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Open Access Publications from the University of California

Scholarly Works (85 results)

  • Article
  • Peer Reviewed
UC San Francisco Previously Published Works (2009)
A report on the Genomic Disorders conference on Genomic Variation in Health and Disease, Hinxton, UK, 9-11 March, 2009.
    Cover page: New insights into genomic variation in health and disease
    • Thesis
    • Peer Reviewed
    UC Berkeley Electronic Theses and Dissertations (2016)

    We live in a golden era of exoplanet discovery and characterization. Since its launch in 2009, the Kepler Mission has discovered over 4000 exoplanets, enabling detailed studies of their physical and orbital properties. These include empirical studies of the prevalence of planets of various sizes and orbital distances. In some of the Kepler systems, the compositions of the planets have been determined. Other studies include empirical, analytical, and numerical constraints on the formation and evolution of planetary systems.

    This thesis focuses on two aspects of the Kepler revolution. The first focus is on the masses and densities of small planets. Planets smaller than Neptune span a variety of compositions. Some of them are rocky and potentially habitable. The diversity of compositions among sub-Neptunes offers clues to planet formation and evolution. To determine the compositions of small planets, it is necessary to compute bulk densities from measurements of the planet radii and masses. While Kepler has determined the radii of thousands of planets, only a handful of the small planets are amenable to mass measurement techniques. Using the results from two mass measurement techniques, called the radial velocity (or Doppler) method and the transit timing variation method, a detailed study of the masses and compositions of more than 65 small planets was conducted. This study determined empirical relationships that describe the average masses and densities of exoplanets smaller than Neptune as a function of planet radius. Such exoplanets achieve a peak bulk density of 7.6 grams per cubic centimeter at a physical size of 1.5 times the radius of Earth. This peak density corresponds to a rocky composition; rocky planets smaller than 1.5 Earth radii are less compressed and less dense, whereas planets larger than 1.5 Earth radii have thick envelopes composed of volatile gases that lower their bulk densities.

    The second focus of this thesis is on the masses and orbital dynamics of planets in multi- planet systems. Multi-planet systems represent the end-states of planet formation. Their orbital dynamics and planet compositions are a fossil record of how they arrived at their present configurations. The systems studied herein include 3 multi-planet systems: KOI- 94, Kepler-10, and Kepler-11. KOI-94 is a system of 4 planets including a warm Jovian world. Kepler-10 contains a scorched rocky planet, a cooler gas-enveloped world, and a likely third planet. Kepler-11 has six small planets with fluffy hydrogen-rich envelopes, all contained within the equivalent orbital distance of Venus. Measurements of the compositions and orbital dynamics of these planets offer valuable steps toward characterizing the possible formation and evolutionary histories of these planetary systems.

      Cover page: The Masses and Orbital Dynamics of Exoplanets
      • Article
      • Peer Reviewed
      UC San Francisco Previously Published Works (2022)
      Phenotypic differences across sexes are pervasive, but the genetic architecture of sex differences within and across phenotypes is mostly unknown. In this study, we aimed to improve detection power for sex-differentially contributing SNPs previously demonstrated to be enriched in disease association, and we investigate their functions in health, pathophysiology, and genetic function. We leveraged GIANT and UK Biobank summary statistics and defined a set of 2,320 independent SNPs having sexually dimorphic effects within and across biometric traits (MAF > 0.001, P < 5x10-8). Biometric trait sex-heterogeneous SNPs (sex-het SNPs) showed enrichment in association signals for 20 out of 33 diseases/traits at 5% alpha compared to sex-homogeneous matched SNPs (empP < 0.001), and were significantly overrepresented in muscle, skeletal and stem cell development processes, and in calcium channel and microtubule complexes (FDR < 0.05, empP < 0.05). Interestingly, we found that sex-het SNPs significantly map to predicted expression quantitative trait loci (Pr-eQTLs) across brain and other tissues, methylation quantitative trait loci (meQTLs) during development, and transcription start sites, compared to sex-homogeneous SNPs. Finally, we verified that the sex-het disease/trait enrichment was not explained by Pr-eQTL enrichment alone, as sex-het Pr-eQTLs were more enriched than matched sex-homogeneous Pr-eQTLs. We conclude that genetic polymorphisms with sexually dimorphic effects on biometric traits not only contribute to fundamental embryogenic processes, but later in life play an outsized role in disease risk. These sex-het SNPs disproportionately influence gene expression and have a greater influence on disorders of body and brain than other expression-regulatory variation. Together, our data emphasize the genetic underpinnings of sexual dimorphism and its role in human health.
        Cover page: Sex-heterogeneous SNPs disproportionately influence gene expression and health
        • Article
        • Peer Reviewed
        UC San Francisco Previously Published Works (2013)
        To date, genome-wide single nucleotide polymorphism (SNP) and copy number variant (CNV) association studies of autism spectrum disorders (ASDs) have led to promising signals but not to easily interpretable or translatable results. Our own genome-wide association study (GWAS) showed significant association to an intergenic SNP near Semaphorin 5A (SEMA5A) and provided evidence for reduced expression of the same gene. In a novel GWAS follow-up approach, we map an expression regulatory pathway for a GWAS candidate gene, SEMA5A, in silico by using population expression and genotype data sets. We find that the SEMA5A regulatory network significantly overlaps rare autism-specific CNVs. The SEMA5A regulatory network includes previous autism candidate genes and regions, including MACROD2, A2BP1, MCPH1, MAST4, CDH8, CADM1, FOXP1, AUTS2, MBD5, 7q21, 20p, USH2A, KIRREL3, DBF4B and RELN, among others. Our results provide: (i) a novel data-derived network implicated in autism, (ii) evidence that the same pathway seeded by an initial SNP association shows association with rare genetic variation in ASDs, (iii) a potential mechanism of action and interpretation for the previous autism candidate genes and genetic variants that fall in this network, and (iv) a novel approach that can be applied to other candidate genes for complex genetic disorders. We take a step towards better understanding of the significance of SEMA5A pathways in autism that can guide interpretation of many other genetic results in ASDs.
          Cover page: An eQTL mapping approach reveals that rare variants in the SEMA5A regulatory network impact autism risk
          • Article
          • Peer Reviewed
          UC San Francisco Previously Published Works (2016)
            • Article
            • Peer Reviewed
            UC San Francisco Previously Published Works (2018)
            Personality is a complex, yet partially heritable, trait. Although some Mendelian diseases like Williams-Beuren syndrome are associated with a particular personality profile, studies have failed to assign the personality features to a single gene or pathway. As a family of monogenic disorders caused by mutations in the Ras/MAPK pathway known to influence social behavior, RASopathies are likely to provide insight into the genetic basis of personality. Eighty subjects diagnosed with cardiofaciocutaneous syndrome, Costello syndrome, neurofibromatosis type 1, and Noonan syndrome were assessed using a parent-report BFQ-C (Big Five Questionnaire for Children) evaluating agreeableness, extraversion, conscientiousness, intellect/openness, and neuroticism, along with 55 unaffected sibling controls. A short questionnaire was added to assess sense of humor. RASopathy subjects and sibling controls were compared for individual components of personality, multidimensional personality profiles, and individual questions using Student tests, analysis of variance, and principal component analysis. RASopathy subjects were given lower scores on average compared to sibling controls in agreeableness, extraversion, conscientiousness, openness, and sense of humor, and similar scores in neuroticism. When comparing the multidimensional personality profile between groups, RASopathies showed a distinct profile from unaffected siblings, but no difference in this global profile was found within RASopathies, revealing a common profile for the Ras/MAPK-related disorders. In addition, several syndrome-specific strengths or weaknesses were observed in individual domains. We describe for the first time an association between a single pathway and a specific personality profile, providing a better understanding of the genetics underlying personality, and new tools for tailoring educational and behavioral approaches for individuals with RASopathies.
              Cover page: RASopathies are associated with a distinct personality profile
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2018)

              Objective

              To identify frequently reported prescription medications and supplements among couples planning pregnancy because there is a lack of descriptive information on these agents in women and men who are trying to conceive.

              Methods

              Five hundred one couples enrolled in the Longitudinal Study of Infertility and the Environment, which took place between 2005 and 2009. Participants reported prescription medications as well as prescription and over-the-counter supplements used through interviews at study enrollment and through daily dairies during the 12-month follow-up. We identified prescription medications and supplements prospectively reported by ≥1% of women and men at baseline and from daily journal information grouped into 3-month preconception follow-up intervals while couples tried for pregnancy.

              Results

              The 5 most reported prescription medications among women were levothyroxine (5.8%), cetirizine (2.6%), fluticasone (2.4%), escitalopram (1.8%), and fluoxetine (1.8%) and for men were lisinopril (2.0%), mometasone (2.0%), fexofenadine (1.8%), atorvastatin (1.6%), and montelukast (1.6%). The most reported supplements were multivitamins (63.3%, 43.5%) and fish oil (13.2%, 9.4%) for women and men, respectively, and prenatal vitamins (22.0%) for women. For women during the first 3 months of follow-up, prenatal vitamins (6.0%) and antibiotics (1.2%-2.6%) were among the most frequently started medications. During the next 3 months, clomiphene (4.5%) was the most frequently initiated medication.

              Conclusions

              Couples trying for pregnancy reported a variety of prescription medications and supplements, and they differed by gender. Preconception guidance should address medication and supplement use to avoid potential exposures associated with adverse reproductive and perinatal outcomes.
                Cover page: Most Frequently Reported Prescription Medications and Supplements in Couples Planning Pregnancy: The LIFE Study
                • Article
                • Peer Reviewed
                UC San Francisco Previously Published Works (2017)

                Background

                Prior studies suggest neurodevelopmental impacts of polybrominated diphenyl ethers (PBDEs), but few have examined diagnosed developmental disorders.

                Objectives

                Our aim was to determine whether prenatal exposure to brominated flame retardants (BFRs) is associated with autism spectrum disorder (ASD) or intellectual disability without autism (ID).

                Methods

                We conducted a population-based case-control study including children with ASD (n=545) and ID (n=181) identified from the California Department of Developmental Services and general population (GP) controls (n=418) from state birth certificates. ASD cases were matched to controls by sex, birth month, and birth year. Concentrations of 10 BFRs were measured in maternal second trimester serum samples stored from routine screening. Logistic regression was used to calculate crude and adjusted odds ratios (AOR) for associations with ASD, and separately for ID, compared with GP controls, by quartiles of analyte concentrations in primary analyses.

                Results

                Geometric mean concentrations of five of the six congeners with ≥55% of samples above the limit of detection were lower in mothers of children with ASD or ID than in controls. In adjusted analyses, inverse associations with several congeners were found for ASD relative to GP (e.g., quartile 4 vs. 1, BDE-153: AOR=0.56, 95% CI: 0.38, 0.84). When stratified by child sex (including 99 females with ASD, 77 with ID, and 73 with GP), estimates were consistent with overall analyses in boys, but in the opposite direction among girls, particularly for BDE-28 and -47 (AOR=2.58, 95% CI: 0.86, 7.79 and AOR=2.64, 95% CI: 0.97, 7.19, respectively). Similar patterns overall and by sex were observed for ID.

                Conclusions

                Contrary to expectation, higher PBDE concentrations were associated with decreased odds of ASD and ID, though not in girls. These findings require confirmation but suggest potential sexual dimorphism in associations with prenatal exposure to BFRs. https://doi.org/10.1289/EHP1079.
                  Cover page: Prenatal Serum Concentrations of Brominated Flame Retardants and Autism Spectrum Disorder and Intellectual Disability in the Early Markers of Autism Study: A Population-Based Case–Control Study in California
                  • Article
                  • Peer Reviewed
                  UC Berkeley Previously Published Works (2019)
                  Characterizing the dependence of the orbital architectures and formation environments on the eccentricity distribution of planets is vital for understanding planet formation. In this work, we perform statistical eccentricity studies of transiting exoplanets using transit durations measured via Kepler combined with precise and accurate stellar radii from the California-Kepler Survey and Gaia. Compared to previous works that characterized the eccentricity distribution from transit durations, our analysis benefits from both high-precision stellar radii (∼3%) and a large sample of ∼1000 planets. We observe that systems with only a single observed transiting planet have a higher mean eccentricity () than systems with multiple transiting planets (), in agreement with previous studies. We confirm the preference for high- and low-eccentricity subpopulations among the single transiting systems. Finally, we show suggestive new evidence that high-e planets in the Kepler sample are preferentially found around high-metallicity ([Fe/H] > 0) stars. We conclude by discussing the implications on planetary formation theories.
                    Cover page: The California-Kepler Survey. VIII. Eccentricities of Kepler Planets and Tentative Evidence of a High-metallicity Preference for Small Eccentric PlanetsCreative Commons 'BY' version 4.0 license
                    • Article
                    • Peer Reviewed
                    UC Berkeley Previously Published Works (2014)
                    Small planets, 1-4× the size of Earth, are extremely common around Sun-like stars, and surprisingly so, as they are missing in our solar system. Recent detections have yielded enough information about this class of exoplanets to begin characterizing their occurrence rates, orbits, masses, densities, and internal structures. The Kepler mission finds the smallest planets to be most common, as 26% of Sun-like stars have small, 1-2 R⊕ planets with orbital periods under 100 d, and 11% have 1-2 R⊕ planets that receive 1-4× the incident stellar flux that warms our Earth. These Earth-size planets are sprinkled uniformly with orbital distance (logarithmically) out to 0.4 the Earth-Sun distance, and probably beyond. Mass measurements for 33 transiting planets of 1-4 R⊕ show that the smallest of them, R < 1.5 R⊕, have the density expected for rocky planets. Their densities increase with increasing radius, likely caused by gravitational compression. Including solar system planets yields a relation: ρ = 2:32 + 3:19 R=R ⊕ [g cm(-3)]. Larger planets, in the radius range 1.5-4.0 R⊕, have densities that decline with increasing radius, revealing increasing amounts of low-density material (H and He or ices) in an envelope surrounding a rocky core, befitting the appellation ''mini-Neptunes.'' The gas giant planets occur preferentially around stars that are rich in heavy elements, while rocky planets occur around stars having a range of heavy element abundances. Defining habitable zones remains difficult, without benefit of either detections of life elsewhere or an understanding of life's biochemical origins.
                      Cover page: Occurrence and core-envelope structure of 1–4× Earth-size planets around Sun-like stars
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