Publications by authors named "Qin-Qin Huang"

Although rare neurodevelopmental conditions have a large Mendelian component, common genetic variants also contribute to risk. However, little is known about how this polygenic risk is distributed among patients with these conditions and their parents nor its interplay with rare variants. It is also unclear whether polygenic background affects risk directly through alleles transmitted from parents to children, or whether indirect genetic effects mediated through the family environment also play a role.

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  • Human genetic studies reveal new insights into the biological processes of ovarian aging through rare protein-coding variants in a large study of women.
  • The genes identified (e.g., SAMHD1 and ZNF518A) show stronger effects on reproductive lifespan and cancer risk compared to common variants, with some variants linked to earlier menopause.
  • The research suggests a connection between genetic factors influencing ovarian aging and an increased incidence of de novo mutations, highlighting the importance of DNA damage response in fertility.
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Polygenic risk scores (PRSs) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. We propose PRSmix, a framework that leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture for 47 and 32 diseases/traits in European and South Asian ancestries, respectively. PRSmix demonstrated a mean prediction accuracy improvement of 1.

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  • - A new multi-ancestry genome-wide association study (GWAS) of major depression (MD) analyzed data from 88,316 cases and 902,757 controls, representing various ancestries including African, East Asian, South Asian, and Hispanic/Latin American.
  • - The study discovered 53 novel genetic loci significantly linked to MD, with fewer existing European ancestry loci proving relevant to other ancestry groups.
  • - A transcriptome-wide association study in this research identified 205 new genes associated with MD, highlighting the importance of diverse ancestry in genetic research for better understanding and finding relevant genes.
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Autozygosity is associated with rare Mendelian disorders and clinically relevant quantitative traits. We investigated associations between the fraction of the genome in runs of homozygosity (F) and common diseases in Genes & Health (n = 23,978 British South Asians), UK Biobank (n = 397,184), and 23andMe. We show that restricting analysis to offspring of first cousins is an effective way of reducing confounding due to social/environmental correlates of F.

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  • The study examined the genetic basis of various structural features of the human cerebral cortex using data from over 36,000 individuals and identified 4,349 significant genetic locations linked to cortical traits.
  • Researchers explored 13 different phenotypes, including thickness, surface area, and water diffusion, and found four genetic structures that suggest different developmental gene expression paths.
  • The findings highlight complex relationships among the identified phenotypes and suggest that genetic variants related to cortical expansion may also be linked to certain head disorders, emphasizing the genetic organization of the cortex and its developmental implications.
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  • The melanocortin 3 receptor (MC3R) is important for regulating puberty, growth, and lean mass, and its variants may affect pubertal timing in humans.
  • The study aimed to find how often harmful MC3R variants occur in patients with constitutional delay of growth and puberty (CDGP) compared to those with normosmic idiopathic hypogonadotropic hypogonadism (nIHH).
  • Results showed that MC3R loss-of-function variants were more common in CDGP patients, but not in those with nIHH, and such variants were also linked to delayed menarche in a broader UK Biobank cohort.
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Polygenic risk scores (PRS) are an emerging tool to predict the clinical phenotypes and outcomes of individuals. Validation and transferability of existing PRS across independent datasets and diverse ancestries are limited, which hinders the practical utility and exacerbates health disparities. We propose PRSmix, a framework that evaluates and leverages the PRS corpus of a target trait to improve prediction accuracy, and PRSmix+, which incorporates genetically correlated traits to better capture the human genetic architecture.

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Individuals with South Asian ancestry have a higher risk of heart disease than other groups but have been largely excluded from genetic research. Using data from 22,000 British Pakistani and Bangladeshi individuals with linked electronic health records from the Genes & Health cohort, we conducted genome-wide association studies of coronary artery disease and its key risk factors. Using power-adjusted transferability ratios, we found evidence for transferability for the majority of cardiometabolic loci powered to replicate.

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Background: Type 2 diabetes (T2D) is highly prevalent in British South Asians, yet they are underrepresented in research. Genes & Health (G&H) is a large, population study of British Pakistanis and Bangladeshis (BPB) comprising genomic and routine health data. We assessed the extent to which genetic risk for T2D is shared between BPB and European populations (EUR).

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Previous genetic and public health research in the Pakistani population has focused on the role of consanguinity in increasing recessive disease risk, but little is known about its recent population history or the effects of endogamy. Here, we investigate fine-scale population structure, history and consanguinity patterns using genotype chip data from 2,200 British Pakistanis. We reveal strong recent population structure driven by the biraderi social stratification system.

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Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro.

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Chronic immune-mediated diseases of adulthood often originate in early childhood. To investigate genetic associations between neonatal immunity and disease, we map expression quantitative trait loci (eQTLs) in resting myeloid cells and CD4 T cells from cord blood samples, as well as in response to lipopolysaccharide (LPS) or phytohemagglutinin (PHA) stimulation, respectively. Cis-eQTLs are largely specific to cell type or stimulation, and 31% and 52% of genes with cis-eQTLs have response eQTLs (reQTLs) in myeloid cells and T cells, respectively.

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By sequencing autozygous human populations, we identified a healthy adult woman with lifelong complete knockout of (expected ~1 in 30 million outbred people). (glycolate oxidase) silencing is the mechanism of lumasiran, an investigational RNA interference therapeutic for primary hyperoxaluria type 1. Her plasma glycolate levels were 12 times, and urinary glycolate 6 times, the upper limit of normal observed in healthy reference individuals (n = 67).

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Cytokines are essential regulatory components of the immune system, and their aberrant levels have been linked to many disease states. Despite increasing evidence that cytokines operate in concert, many of the physiological interactions between cytokines, and the shared genetic architecture that underlies them, remain unknown. Here, we aimed to identify and characterize genetic variants with pleiotropic effects on cytokines.

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Investigation of the genetic architecture of gene expression traits has aided interpretation of disease and trait-associated genetic variants; however, key aspects of expression quantitative trait loci (eQTL) study design and analysis remain understudied. We used extensive, empirically driven simulations to explore eQTL study design and the performance of various analysis strategies. Across multiple testing correction methods, false discoveries of genes with eQTLs (eGenes) were substantially inflated when false discovery rate (FDR) control was applied to all tests and only appropriately controlled using hierarchical procedures.

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  • Traditional genome-wide scans have mainly revealed selective sweeps for simple traits, overlooking the more common polygenic traits like coronary artery disease (CAD).
  • This research identified new genetic loci influenced by positive selection related to CAD and reproductive traits, indicating that selection pressures may be linked to both health and reproductive success.
  • The findings suggest that there are trade-offs in the evolution of CAD and reproductive success, showing that modern human genomes have adapted due to CAD-induced selection and early-life traits that are interconnected.
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In the title compound, C(13)H(12)N(2)O(4), the dihedral angle between the benzene and pyrimidine rings is 55.57 (13)°. The carbonyl group and the two methoxyl groups are approximately coplanar with the benzene ring and pyrimidine ring; the C-C-C-O, C-O-C-N and C-O-C-C torsion angles being -6.

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