A polygenic risk score for Alzheimer's disease constructed using APOE-region variants has stronger association than APOE alleles with mild cognitive impairment in Hispanic/Latino adults in the U.S.

Introduction: Polygenic Risk Scores (PRSs) are summaries of genetic risk alleles for an outcome.

Methods: We used summary statistics from five GWASs of AD to construct PRSs in 4,189 diverse Hispanics/Latinos (mean age 63 years) from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA). We assessed the PRS associations with MCI in the combined set of people and in diverse subgroups, and when including and excluding the APOE gene region.

Genetic loci of beta-aminoisobutyric acid are associated with aging-related mild cognitive impairment.

We studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)-the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed their association with MCI in datasets of diverse race/ethnicities. We first performed a GWAS for the MCI-MRS and BAIBA, in Hispanic/Latino adults (n = 3890) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We identified ten independent genome-wide significant (p value <5 × 10) variants associated with MCI-MRS or BAIBA.

Interaction analysis of ancestry-enriched variants with APOE-ɛ4 on MCI in the Study of Latinos-Investigation of Neurocognitive Aging.

APOE-ɛ4 risk on Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD) differs between race/ethnic groups, presumably due to ancestral genomic background surrounding the APOE locus. We studied whether African and Amerindian ancestry-enriched genetic variants in the APOE region modify the effect of the APOE-ɛ4 alleles on Mild Cognitive Impairment (MCI) in Hispanics/Latinos. We defined African and Amerindian ancestry-enriched variants as those common in one Hispanic/Latino parental ancestry and rare in the other two.

Genetic associations between sleep traits and cognitive ageing outcomes in the Hispanic Community Health Study/Study of Latinos.

Background: Sleep phenotypes have been reported to be associated with cognitive ageing outcomes. However, there is limited research using genetic variants as proxies for sleep traits to study their associations. We estimated associations between Polygenic Risk Scores (PRSs) for sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnoea (OSA) and measures of cogntive ageing in Hispanic/Latino adults.

Awareness and utilization of genetic testing among Hispanic and Latino adults living in the US: The Hispanic Community Health Study/Study of Latinos.

We investigated the awareness, perceived usefulness, and use of genetic testing among Hispanic and Latino individuals. Annual follow-up surveys for the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) from 2019 to April 2020 assessed participants' level of awareness and use of genetic tests to determine disease risks, likelihood of passing disease to children, disease treatment, or drug selection. They also were asked to rate the usefulness of the tests for managing a person's health on a 1 (not at all useful) to 10 (extremely useful) scale.

Plasma metabolites associated with cognitive function across race/ethnicities affirming the importance of healthy nutrition.

Introduction: We studied the replication and generalization of previously identified metabolites potentially associated with global cognitive function in multiple race/ethnicities and assessed the contribution of diet to these associations.

Methods: We tested metabolite-cognitive function associations in U.S.

AFA: Ancestry-specific allele frequency estimation in admixed populations: The Hispanic Community Health Study/Study of Latinos.

Allele frequency estimates in admixed populations, such as Hispanics and Latinos, rely on the sample's specific admixture composition and thus may differ between two seemingly similar populations. However, ancestry-specific allele frequencies, i.e.

Blood metabolites predicting mild cognitive impairment in the study of Latinos-investigation of neurocognitive aging (HCHS/SOL).

Introduction: Blood metabolomics-based biomarkers may be useful to predict measures of neurocognitive aging.

Methods: We tested the association between 707 blood metabolites measured in 1451 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), with mild cognitive impairment (MCI) and global cognitive change assessed 7 years later. We further used Lasso penalized regression to construct a metabolomics risk score (MRS) that predicts MCI, potentially identifying a different set of metabolites than those discovered in individual-metabolite analysis.

Utility of polygenic embryo screening for disease depends on the selection strategy.

Polygenic risk scores (PRSs) have been offered since 2019 to screen in vitro fertilization embryos for genetic liability to adult diseases, despite a lack of comprehensive modeling of expected outcomes. Here we predict, based on the liability threshold model, the expected reduction in complex disease risk following for a single disease. A strong determinant of the potential utility of such screening is the , a factor that has not been previously studied.

APOE alleles' association with cognitive function differs across Hispanic/Latino groups and genetic ancestry in the study of Latinos-investigation of neurocognitive aging (HCHS/SOL).

Introduction: Apolipoprotein E (APOE) alleles are associated with cognitive decline, mild cognitive impairment (MCI), and Alzheimer's disease in Whites, but have weaker and inconsistent effects reported in Latinos. We hypothesized that this heterogeneity is due to ancestry-specific genetic effects.

Methods: We investigated the associations of the APOE alleles with significant cognitive decline and MCI in 4183 Latinos, stratified by six Latino backgrounds, and explored whether the proportion of continental genetic ancestry (European, African, and Amerindian) modifies these associations.

Searching for parent-of-origin effects on cardiometabolic traits in imprinted genomic regions.

Cardiometabolic traits pose a major global public health burden. Large-scale genome-wide association studies (GWAS) have identified multiple loci accounting for up to 30% of the genetic variance in complex traits such as cardiometabolic traits. However, the contribution of parent-of-origin effects (POEs) to complex traits has been largely ignored in GWAS.

Associations of autozygosity with a broad range of human phenotypes.

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (F) for >1.

A study of Kibbutzim in Israel reveals risk factors for cardiometabolic traits and subtle population structure.

Genetic studies in isolated populations often increase power for identifying loci associated with complex diseases and traits. We present here the Kibbutzim Family Study (KFS), aimed at investigating the genetic basis of cardiometabolic traits in extended Israeli families characterized by long-term social stability and a homogeneous environment. Extensive information on cardiometabolic traits, as well as genome-wide genotypes, were collected on 901 individuals.

Parent-of-Origin Effects of the APOB Gene on Adiposity in Young Adults.

Loci identified in genome-wide association studies (GWAS) of cardio-metabolic traits account for a small proportion of the traits' heritability. To date, most association studies have not considered parent-of-origin effects (POEs). Here we report investigation of POEs on adiposity and glycemic traits in young adults.

Associations of maternal pre-pregnancy and gestational body size with offspring longitudinal change in BMI.

Objectives: Studies demonstrate associations between changes in obesity-related phenotypes and cardiovascular risk. Although maternal pre-pregnancy BMI (mppBMI) and gestational weight gain (GWG) may be associated with adult offspring adiposity, no study has examined associations with obesity changes. Associations of mppBMI and GWG with longitudinal change in offspring's BMI (ΔBMI) were examined, and whether associations are explained by offspring genetics was assessed.

Complex chromosomal rearrangement in a girl with psychomotor-retardation and a de novo inversion: inv(2)(p15;q24.2).

Cytogenetic analysis of DNA from a girl with severe psychomotor retardation revealed a de novo pericentric inversion of chromosome 2: 46,XX,inv(2)(p15q24.2). In order to elucidate the possible role of the inversion in the girl's abnormal phenotype, we analyzed the inversion breakpoints.

Identification of a functional rare variant in autism using genome-wide screen for monoallelic expression.

Recent work has led to the identification of several susceptibility genes for autism spectrum disorder (ASD) and an increased appreciation of the importance of rare and de novo mutations. Some of the mutations may be very hard to detect using current strategies, especially if they are located in regulatory regions. We present a new approach to identify functional mutations that exploit the fact that many rare mutations disrupt the expression of genes from a single parental chromosome.