Complex Traits

Assortative mating, or the tendency for individuals with similar phenotypes to mate more frequently than expected by chance, has been reported for a variety of complex traits, including many neuropsychiatric disorders. Although assortative mating has been reported in affective disorders, the studies done to date have been inconclusive. This study attempts to assess the degree of assortative mating in individuals

Morphological integration refers to the modular structuring of inter-trait relationships in an organism, which could bias the direction and rate of morphological change, either constraining or facilitating evolution along certain dimensions of the morphospace. Therefore, the description of patterns and magnitudes of morphological integration and the analysis of their evolutionary consequences are central to understand the evolution of complex traits. Here we analyze morphological integration in the skull of several mammalian orders, addressing the following questions: are there common patterns of inter-trait relationships? Are these patterns compatible with hypotheses based on shared development and function? Do morphological integration patterns and magnitudes vary in the same way across groups? We digitized more than 3,500 specimens spanning 15 mammalian orders, estimated the correspondent pooled within-group correlation and variance/covariance matrices for 35 skull traits and compared those matrices among the orders. We also compared observed patterns of integration to theoretical expectations based on common development and function. Our results point to a largely shared pattern of inter-trait correlations, implying that mammalian skull diversity has been produced upon a common covariance structure that remained similar for at least 65 million years. Comparisons with a rodent genetic variance/covariance matrix suggest that this broad similarity extends also to the genetic factors underlying phenotypic variation. In contrast to the relative constancy of inter-trait correlation/covariance patterns, magnitudes varied markedly across groups. Several morphological modules hypothesized from shared development and function were detected in the mammalian taxa studied. Our data provide evidence that mammalian skull evolution can be viewed as a history of inter-module parcellation, with the modules themselves being more clearly marked in those lineages with lower overall magnitude of integration. The implication of these findings is that the main evolutionary trend in the mammalian skull was one of decreasing the constraints to evolution by promoting a more modular architecture.

We develop a Bayesian mixed linear model that simultaneously estimates single-nucleotide polymorphism (SNP)-based heritability, polygenicity (proportion of SNPs with nonzero effects), and the relationship between SNP effect size and minor allele frequency for complex traits in conventionally unrelated individuals using genome-wide SNP data. We apply the method to 28 complex traits in the UK Biobank data (N = 126,752) and show that on average, 6% of SNPs have nonzero effects, which in total explain 22% of phenotypic variance. We detect significant (P < 0.05/28) signatures of natural selection in the genetic architecture of 23 traits, including reproductive, cardiovascular, and anthropometric traits, as well as educational attainment. The significant estimates of the relationship between effect size and minor allele frequency in complex traits are consistent with a model of negative (or purifying) selection, as confirmed by forward simulation. We conclude that negative selection acts pervasively on the genetic variants associated with human complex traits.

Grain yield is a complex trait, strongly influenced by the environment: severe losses can be caused by drought, a stress common in most maize-growing areas, including temperate climatic zones. Accordingly, drought tolerance is one of the main components of yield stability, and its improvement is a major challenge to breeders. The aim of the present work was the identification, in maize genotypes adapted to temperate areas, of genomic segments responsible for the expression of drought tolerance of yield components: ear length, ear weight, kernel weight, kernel number and 50-kernel weight. A linkage analysis between the expression of these traits and molecular markers was performed on a recombinant inbred population of 142 families, obtained by repeated selfing of the F1 between lines B73 and H99. The population, genotyped at 173 loci (RFLPs, microsatellites and AFLPs), was evaluated in well-watered and water-stressed conditions. A drought tolerance index was calculated as the ratio between the mean value of the trait in the two environments. For the traits measured, a highly positive correlation was found over the two water regimes, and more than 50% of the quantitative trait loci (QTLs) detected were the same in both; moreover, the direction of the allelic contribution was always consistent, the allele increasing the trait value being mostly from line B73. Several QTLs were common to two or more traits. For the tolerance index, however, most of the QTLs were specific for a single component and different from those controlling the basic traits; in addition, a large proportion of the alleles increasing tolerance were provided by line H99. The data suggest that drought tolerance for yield components is largely associated with genetic and physiological factors independent from those determining the traits per se. The implications of these results for developing an efficient strategy of marker-assisted selection for drought tolerance are discussed.

To understand the genetic epidemiology of obesity and cancer means to consider the genetics of not only these two complex diseases but also the many risk factors associated with them and the molecular mechanisms likely to contribute to their underlying etiology. It is therefore the purpose of this chapter to highlight the following: genetic mapping studies that have been done to isolate genes related to obesity, genetic studies aimed to identify genes for obesity risk factors, and, finally, a discussion of the genes shared across or among the studies of obesity and/or its risk factors and the various cancers. This is by no means an exhaustive discussion as these are each complex traits with complex molecular mechanisms. It is, however, intended to be an overview of the genes likely to be involved in the cascade of pathways linking obesity and cancer. It is well known that obesity continues to be a leading public health concern not only in the United States but now worldwide. From 1980 to 2002, the prevalence of obesity doubled in adults aged over 20 and overweight prevalence tripled in children and adolescents aged 6–9 years. The estimates of overweight and obesity in 2003–2004 showed that 17.1% of US children and adolescents were overweight and 32.2% of adults were obese [143]. The increasing rates of obesity among children are especially alarming and suggest continuing increases in the rates of obesity-related cancers. Since being overweight in childhood predicts obesity in adulthood [208], obesity occurring in childhood may operate as a ‘cumulative’ exposure that influences cancer risk in later life. Obese children may be subject to potentially long periods of hormonal exposures that operate during adolescence to influence propensity to neoplastic diseases. In females, childhood obesity may also affect the levels of sex hormone at adolescence. A prospective study of 55-year follow-up on 508 adolescents at 13–18 years from Harvard Growth Study showed that overweight adolescent boys had a nine-fold increased risk of colorectal cancer mortality [161]. Associations between adolescent weight and cancer persisted even after adjusting for adult BMI. A 50-year follow-up of >2,000 British children showed an overall 9% increase in cancer incidence per standard deviation increase in BMI, with effects three times larger for smoking-related cancers. There is also evidence from an Israeli case–control study which indicated that being in the upper quartile of BMI at age 18 years was associated with a 42% increase for ovarian cancer [24]. However, the mechanisms underlying the association between childhood obesity and cancer are not well understood, particularly in conjunction with genetic data. In one case–control study of 40 obese and 40 non-obese prepubertal children, the obese group showed higher levels of IGF-1, insulin, and lower sex-binding hormone than that of the non-obese group [182]. This suggests that high levels of growth factors and altered sex hormone profiles are present in obese children and the exposures to an adverse metabolic milieu may begin early in life.

Androgenic responses of 10 F1 wheat hybrids and 13 parental genotypes were studied. It was observed that the studied androgenic traits (androgenic capacity, callus yield, and frequency of green plants) were genotype dependent. On average for all genotypes, 10.6% of the anthers were responsive and 12.2 calluses were produced per 100 anthers. Line 9D-27-262 and the hybrid 9D-27-262/Posavka-2, had the highest frequencies of green plants, 11% and 12% respectively. It was found that 30.4% of the genotypes produced 2 or more green plants per 100 anthers, which can be considered as sufficient number for use in breeding. Heterotic effects as well as additive and dominant gene actions were found to control the inheritance of all characters.

The success of genome-wide association (GWA) studies for the detection of sequence variation affecting complex traits in human has spurred interest in the use of large-scale high-density single nucleotide polymorphism (SNP) genotyping for the identification of quantitative trait loci (QTL) and for marker-assisted selection in model and agricultural species. A cost-effective and efficient approach for the development of a custom genotyping assay interrogating 54,001 SNP loci to support GWA applications in cattle is described. A novel algorithm for achieving a compressed inter-marker interval distribution proved remarkably successful, with median interval of 37 kb and maximum predicted gap of &lt;350 kb. The assay was tested on a panel of 576 animals from 21 cattle breeds and six outgroup species and revealed that from 39,765 to 46,492 SNP are polymorphic within individual breeds (average minor allele frequency (MAF) ranging from 0.24 to 0.27). The assay also identified 79 putative co...