Estimating indirect parental genetic effects on offspring phenotypes using virtual parental genotypes derived from sibling and half sibling pairs.

Indirect parental genetic effects may be defined as the influence of parental genotypes on offspring phenotypes over and above that which results from the transmission of genes from parents to their children. However, given the relative paucity of large-scale family-based cohorts around the world, it is difficult to demonstrate parental genetic effects on human traits, particularly at individual loci. In this manuscript, we illustrate how parental genetic effects on offspring phenotypes, including late onset conditions, can be estimated at individual loci in principle using large-scale genome-wide association study (GWAS) data, even in the absence of parental genotypes. Our strategy involves creating "virtual" mothers and fathers by estimating the genotypic dosages of parental genotypes using physically genotyped data from relative pairs. We then utilize the expected dosages of the parents, and the actual genotypes of the offspring relative pairs, to perform conditional genetic association analyses to obtain asymptotically unbiased estimates of maternal, paternal and offspring genetic effects. We apply our approach to 19066 sibling pairs from the UK Biobank and show that a polygenic score consisting of imputed parental educational attainment SNP dosages is strongly related to offspring educational attainment even after correcting for offspring genotype at the same loci. We develop a freely available web application that quantifies the power of our approach using closed form asymptotic solutions. We implement our methods in a user-friendly software package IMPISH (IMputing Parental genotypes In Siblings and Half Siblings) which allows users to quickly and efficiently impute parental genotypes across the genome in large genome-wide datasets, and then use these estimated dosages in downstream linear mixed model association analyses. We conclude that imputing parental genotypes from relative pairs may provide a useful adjunct to existing large-scale genetic studies of parents and their offspring.

Modeling Parent-Specific Genetic Nurture in Families with Missing Parental Genotypes: Application to Birthweight and BMI.

Disaggregation and estimation of genetic effects from offspring and parents has long been of interest to statistical geneticists. Recently, technical and methodological advances have made the genome-wide and loci-specific estimation of direct offspring and parental genetic nurture effects more possible. However, unbiased estimation using these methods requires datasets where both parents and at least one child have been genotyped, which are relatively scarce. Our group has recently developed a method and accompanying software (IMPISH; Hwang et al. in PLoS Genet 16:e1009154, 2020) which is able to impute missing parental genotypes from observed data on sibships and estimate their effects on an offspring phenotype conditional on the effects of genetic transmission. However, this method is unable to disentangle maternal and paternal effects, which may differ in magnitude and direction. Here, we introduce an extension to the original IMPISH routine which takes advantage of all available nuclear families to impute parent-specific missing genotypes and obtain asymptotically unbiased estimates of genetic effects on offspring phenotypes. We apply this this method to data from related individuals in the UK Biobank, showing concordance with previous estimates of maternal genetic effects on offspring birthweight. We also conduct the first GWAS jointly estimating offspring-, maternal-, and paternal-specific genetic effects on body-mass index.

Plant-arthropod interactions of an endangered California lupine.

The reintroduction of endangered plant species is an essential conservation tool. Reintroductions can fail to create resilient, self-sustaining populations due to a poor understanding of environmental factors that limit or promote plant success. Biotic factors, specifically plant-arthropod interactions, have been shown to affect the establishment of endangered plant populations. Lupinus nipomensis (Nipomo Mesa lupine) is a state of California (California Rare Plant Rank: 1B.1) and federally (65 FR 14888) endangered endemic plant with only one extant population located along the central California coast. How arthropods positively or negatively interact with L. nipomensis is not well known and more information could aid conservation efforts. We conducted arthropod surveys of the entire L. nipomensis extant population in spring 2017. Observed arthropods present on L. nipomensis included 17 families, with a majority of individuals belonging to Thripidae. We did not detect any obvious pollinators of L. nipomensis, providing support for previous studies suggesting this lupine is capable of self-pollinating, and observed several arthropod genera that could potentially impact the reproductive success of L. nipomensis via incidental pollination or plant predation.

Adjustments in physiological and morphological traits suggest drought-induced competitive release of some California plants.

Drought and competition affect how morphological and physiological traits are expressed in plants. California plants were previously found to respond less negatively to resource limitation compared to invasive counterparts. In a glasshouse in Santa Cruz, CA, USA, we exposed five native California C3 grassland species to episodic drought and competition (via five locally invasive species). We hypothesized that leaf morphology would be more affected by competition, and leaf photosynthetic gas exchange more so by drought, consistent with optimal partitioning and environmental filter theories. We expected that traits would exhibit trade-offs along a spectrum for resource conservatism versus acquisition. Bromus carinatus had greater photosynthetic recovery, while Diplacus aurantiacus had lower percent loss of net assimilation (PLA) and intrinsic water-use efficiency (iWUE) during drought and competition simultaneously compared to just drought. Stipa pulchra and Sidalcea malviflora gas exchange was unaffected by drought, and leaf morphology exhibited drought-related adjustments. Lupinus nanus exhibited trait adjustments for competition but not drought. Functional traits sorted onto two principal components related to trade-offs for resource conservatism versus acquisition, and for above- versus belowground allocation. In summary, morphological traits were affected by competition and drought, whereas physiological traits, like leaf gas exchange, were primarily affected by drought. The grassland plants we studied showed diverse responses to drought and competition with trait trade-offs related to resource conservatism versus acquisition, and for above- versus belowground allocation consistent with optimal partitioning and environmental filter theories. Diplacus aurantiacus experienced competitive release based on greater iWUE and lower PLA when facing drought and competition.

Overcoming biotic homogenization in ecological restoration.

Extensive evidence shows that regional (gamma) diversity is often lower across restored landscapes than in reference landscapes, in part due to common restoration practices that favor widespread species through selection of easily-grown species with high survival and propagation practices that reduce genetic diversity. We discuss approaches to counteract biotic homogenization, such as reintroducing species that are adapted to localized habitat conditions and are unlikely to colonize naturally; periodically reintroducing propagules from remnant populations to increase genetic diversity; and reintroducing higher trophic level fauna to restore interaction networks and processes that promote habitat heterogeneity. Several policy changes would also increase regional diversity; these include regional coordination amongst restoration groups, financial incentives to organizations producing conservation-valued species, and experimental designations for rare species introductions.