Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study.

Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n = 789) and Northern and Western European (NWE, N = 2,280) origin. A whole genome association (WGA) analysis (500K Affymetrix platform) was carried out in a set of unrelated NWE subjects consisting of approximately 1,000 subjects with dyslipidemia and 1,000 overweight subjects with normal lipids. Peak evidence for linkage occurred at chromosome 8p23 in NWE subjects (lod = 3.10) and at chromosome 3q28 near ADIPOQ, the adiponectin structural gene, in TSE subjects (lod = 1.70). In the WGA analysis, the single-nucleotide polymorphisms (SNPs) most strongly associated with adiponectin were rs3774261 and rs6773957 (P < 10(-7)). These two SNPs were in high linkage disequilibrium (r(2) = 0.98) and located within ADIPOQ. Interestingly, our fourth strongest region of association (P < 2 x 10(-5)) was to an SNP within CDH13, whose protein product is a newly identified receptor for high-molecular-weight species of adiponectin. Through WGA analysis, we confirmed previous studies showing SNPs within ADIPOQ to be strongly associated with variation in adiponectin levels and further observed these to have the strongest effects on adiponectin levels throughout the genome. We additionally identified a second gene (CDH13) possibly influencing variation in adiponectin levels. The impact of these SNPs on health and disease has yet to be determined.

Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection.

Polymorphisms in IL28B were shown to affect clearance of hepatitis C virus (HCV) infection in genome-wide association (GWA) studies. Only a fraction of patients with chronic HCV infection develop liver fibrosis, a process that might also be affected by genetic factors. We performed a 2-stage GWA study of liver fibrosis progression related to HCV infection. We studied well-characterized HCV-infected patients of European descent who underwent liver biopsies before treatment. We defined various liver fibrosis phenotypes on the basis of METAVIR scores, with and without taking the duration of HCV infection into account. Our GWA analyses were conducted on a filtered primary cohort of 1161 patients using 780,650 single nucleotide polymorphisms (SNPs). We genotyped 96 SNPs with P values <5 × 10(-5) from an independent replication cohort of 962 patients. We then assessed the most interesting replicated SNPs using DNA samples collected from 219 patients who participated in separate GWA studies of HCV clearance. In the combined cohort of 2342 HCV-infected patients, the SNPs rs16851720 (in the total sample) and rs4374383 (in patients who received blood transfusions) were associated with fibrosis progression (P(combined) = 8.9 × 10(-9) and 1.1 × 10(-9), respectively). The SNP rs16851720 is located within RNF7, which encodes an antioxidant that protects against apoptosis. The SNP rs4374383, together with another replicated SNP, rs9380516 (P(combined) = 5.4 × 10(-7)), were linked to the functionally related genes MERTK and TULP1, which encode factors involved in phagocytosis of apoptotic cells by macrophages. Our GWA study identified several susceptibility loci for HCV-induced liver fibrosis; these were linked to genes that regulate apoptosis. Apoptotic control might therefore be involved in liver fibrosis.

Genes mirror geography within Europe.

Understanding the genetic structure of human populations is of fundamental interest to medical, forensic and anthropological sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation and suggest the potential to use large samples to uncover variation among closely spaced populations. Here we characterize genetic variation in a sample of 3,000 European individuals genotyped at over half a million variable DNA sites in the human genome. Despite low average levels of genetic differentiation among Europeans, we find a close correspondence between genetic and geographic distances; indeed, a geographical map of Europe arises naturally as an efficient two-dimensional summary of genetic variation in Europeans. The results emphasize that when mapping the genetic basis of a disease phenotype, spurious associations can arise if genetic structure is not properly accounted for. In addition, the results are relevant to the prospects of genetic ancestry testing; an individual's DNA can be used to infer their geographic origin with surprising accuracy-often to within a few hundred kilometres.

Biomasa, distribución y concentración de los principales recursos pelágicos. Crucero 9502-04 BIC NSP-1 9502 (13 febrero - 05 abril, 1995)

Presenta los estimados de biomasa, distribución delos principales recursos pelágicos: anchoveta, sardina, jurel y caballa existentes en el Perú y se determina así mismo el grado de mezcla de estos recursos a partir de los lances de comprobación y la interrelación recurso/ambiente.

Aspectos hidroquímicos del mar peruano. Crucero de evaluación de recursos pelágicos 9502- 04 BIC /NSP-1 (13 febrero - 05 abril, 1995)

Da a conocer la distribución superficial y de profundidad hasta 200 m. de las sales nutritivas, que conjuntamente al oxigeno disuelto y clorofila "a" tiene enorme importancia desde el punto de vista biológico, por ser elementos fundamentales en la síntesis orgánica del agua de mar.

Características del zooplancton e ictioplancton durante el periodo de verano 1995 frente a la costa peruana (13 febrero - 05 abril, 1995)

Presenta características del zooplancton e ictiopancton frente a la costa peruana, encontradas durante el crucero de Evaluación de los recursos pelágicos abordo del BIC SNP-1 llevado a cabo del 13 de febrero al 05 de abril, así como la distribución y concentración de huevos y larvas de los recursos anchoveta y sardina.

Crucero de evaluación de la biomasa desovante de la anchoveta peruana, 1995. Actividades, resultados y perspectivas

Con el propósito de estimar la biomasa desovante de las especies anchoveta peruana (Engraulis ringens J.) y sardina (Sardinops sagax sagax J.), se ejecutó el Crucero 9508-09 a bordo del BIC Humboldt y del SNP-1, del 12 de agosto al 22 de setiembre de 1995, cubriendo el área entre Tambo de Mora (13°30 'S) y Paita (5°S). Se obtuvo los cinco parámetros que el Método de Producción de Huevos (MPH) requiere para estimar la biomasa de la población desovante de la anchoveta. Además se consideró cuatro perfiles para investigar las variables oceanográficas: Callao (12° S) y Chimbote (9°10 'S) hasta las 100 millas y Punta Falsa (6°S) y Paita hasta 150 millas de la costa. La biomasa desovante de la anchoveta estimada por el MPH entre Tambo de Mora y Punta Falsa en agosto y setiembre de 1995, fue calculada en 5,9 millones de toneladas, con una producción diaria de huevos de 19,1 E+13 y una frecuencia de desove de 0,12. La anchoveta estuvo localizada cerca de la costa entre Callao y Chimbote, mientras que de Salaverry (8°13 'S) a Punta Falsa, su distribución se amplió, alcanzando hasta las 60 millas fuera de la costa. No se pudo estimar la biomasa desovante de la sardina debido a la dispersión de este recurso. Durante el desarrollo del crucero, las condiciones oceanográficas se encontraron dentro de la normalizada para la época, con afloramientos intensos en la franja costera y con advección de aguas tropicales superficiales de Chancay (11°35 'S) a Casma (9°27 'S).

Frecuencia de desove de la anchoveta peruana, engraulis ringens, en agosto y setiembre 1995

Se estimó la frecuencia de desove (F) de la anchoveta peruana Engraulis ringens, colectada en el área Tambo de Mora a Paita, en el Crucero BIC Humboldt y BIC SNP-1 9508-09. El valor de la frecuencia de desove fue de 0,119 (11,9%) con una varianza (V) de 0,00046 y un coeficiente de variación (CV) de 0,180402. Es decir que en el período de muestreo de 28 días una hembra promedio desovó 3,3 veces, o cada 8 días. Se calculó los valores de F por grado latitudinal y se discutió su relación con la temperatura superficial del mar.

Ictioplancton entre Tambo de Mora y Punta Falsa durante agosto y setiembre de 1995

Se presentan los resultados sobre la composición, distribución y concentración de huevos y larvas de peces durante el Crucero BIC Humboldt y BIC SNP-1 9508-09, llevado a cabo entre el 12 de agosto y 22 de setiembre de 1995 entre Tambo de Mora (13°30 'S) y Punta Falsa (06° S). Se determinó larvas de 12 familias. Fue posible identificar 11 géneros y 9 especies. Los huevos y las larvas de anchoveta se distribuyeron en toda el área explorada. La sardina tuvo una pequeña concentración en la zona norte.