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14 results on '"Gallo, Carla"'

1. The Simons Genome Diversity Project: 300 genomes from 142 diverse populations

Author

Mallick, Swapan, Li, Heng, Lipson, Mark, Mathieson, Iain, Gymrek, Melissa, Racimo, Fernando, Zhao, Mengyao, Chennagiri, Niru, Nordenfelt, Susanne, Tandon, Arti, Skoglund, Pontus, Lazaridis, Iosif, Sankararaman, Sriram, Fu, Qiaomei, Rohland, Nadin, Renaud, Gabriel, Erlich, Yaniv, Willems, Thomas, Gallo, Carla, Spence, Jeffrey P, Song, Yun S, Poletti, Giovanni, Balloux, Francois, van Driem, George, de Knijff, Peter, Romero, Irene Gallego, Jha, Aashish R, Behar, Doron M, Bravi, Claudio M, Capelli, Cristian, Hervig, Tor, Moreno-Estrada, Andres, Posukh, Olga L, Balanovska, Elena, Balanovsky, Oleg, Karachanak-Yankova, Sena, Sahakyan, Hovhannes, Toncheva, Draga, Yepiskoposyan, Levon, Tyler-Smith, Chris, Xue, Yali, Abdullah, M Syafiq, Ruiz-Linares, Andres, Beall, Cynthia M, Di Rienzo, Anna, Jeong, Choongwon, Starikovskaya, Elena B, Metspalu, Ene, Parik, Jüri, Villems, Richard, Henn, Brenna M, Hodoglugil, Ugur, Mahley, Robert, Sajantila, Antti, Stamatoyannopoulos, George, Wee, Joseph TS, Khusainova, Rita, Khusnutdinova, Elza, Litvinov, Sergey, Ayodo, George, Comas, David, Hammer, Michael F, Kivisild, Toomas, Klitz, William, Winkler, Cheryl A, Labuda, Damian, Bamshad, Michael, Jorde, Lynn B, Tishkoff, Sarah A, Watkins, W Scott, Metspalu, Mait, Dryomov, Stanislav, Sukernik, Rem, Singh, Lalji, Thangaraj, Kumarasamy, Pääbo, Svante, Kelso, Janet, Patterson, Nick, and Reich, David

Subjects
Human Genome, Genetics, Animals, Australia, Black People, Datasets as Topic, Genetic Variation, Genetics, Population, Genome, Human, Genomics, History, Ancient, Human Migration, Humans, Mutation Rate, Native Hawaiian or Other Pacific Islander, Neanderthals, New Guinea, Phylogeny, Racial Groups, Sequence Analysis, DNA, Species Specificity, Time Factors, General Science & Technology
Abstract

Here we report the Simons Genome Diversity Project data set: high quality genomes from 300 individuals from 142 diverse populations. These genomes include at least 5.8 million base pairs that are not present in the human reference genome. Our analysis reveals key features of the landscape of human genome variation, including that the rate of accumulation of mutations has accelerated by about 5% in non-Africans compared to Africans since divergence. We show that the ancestors of some pairs of present-day human populations were substantially separated by 100,000 years ago, well before the archaeologically attested onset of behavioural modernity. We also demonstrate that indigenous Australians, New Guineans and Andamanese do not derive substantial ancestry from an early dispersal of modern humans; instead, their modern human ancestry is consistent with coming from the same source as that of other non-Africans.

Published
2016

2. Reconstructing Native American population history

Author

Reich, David, Patterson, Nick, Campbell, Desmond, Tandon, Arti, Mazieres, Stéphane, Ray, Nicolas, Parra, Maria V, Rojas, Winston, Duque, Constanza, Mesa, Natalia, García, Luis F, Triana, Omar, Blair, Silvia, Maestre, Amanda, Dib, Juan C, Bravi, Claudio M, Bailliet, Graciela, Corach, Daniel, Hünemeier, Tábita, Bortolini, Maria Cátira, Salzano, Francisco M, Petzl-Erler, María Luiza, Acuña-Alonzo, Victor, Aguilar-Salinas, Carlos, Canizales-Quinteros, Samuel, Tusié-Luna, Teresa, Riba, Laura, Rodríguez-Cruz, Maricela, Lopez-Alarcón, Mardia, Coral-Vazquez, Ramón, Canto-Cetina, Thelma, Silva-Zolezzi, Irma, Fernandez-Lopez, Juan Carlos, Contreras, Alejandra V, Jimenez-Sanchez, Gerardo, Gómez-Vázquez, Maria José, Molina, Julio, Carracedo, Ángel, Salas, Antonio, Gallo, Carla, Poletti, Giovanni, Witonsky, David B, Alkorta-Aranburu, Gorka, Sukernik, Rem I, Osipova, Ludmila, Fedorova, Sardana A, Vasquez, René, Villena, Mercedes, Moreau, Claudia, Barrantes, Ramiro, Pauls, David, Excoffier, Laurent, Bedoya, Gabriel, Rothhammer, Francisco, Dugoujon, Jean-Michel, Larrouy, Georges, Klitz, William, Labuda, Damian, Kidd, Judith, Kidd, Kenneth, Di Rienzo, Anna, Freimer, Nelson B, Price, Alkes L, and Ruiz-Linares, Andrés

Subjects
Biological Sciences, Genetics, History, Heritage and Archaeology, Human Society, Historical Studies, Anthropology, American Indian or Alaska Native, Americas, Asia, Cluster Analysis, Emigration and Immigration, Gene Flow, Genetics, Population, History, Ancient, Humans, Indians, North American, Models, Genetic, Phylogeny, Polymorphism, Single Nucleotide, Siberia, General Science & Technology
Abstract

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved. One contentious issue is whether the settlement occurred by means of a single migration or multiple streams of migration from Siberia. The pattern of dispersals within the Americas is also poorly understood. To address these questions at a higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. Here we show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call 'First American'. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan speakers on both sides of the Panama isthmus, who have ancestry from both North and South America.

Published
2012

3. Geographic patterns of genome admixture in Latin American Mestizos.

Author

Wang, Sijia, Ray, Nicolas, Rojas, Winston, Parra, Maria V, Bedoya, Gabriel, Gallo, Carla, Poletti, Giovanni, Mazzotti, Guido, Hill, Kim, Hurtado, Ana M, Camrena, Beatriz, Nicolini, Humberto, Klitz, William, Barrantes, Ramiro, Molina, Julio A, Freimer, Nelson B, Bortolini, Maria Cátira, Salzano, Francisco M, Petzl-Erler, Maria L, Tsuneto, Luiza T, Dipierri, José E, Alfaro, Emma L, Bailliet, Graciela, Bianchi, Nestor O, Llop, Elena, Rothhammer, Francisco, Excoffier, Laurent, and Ruiz-Linares, Andrés

Subjects
Chromosomes, Human, X, Humans, Genetics, Population, Microsatellite Repeats, Heterozygote, Genome, Human, African Continental Ancestry Group, American Native Continental Ancestry Group, European Continental Ancestry Group, Latin America, Female, Male, Genetic Variation, Chromosomes, Human, X, Genetics, Population, Genome, Developmental Biology
Abstract

The large and diverse population of Latin America is potentially a powerful resource for elucidating the genetic basis of complex traits through admixture mapping. However, no genome-wide characterization of admixture across Latin America has yet been attempted. Here, we report an analysis of admixture in thirteen Mestizo populations (i.e. in regions of mainly European and Native settlement) from seven countries in Latin America based on data for 678 autosomal and 29 X-chromosome microsatellites. We found extensive variation in Native American and European ancestry (and generally low levels of African ancestry) among populations and individuals, and evidence that admixture across Latin America has often involved predominantly European men and both Native and African women. An admixture analysis allowing for Native American population subdivision revealed a differentiation of the Native American ancestry amongst Mestizos. This observation is consistent with the genetic structure of pre-Columbian populations and with admixture having involved Natives from the area where the Mestizo examined are located. Our findings agree with available information on the demographic history of Latin America and have a number of implications for the design of association studies in population from the region.

Published
2008

4. Expression of stromal elements of prostatic adenocarcinoma in different gleason scores 1

Author

Osorio, Clarice Fraga Esteves Maciel, Costa, Waldemar Silva, Gallo, Carla Braga Mano, and Sampaio, Francisco José Barcellos

Subjects
Aged, 80 and over, Male, Histology, Prostatic Neoplasms, Muscle, Smooth, Adenocarcinoma, Middle Aged, Elastic Tissue, Reference Values, Tissue Array Analysis, Blood Vessels, Humans, Original Article, Clinical Investigation, Collagen, Neoplasm Grading, Stromal Cells, Aged, Retrospective Studies
Abstract

Purpose: To quantify and compare the expression of stromal elements in prostate adenocarcinoma of different Gleason scores with non-tumor area (control). Methods: We obtained 132 specimens from samples of prostate peripheral and transition zone. We analyzed the following elements of the extracellular matrix: collagen fibers, elastic system, smooth muscle fibers and blood vessels. The tumor area and non-tumor area (control) of the TMA (tissue microarray) were photographed and analyzed using the ImageJ software. Results: The comparison between the tumor area and the non-tumor area showed significant differences between stromal prostate elements. There was an increase of collagen fibers in the tumor area, mainly in Gleason 7. Elastic system fibers showed similar result, also from the Gleason 7. Blood vessels showed a significant increase occurred in all analyzed groups. The muscle fibers exhibited a different behavior, with a decrease in relation to the tumor area. Conclusions: There is a significant difference between the extracellular matrix in prostate cancer compared to the non-tumor area (control) especially in Gleason 7. Important modifications of the prostatic stromal elements strongly correlate with different Gleason scores and can contribute to predict the pathological staging of prostate cancer.

Published
2019

5. A GWAS in Latin Americans highlights the convergent evolution of lighter skin pigmentation in Eurasia

Author

Adhikari, Kaustubh, Mendoza-Revilla, Javier, Sohail, Anood, Fuentes-Guajardo, Macarena, Lampert, Jodie, Chacón-Duque, Juan Camilo, Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Everardo, Paola, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Silva de Cerqueira, Caio C., Hunemeier, Tábita, Ramallo, Virginia, Schuler-Faccini, Lavinia, Salzano, Francisco M., Gonzalez-José, Rolando, Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Rothhammer, Francisco, Tobin, Desmond J., Fumagalli, Matteo, Balding, David, Ruiz-Linares, Andrés, Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), Dept of Genetics, Evolution and Environment [London] (UCL-GEE), University College of London [London] (UCL), Molecular Genetics Laboratory, Escuela Nacional de Antropologia y Historia, Departamento de Genética, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS)-Instituto de Biociencias, Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Laboratorio de Genética Molecular, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Facultad de Medicina & Instituto de Alta Investigacion, Universidad de Tarapaca-Universidade de Chile, Center for Skin Sciences, and University of Bradford

Subjects
epistasis, Male, POSITIVE SELECTION, genetic association, EUROPEANS, [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, LOCI, purl.org/pe-repo/ocde/ford#1.03.00 [https], Skin Pigmentation, chromosome 1q, human experiment, quantitative trait locus, Ethnicity, skin color, GWAS, Guanine Nucleotide Exchange Factors, genetics, lcsh:Science, ADAPTATION, POPULATION, ComputingMilieux_MISCELLANEOUS, transcription factor YY1, HERC2 protein, human, allele, Biological Evolution, chromosome 20q, Science & Technology - Other Topics, phenotype, Science, solar radiation, European Continental Ancestry Group, Quantitative Trait Loci, metabotropic receptor 5, White People, Article, medical photography, Ciencias Biológicas, Asian People, human genome, Humans, COLOR, human, normal human, GENOME-WIDE ASSOCIATION, convergent evolution, POLYMORPHISMS, Alleles, Science & Technology, binding site, human cell, Membrane Transport Proteins, Epistasis, Genetic, gene linkage disequilibrium, carrier protein, Genetics, Population, Latin America, hair root, lcsh:Q, GRM5 protein, human, melanocyte, [SDV]Life Sciences [q-bio], Gene Expression, purl.org/becyt/ford/1 [https], ethnic group, Genética y Herencia, Gene Frequency, single nucleotide polymorphism, guanine nucleotide exchange factor, membrane protein, exon, transcription factor EMX2, Eye Color, MFSD12 protein, human, OCA2 protein, human, phenotypic variation, melanin, ADMIXTURE, Multidisciplinary Sciences, female, immunohistochemistry, Female, CIENCIAS NATURALES Y EXACTAS, amino acid substitution, Asian Continental Ancestry Group, gene locus, intron, Ubiquitin-Protein Ligases, purl.org/pe-repo/ocde/ford#1.06.03 [https], Receptor, Metabotropic Glutamate 5, Ethnic Groups, ANCESTRY, Caucasian, Polymorphism, Single Nucleotide, South and Central America, MD Multidisciplinary, evolution, controlled study, purl.org/becyt/ford/1.6 [https], genome-wide association study, Genome, Human, population genetics, Membrane Proteins, human tissue, LATIN AMERICANS, chromosome 22q, Latin American medicine, purl.org/pe-repo/ocde/ford#1.04.00 [https], sense organs, MERCAPTOPYRUVATE SULFURTRANSFERASE, Genome-Wide Association Study
Abstract

We report a genome-wide association scan in >6,000 Latin Americans for pigmentation of skin and eyes. We found eighteen signals of association at twelve genomic regions. These include one novel locus for skin pigmentation (in 10q26) and three novel loci for eye pigmentation (in 1q32, 20q13 and 22q12). We demonstrate the presence of multiple independent signals of association in the 11q14 and 15q13 regions (comprising the GRM5/TYR and HERC2/OCA2 genes, respectively) and several epistatic interactions among independently associated alleles. Strongest association with skin pigmentation at 19p13 was observed for an Y182H missense variant (common only in East Asians and Native Americans) in MFSD12, a gene recently associated with skin pigmentation in Africans. We show that the frequency of the derived allele at Y182H is significantly correlated with lower solar radiation intensity in East Asia and infer that MFSD12 was under selection in East Asians, probably after their split from Europeans., Pigmentation variation in humans is influenced by complex genetic architecture in different populations. Here, the authors perform a genome-wide association analysis involving > 6,000 Latin Americans for pigmentation of skin and eyes, and identify known and novel genetic associations.

Published
2019
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6. Obesity, genomic ancestry, and socioeconomic variables in Latin American mestizos

Author

Ruderman, Anahí, Pérez, Luis, Adhikari, Kaustubh, Navarro, Pablo, Ramallo, Virginia, Gallo, Carla, Poletti, Giovanni, Bedoya, Gabriel, Bortolini, Maria, Acuña-Alonzo, Victor, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Ruiz-Linares, Andrés, González-José, Rolando, Acuña‐Alonzo, Victor, Canizales‐Quinteros, Samuel, Ruiz‐Linares, Andres, González‐José, Rolando, Dept of Genetics, Evolution and Environment [London] (UCL-GEE), University College of London [London] (UCL), Anthropologie bio-culturelle, Droit, Ethique et Santé (ADES), Aix Marseille Université (AMU)-EFS ALPES MEDITERRANEE-Centre National de la Recherche Scientifique (CNRS), State Key Laboratory of Genetics Engineering & MOE Key Laboratory of Contemporary Anthropology, Fudan University [Shanghai]-School of Life Sciences, Laboratorio de Genética Molecular, Universidad de Antioquia = University of Antioquia [Medellín, Colombia], Departamento de Genética, Universidade Federal do Rio Grande do Sul [Porto Alegre] (UFRGS)-Instituto de Biociencias, Molecular Genetics Laboratory, Escuela Nacional de Antropologia y Historia, Unit of Molecular Biology and Genomic Medicine, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Facultad de Medicina & Instituto de Alta Investigacion, Universidad de Tarapaca-Universidade de Chile, and Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET)

Subjects
Male, [SDV]Life Sciences [q-bio], [SHS.ANTHRO-BIO]Humanities and Social Sciences/Biological anthropology, Overweight, purl.org/becyt/ford/1 [https], 0302 clinical medicine, Waist–hip ratio, hemic and lymphatic diseases, Peru, Prevalence, 0601 history and archaeology, Chile, ComputingMilieux_MISCELLANEOUS, 2. Zero hunger, Waist-to-height ratio, education.field_of_study, 1. No poverty, Genomic ancestry, 06 humanities and the arts, Admixed populations, Middle Aged, population characteristics, Female, Anatomy, medicine.symptom, CIENCIAS NATURALES Y EXACTAS, Brazil, Adult, Waist, Otras Ciencias Biológicas, Population, education, 030209 endocrinology & metabolism, Colombia, Ciencias Biológicas, 03 medical and health sciences, Young Adult, Genetics, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Obesity, purl.org/becyt/ford/1.6 [https], neoplasms, Mexico, Ecology, Evolution, Behavior and Systematics, 060101 anthropology, business.industry, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Anthropometry, medicine.disease, eye diseases, Latin America, Social Class, Socioeconomic Factors, Anthropology, business, Body mass index, Demography
Abstract

Objectives: This article aims to assess the contribution of genomic ancestry and socioeconomic status to obesity in a sample of admixed Latin Americans. Methods: The study comprised 6776 adult volunteers from Brazil, Chile, Colombia, Mexico, and Peru. Each volunteer completed a questionnaire about socioeconomic variables. Anthropometric variables such as weight, height, waist, and hip circumference were measured to calculate body indices: body mass index, waist-to-hip ratio and waist-to-height ratio (WHtR). Genetic data were extracted from blood samples, and ancestry was estimated using chip genotypes. Multiple linear regression was used to evaluate the relationship between the indices and ancestry, educational level, and economic well-being. The body indices were dichotomized to obesity indices by using appropriate thresholds. Odds ratios were calculated for each obesity index. Results: The sample showed high percentages of obesity by all measurements. However, indices did not overlap consistently when classifying obesity. WHtR resulted in the highest prevalence of obesity. Overall, women with low education level and men with high economic wellness were more likely to be obese. American ancestry was statistically associated with obesity indices, although to a lesser extent than socioeconomic variables. Conclusions: The proportion of obesity was heavily dependent on the index and the population. Genomic ancestry has a significant influence on the anthropometric measurements, especially on central adiposity. As a whole, we detected a large interpopulation variation that suggests that better approaches to overweight and obesity phenotypes are needed in order to obtain more precise reference values. Fil: Ruderman, Anahí. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Perez, Luis Orlando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Adhikari, Kaustubh. Colegio Universitario de Londres; Reino Unido. Open University; Reino Unido Fil: Navarro, Pablo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Ramallo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú Fil: Bedoya Berrío, Gabriel. Universidad de Antioquia; Colombia Fil: Bortolini, María Cátira. Universidade Federal do Rio Grande do Sul; Brasil Fil: Acuña Alonzo, Victor. Instituto Nacional de Antropología E Historia; México Fil: Canizales Quinteros, Samuel. Instituto Nacional de Medicina Genómica; México Fil: Rothhammer, Francisco. Universidad de Chile; Chile Fil: Ruiz-Linares, Andres. Colegio Universitario de Londres; Reino Unido. Fudan University; China Fil: González José, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentina

Published
2018
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7. Subtypes of Native American ancestry and leading causes of death: Mapuche ancestry-specific associations with gallbladder cancer risk in Chile

Author

Bermejo, Justo Lorenzo, Boekstegers, Felix, González Silos, Rosa, Marcelain, Katherine, Baez Benavides, Pablo, Barahona Ponce, Carol, Müller, Bettina, Ferreccio, Catterina, Koshiol, Jill, Fischer, Christine, Peil, Barbara, Sinsheimer, Janet, Fuentes Guajardo, Macarena, Barajas, Olga, González José, Rolando, Bedoya Berrío, Gabriel de Jesús, Bortolini, Maria Cátira, Canizales Quinteros, Samuel, Gallo, Carla, Ruíz Linares, Andres, and Rothhammer, Francisco

Subjects
Male, Skin Neoplasms, Ciencias de la Salud, Social Sciences, Geographical locations, Sociology, CHILE, Risk Factors, Native Americans, Neoplasms, Medicine and Health Sciences, Ethnicities, Chile, Latin America/epidemiology, Population groupings, Oncology, purl.org/becyt/ford/3 [https], ANCESTRIA, Female, Gallbladder Neoplasms, Research Article, Adult, CIENCIAS MÉDICAS Y DE LA SALUD, lcsh:QH426-470, Adolescent, Genotype, Death Rates, purl.org/pe-repo/ocde/ford#1.06.03 [https], Malignant Skin Neoplasms, Dermatology, Gallbladder Neoplasms/genetics/mortality, Education, purl.org/becyt/ford/3.3 [https], Gastrointestinal Tumors, Genetics, Humans, Genética de Población, Educational Attainment, Demography, Chile (Country), Salud Ocupacional, Genome, Human, Cancers and Neoplasms, Gallbladder Cancer, Biology and Life Sciences, GENOMICA, South America, Mapuche Indians, lcsh:Genetics, Genetics, Population, Latin America, Mapuches, Indians, North American/genetics, Genetics of Disease, Indians, North American, CANCER DE VESICULA, People and places, Neoplasias de la Vesícula Biliar, purl.org/pe-repo/ocde/ford#1.06.07 [https], Genome-Wide Association Study
Abstract

Latin Americans are highly heterogeneous regarding the type of Native American ancestry. Consideration of specific associations with common diseases may lead to substantial advances in unraveling of disease etiology and disease prevention. Here we investigate possible associations between the type of Native American ancestry and leading causes of death. After an aggregate-data study based on genome-wide genotype data from 1805 admixed Chileans and 639,789 deaths, we validate an identified association with gallbladder cancer relying on individual data from 64 gallbladder cancer patients, with and without a family history, and 170 healthy controls. Native American proportions were markedly underestimated when the two main types of Native American ancestry in Chile, originated from the Mapuche and Aymara indigenous peoples, were combined together. Consideration of the type of Native American ancestry was crucial to identify disease associations. Native American ancestry showed no association with gallbladder cancer mortality (P = 0.26). By contrast, each 1% increase in the Mapuche proportion represented a 3.7% increased mortality risk by gallbladder cancer (95%CI 3.1–4.3%, P = 6×10−27). Individual-data results and extensive sensitivity analyses confirmed the association between Mapuche ancestry and gallbladder cancer. Increasing Mapuche proportions were also associated with an increased mortality due to asthma and, interestingly, with a decreased mortality by diabetes. The mortality due to skin, bladder, larynx, bronchus and lung cancers increased with increasing Aymara proportions. Described methods should be considered in future studies on human population genetics and human health. Complementary individual-based studies are needed to apportion the genetic and non-genetic components of associations identified relying on aggregate-data., Author summary A lot of attention has been paid to Latino heterogeneity related to individual proportions of Native American, European and African ancestry. The importance of the type of Native American ancestry for health, however, has hardly been studied. Here we examined genetic data from 2,039 admixed Chileans to investigate possible associations between top causes of death and the two major types of Native American ancestry in Chile. Our findings demonstrate the necessity of suitable surrogates for ancestry estimation which mirror the actual composition of the study population, and the advantage of considering fine-scale Latino heterogeneity for unraveling of disease etiology and personalized healthcare.

Published
2016

8. A genome-wide association scan implicates DCHS2, RUNX2, GLI3, PAX1 and EDAR in human facial variation

Author

Adhikari, Kaustubh, Fuentes-Guajardo, Macarena, Quinto-Sánchez, Mirsha, Mendoza-Revilla, Javier, Camilo Chacón-Duque, Juan, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Lozano, Rodrigo Barquera, Pérez, Gastón Macín, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Cheeseman, Michael, Rosique, Javier, Bedoya, Gabriel, Rothhammer, Francisco, Headon, Denis, González-José, Rolando, Balding, David, and Ruiz-Linares, Andrés

Subjects
Adult, Population genetics, Science, purl.org/pe-repo/ocde/ford#1.06.03 [https], Otras Ciencias Biológicas, purl.org/pe-repo/ocde/ford#1.03.00 [https], Cadherin Related Proteins, morphogenesis, Core Binding Factor Alpha 1 Subunit, Nerve Tissue Proteins, Paired Box Transcription Factors/genetics, Polymorphism, Single Nucleotide, Article, purl.org/becyt/ford/1 [https], Core Binding Factor Alpha 1 Subunit/genetics, Ciencias Biológicas, Mice, Young Adult, Zinc Finger Protein Gli3, Paired Box Transcription Factors, Animals, Humans, Nerve Tissue Proteins/genetics, purl.org/becyt/ford/1.6 [https], Maxillofacial Development, Edar Receptor, Maxillofacial Development/genetics, Anatomic Variation, Zinc Finger Protein Gli3/genetics, Edar Receptor/genetics, stomatognathic diseases, Latin America, Cadherin Related Proteins/genetics, Face, genome-wide association studies, purl.org/pe-repo/ocde/ford#1.04.00 [https], Face/anatomy & histology, CIENCIAS NATURALES Y EXACTAS, Genome-Wide Association Study
Abstract

We report a genome-wide association scan for facial features in ∼6,000 Latin Americans. We evaluated 14 traits on an ordinal scale and found significant association (P values, Humans show great diversity in facial appearance and this variation is highly heritable. Here, Andres Ruiz-Linares and colleagues examined facial features in admixed Latin Americans and identify genome-wide associations for 14 facial traits, including four gene loci (RUNX2, GLI3, DCHS2 and PAX1) influencing nose morphology.

Published
2016
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9. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features

Author

Adhikari, Kaustubh, Fontanil, Tania, Cal, Santiago, Mendoza-Revilla, Javier, Fuentes-Guajardo, Macarena, Chacón-Duque, Juan-Camilo, Al-Saadi, Farah, Johansson, Jeanette A., Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Gonzalez-José, Rolando, Headon, Denis, López-Otín, Carlos, Tobin, Desmond J., Balding, David, and Ruiz-Linares, Andrés

Subjects
Male, Science, Otras Ciencias Biológicas, purl.org/pe-repo/ocde/ford#1.06.03 [https], purl.org/pe-repo/ocde/ford#1.03.00 [https], Article, purl.org/becyt/ford/1 [https], Ciencias Biológicas, Scalp/physiology, Humans, purl.org/becyt/ford/1.6 [https], Scalp, integumentary system, Continental Population Groups, Gene Expression Regulation/physiology, Racial Groups, population genetics, Genetic Variation, Face/physiology, Gene Expression Regulation, Face, genome-wide association studies, purl.org/pe-repo/ocde/ford#1.04.00 [https], Female, sense organs, CIENCIAS NATURALES Y EXACTAS, Hair, Genome-Wide Association Study, Hair/growth & development
Abstract

We report a genome-wide association scan in over 6,000 Latin Americans for features of scalp hair (shape, colour, greying, balding) and facial hair (beard thickness, monobrow, eyebrow thickness). We found 18 signals of association reaching genome-wide significance (P values 5 × 10−8 to 3 × 10−119), including 10 novel associations. These include novel loci for scalp hair shape and balding, and the first reported loci for hair greying, monobrow, eyebrow and beard thickness. A newly identified locus influencing hair shape includes a Q30R substitution in the Protease Serine S1 family member 53 (PRSS53). We demonstrate that this enzyme is highly expressed in the hair follicle, especially the inner root sheath, and that the Q30R substitution affects enzyme processing and secretion. The genome regions associated with hair features are enriched for signals of selection, consistent with proposals regarding the evolution of human hair., By examining Latin American individuals of mixed European, Native American and African ancestry, Adhikari et al. identify novel loci influencing various features of facial and scalp hair. The study also provides experimental evidence that one of the implicated genes (PRSS53) is expressed in the hair follicle and that the top associated variant alters processing of this enzyme.

Published
2016
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10. A genome-wide association study identifies multiple loci for variation in human ear morphology

Author

Adhikari, Kaustubh, Reales, Guillermo, Smith, Andrew J. P., Konka, Esra, Palmen, Jutta, Quinto-Sanchez, Mirsha, Acuña-Alonzo, Victor, Jaramillo, Claudia, Arias, William, Fuentes, Macarena, Pizarro, María, Barquera Lozano, Rodrigo, Macín Pérez, Gastón, Gómez-Valdés, Jorge, Villamil-Ramírez, Hugo, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Hurtado, Malena, Villegas, Valeria, Granja, Vanessa, Gallo, Carla, Poletti, Giovanni, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria- Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Calderón, Rosario, Rosique, Javier, Cheeseman, Michael, Bhutta, Mahmood F., Humphries, Steve E., Gonzalez-José, Rolando, Headon, Denis, Balding, David, and Ruiz-Linares, Andrés

Subjects
Adult, Male, Adolescent, Genotype, purl.org/pe-repo/ocde/ford#1.06.03 [https], purl.org/pe-repo/ocde/ford#1.03.00 [https], Polymorphism, Single Nucleotide, Article, White People, Ciencias Biológicas, purl.org/becyt/ford/1 [https], Genética y Herencia, Mice, Young Adult, Cell Line, Tumor, Morphogenesis, Homeodomain Proteins/metabolism, Animals, Humans, European Continental Ancestry Group/genetics, purl.org/becyt/ford/1.6 [https], American Indian or Alaska Native, T-Box Domain Proteins/genetics/metabolism, pinna morphology, Homeodomain Proteins, American Native Continental Ancestry Group/genetics, Edar Receptor, Morphogenesis/genetics, EDAR, Edar Receptor/genetics, Latin America, Phenotype, Ear Auricle/anatomy & histology/embryology, purl.org/pe-repo/ocde/ford#1.04.00 [https], genome-wide association, Female, T-Box Domain Proteins, CIENCIAS NATURALES Y EXACTAS, Ear Auricle, Genome-Wide Association Study
Abstract

Here we report a genome-wide association study for non-pathological pinna morphology in over 5,000 Latin Americans. We find genome-wide significant association at seven genomic regions affecting: lobe size and attachment, folding of antihelix, helix rolling, ear protrusion and antitragus size (linear regression P values 2 × 10−8 to 3 × 10−14). Four traits are associated with a functional variant in the Ectodysplasin A receptor (EDAR) gene, a key regulator of embryonic skin appendage development. We confirm expression of Edar in the developing mouse ear and that Edar-deficient mice have an abnormally shaped pinna. Two traits are associated with SNPs in a region overlapping the T-Box Protein 15 (TBX15) gene, a major determinant of mouse skeletal development. Strongest association in this region is observed for SNP rs17023457 located in an evolutionarily conserved binding site for the transcription factor Cartilage paired-class homeoprotein 1 (CART1), and we confirm that rs17023457 alters in vitro binding of CART1., The shape of the pinna varies widely in the general human population but the genetic basis of this variation is unknown. Here Adhikari et al. conduct a genome-wide association study in Latin Americans and discover seven gene regions influencing pinna morphology, including EDAR and TBX15.

Published
2015
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11. Facial asymmetry and genetic ancestry in Latin American admixed populations

Author

Quinto Sanchez, Mirsha Emmanuel, Adhikari, Kaustubh, Acuña Alonzo, Victor, Cintas, Celia, Silva de Cerqueira, Caio Cesar, Ramallo, Virginia, Castillo, Lucía Daniela, Farrera, Arodi, Jaramillo, Claudia, Williams Arias, Fuentes, Macarena, Everardo, Paola, de Avila, Francisco, Gomez Valdés, Jorge, Hünemeier, Tábita, Gibbon, Shara, Gallo, Carla, Poletti, Giovanni, Rosique, Javier, Bortolini, Maria Cátira, Canizales Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Ruiz Linares, Andres, and Gonzalez Jose, Rolando

Subjects
purl.org/pe-repo/ocde/ford#5.04.03 [https], principal component analysis, very elderly, Hispanic, human experiment, Genética y Herencia, América Latina, environmental factor, middle aged, genetics, Aged, 80 and over, Principal Component Analysis, Ancestralidade, anthropometry, Anthropometry, adult, craniofacial morphology, Hispanic or Latino, Middle Aged, genetic ancestry, aged, female, purl.org/pe-repo/ocde/ford#3.01.01 [https], ancestry group, young adult, genetic marker, Hispanic Americans, CIENCIAS NATURALES Y EXACTAS, Assimetria facial, Adult, analysis of variance, Adolescent, heredity, Article, Ciencias Biológicas, Young Adult, socioeconomics, male, Humans, heterozygosity, human, normal human, geometric morphometrics, Aged, Analysis of Variance, fluctuating asymmetry, face, Central America, South America, face asymmetry, facial fluctuating asymmetry, Latin America, Facial Asymmetry, Face, pathology, facial directional asymmetry, anatomy and histology
Abstract

Fluctuating and directional asymmetry are aspects of morphological variation widely used to infer environmental and genetic factors affecting facial phenotypes. However, the genetic basis and environmental determinants of both asymmetry types is far from being completely known. The analysis of facial asymmetries in admixed individuals can be of help to characterize the impact of a genome's heterozygosity on the developmental basis of both fluctuating and directional asymmetries. Here we characterize the association between genetic ancestry and individual asymmetry on a sample of Latin-American admixed populations. To do so, three-dimensional (3D) facial shape attributes were explored on a sample of 4,104 volunteers aged between 18 and 85 years. Individual ancestry and heterozygosity was estimated using more than 730,000 genome-wide markers. Multivariate techniques applied to geometric morphometric data were used to evaluate the magnitude and significance of directional and fluctuating asymmetry (FA), as well as correlations and multiple regressions aimed to estimate the relationship between facial FA scores and heterozygosity and a set of covariates. Results indicate that directional and FA are both significant, the former being the strongest expression of asymmetry in this sample. In addition, our analyses suggest that there are some specific patterns of facial asymmetries characterizing the different ancestry groups. Finally, we find that more heterozygous individuals exhibit lower levels of asymmetry. Our results highlight the importance of including ancestry-admixture estimators, especially when the analyses are aimed to compare levels of asymmetries on groups differing on socioeconomic levels, as a proxy to estimate developmental noise. Fil: Quinto Sanchez, Mirsha Emmanuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Adhikari, Kaustubh. University College London; Estados Unidos Fil: Acuña Alonzo, Victor. University College London; Estados Unidos. Instituto Nacional de Antropología E Historia; México Fil: Cintas, Celia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Silva de Cerqueira, Caio Cesar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Ramallo, Virginia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Castillo, Lucía Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico; Argentina Fil: Farrera, Arodi. Universidad Nacional Autónoma de México; México Fil: Jaramillo, Claudia. Universidad de Antioquia; Colombia Fil: Williams Arias. Universidad de Antioquia; Colombia Fil: Fuentes, Macarena. Universidad de Tarapacá; Chile Fil: Everardo, Paola. Instituto Nacional de Antropología E Historia; México Fil: de Avila, Francisco. Instituto Nacional de Antropología E Historia; México Fil: Gomez Valdés, Jorge. Universidad Nacional Autónoma de México; México Fil: Hünemeier, Tábita. Universidade Federal do Rio Grande do Sul; Brasil Fil: Gibbon, Shara. University College London; Estados Unidos Fil: Gallo, Carla. Universidad Peruana Cayetano Heredia; Perú Fil: Poletti, Giovanni. Universidad Peruana Cayetano Heredia; Perú Fil: Rosique, Javier. Universidad de Antioquia; Colombia Fil: Bortolini, Maria Cátira. Universidade Federal do Rio Grande do Sul; Brasil Fil: Canizales Quinteros, Samuel. Universidad Nacional Autónoma de México; México Fil: Rothhammer, Francisco. Universidad de Tarapacá; Chile Fil: Bedoya, Gabriel. Universidad de Antioquia; Colombia Fil: Ruiz Linares, Andres. University College London; Estados Unidos Fil: Gonzalez Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Nacional Patagónico; Argentina

Published
2015

12. Admixture in Latin America: geographic structure, phenotypic diversity and self-perception of ancestry based on 7,342 individuals

Author

Ruiz-Linares, Andrés, Adhikari, Kaustubh, Acuña-Alonzo, Victor, Quinto-Sanchez, Mirsha, Jaramillo, Claudia, Arias, William, Fuentes, Macarena, Pizarro, María, Everardo, Paola, de Avila, Francisco, Gómez-Valdés, Jorge, León-Mimila, Paola, Hunemeier, Tábita, Ramallo, Virginia, Silva de Cerqueira, Caio C., Burley, Mari-Wyn, Konca, Esra, de Oliveira, Marcelo Zagonel, Veronez, Mauricio Roberto, Rubio-Codina, Marta, Attanasio, Orazio, Gibbon, Sahra, Ray, Nicolas, Gallo, Carla, Poletti, Giovanni, Rosique, Javier, Schuler-Faccini, Lavinia, Salzano, Francisco M., Bortolini, Maria-Cátira, Canizales-Quinteros, Samuel, Rothhammer, Francisco, Bedoya, Gabriel, Balding, David, and Gonzalez-José, Rolando

Subjects
Male, lcsh:QH426-470, purl.org/pe-repo/ocde/ford#1.06.03 [https], Ethnic Groups/genetics, Diversidad genética humana, Quantitative Trait, Heritable, América Latina, Ethnicity, Genetics, Humans, ddc:333.7-333.9, Diversidad, Geography, Genetic Variation, Biology and Life Sciences, Human Genetics, Biological Evolution, Self Concept, lcsh:Genetics, Genetics, Population, Latin America, Phenotype, Female, América Latina - Geografía, Fenotipo, purl.org/pe-repo/ocde/ford#1.06.07 [https], Research Article
Abstract

The current genetic makeup of Latin America has been shaped by a history of extensive admixture between Africans, Europeans and Native Americans, a process taking place within the context of extensive geographic and social stratification. We estimated individual ancestry proportions in a sample of 7,342 subjects ascertained in five countries (Brazil, Chile, Colombia, México and Perú). These individuals were also characterized for a range of physical appearance traits and for self-perception of ancestry. The geographic distribution of admixture proportions in this sample reveals extensive population structure, illustrating the continuing impact of demographic history on the genetic diversity of Latin America. Significant ancestry effects were detected for most phenotypes studied. However, ancestry generally explains only a modest proportion of total phenotypic variation. Genetically estimated and self-perceived ancestry correlate significantly, but certain physical attributes have a strong impact on self-perception and bias self-perception of ancestry relative to genetically estimated ancestry., Author Summary Latin America has a history of extensive mixing between Native Americans and people arriving from Europe and Africa. As a result, individuals in the region have a highly heterogeneous genetic background and show great variation in physical appearance. Latin America offers an excellent opportunity to examine the genetic basis of the differentiation in physical appearance between Africans, Europeans and Native Americans. The region is also an advantageous setting in which to examine the interplay of genetic, physical and social factors in relation to ethnic/racial self-perception. Here we present the most extensive analysis of genetic ancestry, physical diversity and self-perception of ancestry yet conducted in Latin America. We find significant geographic variation in ancestry across the region, this variation being consistent with demographic history and census information. We show that genetic ancestry impacts many aspects of physical appearance. We observe that self-perception is highly influenced by physical appearance, and that variation in physical appearance biases self-perception of ancestry relative to genetically estimated ancestry.

Published
2013

13. Genetics of schizophrenia: A consensus paper of the WFSBP Task Force on Genetics

Author

Carla Gallo, Jorge Ospina-Duque, David A. Collier, Michael Gill, Yongyong Shi, James L. Kennedy, Ladislav Hosák, Alejo Corrales, Florence Thibaut, Lynn E. DeLisi, Ina Giegling, David St Clair, Frank Bellivier, Alessandro Serretti, Julien Mendlewicz, Wolfgang Maier, Miguel Marquez, Marion Leboyer, Michael Conlon O'Donovan, Markus M. Nöthen, Michael John Owen, Stephan Claes, Ole Mors, Isabelle Massat, Sven Cichon, Dan Rujescu, Peter Propping, Rainald Mössner, Pierandrea Muglia, Giegling, Ina, Hosak, Ladislav, Mössner, Rainald, Serretti, Alessandro, Bellivier, Frank, Claes, Stephan, Collier, David A., Corrales, Alejo, Delisi, Lynn E., Gallo, Carla, Gill, Michael, Kennedy, James L., Leboyer, Marion, Maier, Wolfgang, Miguel, Marquez, Massat, Isabelle, Mors, Ole, Muglia, Pierandrea, Nöthen, Markus M., Ospina-Duque, Jorge, Owen, Michael J., Propping, Peter, Shi, Yongyong, St Clair, David, Thibaut, Florence, Cichon, Sven, Mendlewicz, Julien, O'Donovan, Michael C., and Rujescu, Dan

Subjects
0301 basic medicine, medicine.medical_specialty, Psychosis, Consensus, Schizophrenia (object-oriented programming), Population, polygenic, Disease, Biology, psychosi, 03 medical and health sciences, 0302 clinical medicine, Genetic, Journal Article, medicine, Humans, Psychiatry, education, genome, Biological Psychiatry, Psychiatric genetics, Genetic association, Genetics, education.field_of_study, Task force, Inheritance (genetic algorithm), sequencing, medicine.disease, psychiatry, schizophrenia, Psychiatry and Mental health, 030104 developmental biology, 030217 neurology & neurosurgery
Abstract

OBJECTIVES: Schizophrenia is a severe psychiatric disease affecting about 1% of the general population. The relative contribution of genetic factors has been estimated to be up to 80%. The mode of inheritance is complex, non-Mendelian, and in most cases involving the combined action of large numbers of genes.METHODS: This review summarises recent efforts to identify genetic variants associated with schizophrenia detected, e.g., through genome-wide association studies, studies on copy-number variants or next-generation sequencing.RESULTS: A large, new body of evidence on genetics of schizophrenia has accumulated over recent years. Many new robustly associated genetic loci have been detected. Furthermore, there is consensus that at least a dozen microdeletions and microduplications contribute to the disease. Genetic overlap between schizophrenia, other psychiatric disorders, and neurodevelopmental syndromes raised new questions regarding the current classification of psychiatric and neurodevelopmental diseases.CONCLUSIONS: Future studies will address especially the functional characterisation of genetic variants. This will hopefully open the doors to our understanding of the pathophysiology of schizophrenia and other related diseases. Complementary, integrated systems biology approaches to genomics, transcriptomics, proteomics and metabolomics may also play crucial roles in enabling a precision medicine approach to the treatment of individual patients.

Published
2017
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14. Consensus paper of the WFSBP Task Force on Genetics: Genetics, epigenetics and gene expression markers of major depressive disorder and antidepressant response

Author

Florence Thibaut, Ladislav Hosák, David A. Collier, Lynn Le Delisi, Alejo Corrales, Rainald Mössner, Jorge Ospina-Duque, Stephan Claes, David St Clair, Michael Conlon O'Donovan, Markus M. Nöthen, Frank Bellivier, Carla Gallo, Amanda Lisoway, Alessandro Serretti, Isabelle Massat, Julien Mendlewicz, James Jl Kennedy, Laura Mandelli, Marion Leboyer, Ole Mors, Sven Cichon, Dan Rujescu, Yongyong Shi, Wolfgang Maier, Ina Giegling, Chiara Fabbri, Manuel Marquez, Pierandrea Muglia, Michael Gill, Peter Propping, Fabbri, Chiara, Hosak, Ladislav, Mössner, Rainald, Giegling, Ina, Mandelli, Laura, Bellivier, Frank, Claes, Stephan, Collier, David A., Corrales, Alejo, Delisi, Lynn E., Gallo, Carla, Gill, Michael, Kennedy, James L., Leboyer, Marion, Lisoway, Amanda, Maier, Wolfgang, Marquez, Miguel, Massat, Isabelle, Mors, Ole, Muglia, Pierandrea, Nöthen, Markus M., O’Donovan, Michael C., Ospina-Duque, Jorge, Propping, Peter, Shi, Yongyong, St Clair, David, Thibaut, Florence, Cichon, Sven, Mendlewicz, Julien, Rujescu, Dan, and Serretti, Alessandro

Subjects
Genetic Markers, Consensus, Disease, Pharmacology, Biology, Bioinformatics, transcriptomics-proteomic, Epigenesis, Genetic, genetics-epigenetic, 03 medical and health sciences, 0302 clinical medicine, Journal Article, medicine, Major depression, Humans, Epigenetics, Pathological, Biological Psychiatry, Randomized Controlled Trials as Topic, Depressive Disorder, Major, antidepressant, Neuronal Plasticity, medicine.disease, Antidepressive Agents, 030227 psychiatry, Psychiatry and Mental health, Major depressive disorder, Antidepressant, FKBP5, Transcriptome, 030217 neurology & neurosurgery, Glucocorticoid, Pharmacogenetics, medicine.drug
Abstract

Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels. Polymorphisms in genes involved in antidepressant metabolism (cytochrome P450 isoenzymes), antidepressant transport (ABCB1), glucocorticoid signalling (FKBP5) and serotonin neurotransmission (SLC6A4 and HTR2A) were among those included in the first pharmacogenetic assays that have been tested for clinical applicability. The results of these investigations were encouraging when examining patient-outcome improvement. Furthermore, a nine-serum biomarker panel (including BDNF, cortisol and soluble TNF-α receptor type II) showed good sensitivity and specificity in differentiating between MDD and healthy controls. These first diagnostic and response-predictive tests for MDD provided a source of optimism for future clinical applications. However, such findings should be considered very carefully because their benefit/cost ratio and clinical indications were not clearly demonstrated. Future tests may include combinations of different types of biomarkers and be specific for MDD subtypes or pathological dimensions.

Published
2016
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