bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2020.03.04.977389

Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS

Peyrot, W. J.·Price, A. L.
View original source ↗Export metadata ↓

Abstract

Psychiatric disorders are highly genetically correlated, and many studies have focused on their shared genetic components. However, little research has been conducted on the genetic differences between psychiatric disorders, because case-case comparisons of allele frequencies among cases currently require individual-level data from cases of both disorders. We developed a new method (CC-GWAS) to test for differences in allele frequency among cases of two different disorders using summary statistics from the respective case-control GWAS; CC-GWAS relies on analytical assessments of the genetic distance between cases and controls of each disorder. Simulations and analytical computations confirm that CC-GWAS is well-powered and attains effective control of type I error. In particular, CC-GWAS identifies and discards false positive associations that can arise due to differential tagging of a shared causal SNP (with the same allele frequency in cases of both disorders), e.g. due to subtle differences in ancestry between the input case-control studies. We applied CC-GWAS to publicly available summary statistics for schizophrenia, bipolar disorder and major depressive disorder, and identified 116 independent genome-wide significant loci distinguishing these three disorders, including 21 CC-GWAS-specific loci that were not genome-wide significant in the input case-control summary statistics. Two of the CC-GWAS-specific loci implicate the genes KLF6 and KLF16 from the Kruppel-like family of transcription factors; these genes have been linked to neurite outgrowth and axon regeneration. We performed a broader set of case-case comparisons by additionally analyzing ADHD, anorexia nervosa, autism, obsessive-compulsive disorder and Tourettes Syndrome, yielding a total of 196 independent loci distinguishing eight psychiatric disorders, including 72 CC-GWAS-specific loci. We confirmed that loci identified by CC-GWAS replicated convincingly in applications to data sets for which independent replication data were available. In conclusion, CC-GWAS robustly identifies loci with different allele frequencies among cases of different disorders using results from the respective case-control GWAS, providing new insights into the genetic differences between eight psychiatric disorders.

Source connections

Explore related subjects

geneticsPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Peyrot, W. J., Price, A. L.. 2020-03-05. Identifying loci with different allele frequencies among cases of eight psychiatric disorders using CC-GWAS. https://doi.org/10.1101/2020.03.04.977389

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

The histone demethylase Kdm5 and the ARGONAUTE proteins Piwi and Aubergine regulate female abdominal pigmentation in Drosophila melanogaster

Insect pigmentation is an ecologically critical trait influencing many physiological processes. In Drosophila melanogaster, abdominal pigmentation is sexually dimorphic: males have fully pigmented posterior segments, while females exhibit a posterior melanin stripe. Pigmentation relies on the expression of pigmentation genes that encode enzymes involved in pigment synthesis. These genes are tightly regulated during pupal and young adult stages. To expand the gene regulatory network of pigmentation genes, we conducted an RNAi screen using the yellow-Gal4 driver, expressed during the pupal stage in abdominal epidermis. One of the candidates from this screen, Kdm5, encodes a histone demethylase erasing the H3K4me3 histone mark catalyzed by the histone methyl-transferase Trithorax (Trx). We show that Kdm5 down-regulation reduces abdominal pigmentation, mimicking trx down-regulation. Kdm5 activates melanin production through regulation of the pigmentation gene tan. Transcriptomic analyses reveal that Kdm5 and Trx share many targets in pupal abdominal epidermis, including piRNA pathway components such as piwi and aubergine. These piRNA components, originally associated with transposon silencing in the germline, also function in some somatic tissues such as the nervous system, the fat body or the gut. We demonstrate that Piwi and Aubergine participate in female abdominal pigmentation establishment, without evident piRNA production. We also show that Kdm5 and Piwi act not only in pupal abdominal epidermis but also in pupal fat body. This study therefore expands the regulatory network of pigmentation genes. It identifies a new somatic function for Kdm5 and Piwi and reveals a role for pupal fat body in female abdominal pigmentation regulation.

genetics↗
bioRxiv2026

Genetic diversity within and between polyploid sugarcane (Saccharum spp.) families obtained via caryopsis using microsatellite markers and multicategory model

Genetic diversity analyses are essential for sugarcane (Saccharum spp.) breeding programs. Crossbreeding, based on genetic distances between parental plants, is a tool used to increase genetic variability and enhance plant selection; however, quantifying variation in highly polyploid species remains a challenge. The present study aimed to evaluate the diversity within and between 12 families of sugarcane derived from caryopses, analyzing 120 individual seedlings arranged in an augmented block design. Genotyping was performed using primers for 16 microsatellite loci, five simple sequence repeat (SSR) loci, and 11 expressed sequence tag-SSR (EST-SSR) loci. To accurately account for polyploidy, similarity calculations were performed using Bruvos distances among individuals and RST distances among the families. Analysis of molecular variance (AMOVA) indicated that most of the genetic variability was within families (72%), with only 28% found between them. This high level of intra-family variation demonstrates that a significant reservoir of genetic diversity remains available within the crosses. The highest genetic similarity was observed between the families RB986952 x RB986960 and RB036122 x RB03611, whereas the lowest genetic similarity was observed between the families RB97319 x RB966928 and RB106802 x RB855036. Although the evaluated families shared high genetic similarity, the pronounced genetic variation within them demonstrates a robust recombination potential, indicating that the genetic basis of sugarcane can be better explored using the high variability that already exists in the selection of desirable morpho-agronomic characteristics within the families. Furthermore, this study highlights the importance of using appropriate distances for diversity studies with codominant markers, such as microsatellites, in polyploid species.

genetics↗
bioRxiv2026

Optimizing DNA extraction from environmentally degraded bone samples for molecular identification of cetacean species

Molecular identification of cetacean bone remains can be limited by DNA degradation and the presence of PCR inhibitors. Here, we present an optimized DNA extraction protocol based on a total demineralization method for environmentally exposed cetacean bones. The protocol uses 100 mg of bone powder, 24 h digestion with EDTA, N-lauroylsarcosine, and proteinase K, followed by a modified silica-column purification. Nine environmentally degraded bone samples representing eight individuals were processed. DNA concentrations ranged from 7.3 to 57.1 ng/uL (mean SD = 25.91- 13.91 ng/uL). The mitochondrial cytochrome b gene was successfully amplified from all samples using conventional PCR, and five samples (55.6%) yielded sequences suitable for downstream analysis. BLASTn identified Balaenoptera physalus as the closest database match for all recovered sequences, and phylogenetic analysis further supported their association with B. physalus reference sequences. These results demonstrate that the proposed protocol provides a practical approach for recovering amplifiable and molecularly informative mitochondrial DNA from environmentally degraded cetacean bone material, facilitating molecular identification from challenging skeletal remains.

genetics↗