American journal of human genetics

A transcriptome-wide association study (TWAS) is a popular statistical method for identifying genes whose genetically regulated expression (GReX) component is associated with a trait of interest. Most TWAS approaches fundamentally assume th…

Female infertility is a common and complex health problem affecting millions of women worldwide. While multiple factors can contribute to this condition, the underlying cause remains elusive in up to 15%-30% of affected individuals. In our …

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases an…

Theory for liability-scale models of the underlying genetic basis of complex disease provides an important way to interpret, compare, and understand results generated from biological studies. In particular, through estimation of the liabili…

The low portability of polygenic scores (PGSs) across global populations is a major concern that must be addressed before PGSs can be used for everyone in the clinic. Indeed, prediction accuracy has been shown to decay as a function of the …

Population-scale biobanks that combine genetic data and high-dimensional phenotyping for a large number of participants provide an exciting opportunity to perform genome-wide association studies (GWAS) to identify genetic variants associate…

Quantifying the functional effects of complex disease risk variants can provide insights into mechanisms underlying disease biology. Genome-wide association studies have identified 39 regions associated with risk of epithelial ovarian cance…

Genome-wide association studies (GWASs) have reproducibly associated variants within intergenic regions of 1p36.12 locus with osteoporosis, but the functional roles underlying these noncoding variants are unknown. Through an integrative fun…

Whole-genome sequencing across multiple samples in a population provides an unprecedented opportunity for comprehensively characterizing the polymorphic variants in the population. Although the 1000 Genomes Project (1KGP) has offered brief …

Uterine leiomyomata (UL), the most prevalent pelvic tumors in women of reproductive age, pose a major public health problem given their high frequency, associated morbidities, and most common indication for hysterectomies. A genetic compone…

Predictive genomic profiling used to produce personalized nutrition and other lifestyle health recommendations is currently offered directly to consumers. By examining previous meta-analyses and HuGE reviews, we assessed the scientific evid…

Endometriosis is a common gynecological disease that affects up to 10% of women in their reproductive years. It causes pelvic pain, severe dysmenorrhea, and subfertility. The disease is defined as the presence of tissue resembling endometri…

The important role of genetics in pediatric illness has been increasingly recognized, but the true impact has not been well delineated. An important study of pediatric inpatient admissions to a children's hospital in 1978 found a genetic ba…

We measured the proportion of mutant mtDNA (mutation load) in 82 primary oocytes from a woman who harbored the A3243G mtDNA mutation. The frequency distribution of mutation load indicates that random drift is the principal mechanism that de…

Mutations in the FBN1 gene cause Marfan syndrome (MFS), a dominantly inherited connective tissue disease. Almost all the identified FBN1mutations have been family specific, and the rate of new mutations is high. We report here a de novo FBN…

The construction of an accurate family pedigree is a fundamental component of a clinical genetic evaluation and of human genetic research. Previous surveys of genetic counselors and human genetic publications have demonstrated significant i…