast Asia this disease is usually recessive, caused either by homozygosity of a single AE1 mutation or by compound heterozygosity of two different AE1 mutations. We describe two unrelated boys in Sarawak with dRTA associated with compound heterozygosity of AE1 mutations. Both had Southeast Asian ovalocytosis (SAO), a morphological abnormality of red cells caused by a deletion of band 3 residues 400–408. In addition, one boy had a DNA sequence abnormality of band 3 residue (G701D), which has been reported from elsewhere in Southeast Asia. The other boy had the novel sequence abnormality of band 3 (Q759H) and profound hemolytic anemia

Inbreeding, native American ancestry and child mortality:Linking human selection and paediatric medicine

The children of related parents show increased risk of early mortality. The Native American genome typically exhibits long stretches of homozygosity, and Latin Americans are highly heterogeneous regarding the individual burden of homozygosity, the proportion and the type of Native American ancestry. We analysed nationwide mortality and genome-wide genotype data from admixed Chileans to investigate the relationship between common causes of child mortality, homozygosity and Native American ancestry. Results from two-stage linear-Poisson regression revealed a strong association between the sum length of runs of homozygosity (SROH) above 1.5 Megabases (Mb) in each genome and mortality due to intracranial non-traumatic haemorrhage of foetus and newborn (5% increased risk of death per Mb in SROH, P = 1 × 10(−3)) and disorders related to short gestation and low birth weight (P = 3 × 10(−4)). The major indigenous populations in Chile are Aymara–Quechua in the north of the country and the Mapuche–Huilliche in the south. The individual proportion of Aymara–Quechua ancestry was associated with an increased risk of death due to anencephaly and similar malformations (P = 4 × 10(−5)), and the risk of death due to Edwards and Patau trisomy syndromes decreased 4% per 1% Aymara–Quechua ancestry proportion (P = 4 × 10(−4)) and 5% per 1% Mapuche–Huilliche ancestry proportion (P = 2 × 10(−3)). The present results suggest that short gestation, low birth weight and intracranial non-traumatic haemorrhage mediate the negative effect of inbreeding on human selection. Independent validation of the identified associations between common causes of child death, homozygosity and fine-scale ancestry proportions may inform paediatric medicine

Inbreeding, Native American ancestry and child mortality: linking human selection and paediatric medicine

The children of related parents show increased risk of early mortality. The Native American genome typically exhibits long stretches of homozygosity, and Latin Americans are highly heterogeneous regarding the individual burden of homozygosity, the proportion and the type of Native American ancestry. We analysed nationwide mortality and genome-wide genotype data from admixed Chileans to investigate the relationship between common causes of child mortality, homozygosity and Native American ancestry. Results from two-stage linear-Poisson regression revealed a strong association between the sum length of runs of homozygosity (SROH) above 1.5 Megabases (Mb) in each genome and mortality due to intracranial non-traumatic haemorrhage of foetus and newborn (5% increased risk of death per Mb in SROH, P = 1 × 10−3) and disorders related to short gestation and low birth weight (P = 3 × 10−4). The major indigenous populations in Chile are Aymara–Quechua in the north of the country and the Mapuche–Huilliche in the south. The individual proportion of Aymara–Quechua ancestry was associated with an increased risk of death due to anencephaly and similar malformations (P = 4 × 10−5), and the risk of death due to Edwards and Patau trisomy syndromes decreased 4% per 1% Aymara–Quechua ancestry proportion (P = 4 × 10−4) and 5% per 1% Mapuche–Huilliche ancestry proportion (P = 2 × 10−3). The present results suggest that short gestation, low birth weight and intracranial non-traumatic haemorrhage mediate the negative effect of inbreeding on human selection. Independent validation of the identified associations between common causes of child death, homozygosity and fine-scale ancestry proportions may inform paediatric medicine.Fil: Koenigstein, Fabienne. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Boekstegers, Felix. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Wilson, James F.. University of Edinburgh; Reino UnidoFil: Fuentes Guajardo, Macarena. Universidad de Tarapacá; ChileFil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; ArgentinaFil: Bedoya Berrío, Gabriel. Universidad de Antioquia; ColombiaFil: Bortolini, Maria Cátira. Universidade Federal do Rio Grande do Sul; BrasilFil: Acuña Alonzo, Victor. Instituto Nacional de Antropología e Historia. Escuela Nacional de Antropología e Historia; MéxicoFil: Gallo, Carla. Universidad Peruana Cayetano Heredia; PerúFil: Ruiz-Linares, Andres. Fudan University; China. Aix-Marseille Université; Francia. Centre National de la Recherche Scientifique; Francia. University College London; Reino UnidoFil: Rothhammer, Francisco. Universidad de Tarapaca. Instituto de Alta Investigación; ChileFil: Lorenzo Bermejo, Justo. Ruprecht Karls Universitat Heidelberg; Alemani

Reconstructing native American migrations from whole-genome and whole-exome data.

There is great scientific and popular interest in understanding the genetic history of populations in the Americas. We wish to understand when different regions of the continent were inhabited, where settlers came from, and how current inhabitants relate genetically to earlier populations. Recent studies unraveled parts of the genetic history of the continent using genotyping arrays and uniparental markers. The 1000 Genomes Project provides a unique opportunity for improving our understanding of population genetic history by providing over a hundred sequenced low coverage genomes and exomes from Colombian (CLM), Mexican-American (MXL), and Puerto Rican (PUR) populations. Here, we explore the genomic contributions of African, European, and especially Native American ancestry to these populations. Estimated Native American ancestry is 48% in MXL, 25% in CLM, and 13% in PUR. Native American ancestry in PUR is most closely related to populations surrounding the Orinoco River basin, confirming the Southern American ancestry of the Taíno people of the Caribbean. We present new methods to estimate the allele frequencies in the Native American fraction of the populations, and model their distribution using a demographic model for three ancestral Native American populations. These ancestral populations likely split in close succession: the most likely scenario, based on a peopling of the Americas 16 thousand years ago (kya), supports that the MXL Ancestors split 12.2kya, with a subsequent split of the ancestors to CLM and PUR 11.7kya. The model also features effective populations of 62,000 in Mexico, 8,700 in Colombia, and 1,900 in Puerto Rico. Modeling Identity-by-descent (IBD) and ancestry tract length, we show that post-contact populations also differ markedly in their effective sizes and migration patterns, with Puerto Rico showing the smallest effective size and the earlier migration from Europe. Finally, we compare IBD and ancestry assignments to find evidence for relatedness among European founders to the three populations

A geometric morphometric approach to the study of variation of shovel-shaped incisors

Objectives: The scoring and analysis of dental nonmetric traits are predominantly accomplished by using the Arizona State University Dental Anthropology System (ASUDAS), a standard protocol based on strict definitions and three‐dimensional dental plaques. However, visual scoring, even when controlled by strict definitions of features, visual reference, and the experience of the observer, includes an unavoidable part of subjectivity. In this methodological contribution, we propose a new quantitative geometric morphometric approach to quickly and efficiently assess the variation of shoveling in modern human maxillary central incisors (UI1). Materials and methods: We analyzed 87 modern human UI1s by means of virtual imaging and the ASU‐UI1 dental plaque grades using geometric morphometrics by placing semilandmarks on the labial crown aspect. The modern human sample was composed of individuals from Europe, Africa, and Asia and included representatives of all seven grades defined by the ASUDAS method. Results: Our results highlighted some limitations in the use of the current UI1 ASUDAS plaque, indicating that it did not necessarily represent an objective gradient of expression of a nonmetric tooth feature. Rating of shoveling tended to be more prone to intra‐ and interobserver bias for the highest grades. In addition, our analyses suggest that the observers were strongly influenced by the depth of the lingual crown aspect when assessing the shoveling. Discussion: In this context, our results provide a reliable and reproducible framework reinforced by statistical results supporting the fact that open scale numerical measurements can complement the ASUDAS method

Dental size variation in admixed Latin Americans: effects of age, sex and genomic ancestry

Dental size variation in modern humans has been assessed from regional to worldwide scales, especially under microevolutionary and forensic contexts. Despite this, populations of mixed continental ancestry such as contemporary Latin Americans remain unexplored. In the present study we investigated a large Latin American sample from Colombia (N = 804) and obtained buccolingual and mesiodistal diameters and three indices for maxillary and mandibular teeth (except third molars). We evaluated the correlation between 28 dental measurements (and three indices) with age, sex and genomic ancestry (estimated using genome-wide SNP data). In addition, we explored correlation patterns between dental measurements and the biological affinities, based on these measurements, between two Latin American samples (Colombians and Mexicans) and three putative parental populations: Central and South Native Americans, western Europeans and western Africans through PCA and DFA. Our results indicate that Latin Americans have high dental size diversity, overlapping the variation exhibited by the parental populations. Several dental dimensions and indices have significant correlations with sex and age. Western Europeans presented closer biological affinities with Colombians, and the European genomic ancestry exhibited the highest correlations with tooth size. Correlations between tooth measurements reveal distinct dental modules, as well as a higher integration of postcanine dentition. The effects on dental size of age, sex and genomic ancestry is of relevance for forensic, biohistorical and microevolutionary studies in Latin Americans

Contribution of common and rare variants to bipolar disorder susceptibility in extended pedigrees from population isolates.

Current evidence from case/control studies indicates that genetic risk for psychiatric disorders derives primarily from numerous common variants, each with a small phenotypic impact. The literature describing apparent segregation of bipolar disorder (BP) in numerous multigenerational pedigrees suggests that, in such families, large-effect inherited variants might play a greater role. To identify roles of rare and common variants on BP, we conducted genetic analyses in 26 Colombia and Costa Rica pedigrees ascertained for bipolar disorder 1 (BP1), the most severe and heritable form of BP. In these pedigrees, we performed microarray SNP genotyping of 838 individuals and high-coverage whole-genome sequencing of 449 individuals. We compared polygenic risk scores (PRS), estimated using the latest BP1 genome-wide association study (GWAS) summary statistics, between BP1 individuals and related controls. We also evaluated whether BP1 individuals had a higher burden of rare deleterious single-nucleotide variants (SNVs) and rare copy number variants (CNVs) in a set of genes related to BP1. We found that compared with unaffected relatives, BP1 individuals had higher PRS estimated from BP1 GWAS statistics (P = 0.001 ~ 0.007) and displayed modest increase in burdens of rare deleterious SNVs (P = 0.047) and rare CNVs (P = 0.002 ~ 0.033) in genes related to BP1. We did not observe rare variants segregating in the pedigrees. These results suggest that small-to-moderate effect rare and common variants are more likely to contribute to BP1 risk in these extended pedigrees than a few large-effect rare variants