No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest

Estimation of Genetic Correlation via Linkage Disequilibrium Score Regression and Genomic Restricted Maximum Likelihood

J. Lönnqvist on työryhmän Psychiat Genomics Consortium jäsen.Genetic correlation is a key population parameter that describes the shared genetic architecture of complex traits and diseases. It can be estimated by current state-of-art methods, i.e., linkage disequilibrium score regression (LDSC) and genomic restricted maximum likelihood (GREML). The massively reduced computing burden of LDSC compared to GREML makes it an attractive tool, although the accuracy (i.e., magnitude of standard errors) of LDSC estimates has not been thoroughly studied. In simulation, we show that the accuracy of GREML is generally higher than that of LDSC. When there is genetic heterogeneity between the actual sample and reference data from which LD scores are estimated, the accuracy of LDSC decreases further. In real data analyses estimating the genetic correlation between schizophrenia (SCZ) and body mass index, we show that GREML estimates based on similar to 150,000 individuals give a higher accuracy than LDSC estimates based on similar to 400,000 individuals (from combinedmeta-data). A GREML genomic partitioning analysis reveals that the genetic correlation between SCZ and height is significantly negative for regulatory regions, which whole genome or LDSC approach has less power to detect. We conclude that LDSC estimates should be carefully interpreted as there can be uncertainty about homogeneity among combined meta-datasets. We suggest that any interesting findings from massive LDSC analysis for a large number of complex traits should be followed up, where possible, with more detailed analyses with GREML methods, even if sample sizes are lesser.Peer reviewe

Herança da resistência de milho a Pratylenchus spp. Inheritance of corn resistance to Pratylenchus spp.

As espécies de nematóides que mais causam problemas na cultura do milho no Brasil são Pratylenchus zeae e P. brachyurus. O uso de variedades resistentes é o método ideal de controle, sendo que já foram identificadas fontes de resistência em alguns genótipos de milho. Utilizou-se a linhagem Col 2(22), considerada como resistente, e a Ip 48-5-3, como suscetível, mais as gerações F1, F2 e retrocruzamentos com o objetivo de obter informações sobre a herança da resistência. Avaliaram-se esses genótipos em campo, em área infestada por P. zeae (76%) e P. brachyurus (24%), em Pindorama. Plantou-se o experimento em janeiro de 1986 e, após oitenta dias, coletaram-se amostras de raízes dos tratamentos para avaliação do número de nematóides por grama de raiz. Os resultados mostraram que a diferença observada quanto à resistência entre as linhagens Col 2(22) e Ip 48-5-3 é, provavelmente, devida a dois pares de genes dominantes de efeitos genéticos aditivos. As herdabilidades no sentido amplo e restrito foram altas, respectivamente 82,0 e 80,8%.<br>The species Pratylenchus zeae and P. brachyurus are the most important nematodes in Brazilian corn fields. Their control with systemic nematicides is efficient but frequently not economic. Previous work indicated that resistance to these nematodes could be found in some corn genotypes. The inheritance of corn resistance to the nematodes was studied using lines of Col 2(22) (resistant) and Ip 48-5-3 (susceptible), the generations F1, F2 and backcrosses. The genotypes were sowed in a field infested with P. zeae (76%) and P. brachyurus (24%). The experiment was carried out at the Pindorama Experimental Station, State of São Paulo, Brazil, in January of 1986. Eighty days after planting the number of nematodes per gram of roots was determined. The results indicated that the resistance to this pest for the line Col 2(22) was due to two dominant genes with additive effect. The heritability was high in broad and narrow sense being respectively 82.0% and 80.8%

Genética da tolerância ao alumínio em milho Cateto Genetics of aluminum tolerance in maize Cateto

Tem-se observado alta tolerância ao alumínio em milho Cateto. Devido à importância dessa característica nos híbridos comerciais e à divergência das informações disponíveis sobre a herança desse caráter, estudou-se a genética da tolerância ao alumínio nas linhagens lp 48-5-3 (Cateto) e Col (22) (duro da Colômbia), e gerações F1, F2 e retrocruzamentos. Estes genótipos foram avaliados em solução nutritiva com 4,5 ppm de alumínio, em dois experimentos conduzidos em Campinas, em 1985. A característica de raiz mais adequada para o estudo foi o crescimento líquido da radícula (CLR). A distribuição de freqüência da geração F2 foi contínua e unimodal, apresentando apenas classes do F1 e do pai tolerante. Deve-se a alta tolerância ao alumínio da linhagem lp 48-5-3, principalmente, à ação de genes menores, de efeitos genéticos aditivos. A herdabilidade no sentido amplo e restrito foi alta, indicando que a seleção de genótipos tolerantes na geração F2 é eficiente.<br>Maize Cateto inbred line has shown high aluminum tolerance. Due to the importance of this trait in commercial hybrids as well as the lack of consistent informations about the inheritance mechanism involved, the genetics of aluminum tolerance in one maize Cateto inbred line was studied. The inbred lines lp 48-5-3 (Cateto), Col 2(22) (flint from Colombia) and the F1, F2 and backcrosses generations were used. Two replicated experiments were carried ou at Campinas, State of São Paulo, Brazil, in 1985, to evaluate these genotypes grown in nutrient solutions containing 4.5 ppm of Al. Radicle net growth (CLR) was the most adequate measurement to distinguish maize genotypes for Al tolerance. The F2 frequency distribution was continuous, unimodal and yielded only classes resembling those of the F1 and the tolerant parent. The high Al tolerance of the maize inbred line lp 48-5-3 was due to the action of additive minor genes. Both broad and narrow sense heritabilities were high, indicating that plant selection in F2 generation for Al tolerance is efficient

Seleção efetiva para o caráter número de afilhos em populações segregantes de trigo Selection eficiency for tillerning in segregating wheat populations

O ganho genético obtido com a seleção em gerações segregantes é dependente do cruzamento, das condições experimentais e do caráter alvo de seleção. O objetivo deste trabalho foi determinar o ganho com a seleção em planta espaçada, na geraç��o F2 para número de afilhos, utilizando diferentes critérios de seleção, além de verificar a efetividade destas seleções na geração subseqüente, nos métodos de semeadura deplanta espaçada e linha cheia. As gerações segregantes foram desenvolvidos em 2006 (F2) e 2007 (F2 e F3), sendo a geração F3 avaliada em planta espaçada e linha cheia. Foram empregados três critérios de seleção: a) elevado número de afilhos e alta produção de grãos; b) reduzido número de afilhos com elevada produção de grãos e c) bulk da população. Foram testadas 15 combinações envolvendo genitores com diferente potencial de afilhamento. Os resultados indicam que mesmo em reduzida magnitude, as estimativas de herdabilidade para estimar a média da próxima geração, revelaram eficiência, porém, somente quando as gerações utilizadas foram desenvolvidas em iguais condições de ambiente e manejo. A seleção para elevado ou reduzido número de afilhos e em bulk, foram dependentes do sistema de manejo em que a população segregante tenha sido submetida. A seleção para elevado número de afilhos revelou o maior ganho genético para produção de grãos, porém, a efetividade da seleção em planta espaçada não proporcionou o mesmo comportamento em competição. O melhor desempenho em rendimento de grãos foi detectado na seleção para reduzido número de afilhos, com média elevada para massa de grãos em competição.<br>The genetic gain obtained with the selection in segregating generations depends on the cross, experimental conditions and the target trait selected. The objective of this work was to determine the genetic gain with selection in spaced plants, in the F2 generation for the character number of tillers, using different selection criteria. In addition it aimed at to verify the effectiveness of these selections by looking at next generations of plants selected by the spaced plant and full row methods. The segregating generations were conducted in the years 2006 (F2) and 2007 (F2 and F3), being the F3 generation evaluated as spaced plant and full row. Three selection criteria were used: i) high tiller number and grain production; ii) low tiller number with high grain production and iii) a bulk of 15 parental genotypes with different tillering potential. The results pointed out that heritability estimates were efficient for the prediction of next generation means when the generations used were under the same environmental and management conditions. The efficiency of the selection for high or low tillering ability and the bulk selection were dependent of the crop management system used. The selection for high tiller number was associated to a higher genetic gain for grain production. However, the efficiency of the selection was different when spaced and competing plants are compared. The best performance for grain yield was achieved selecting for low tiller number in competing plants, resulted in higher total grain weight