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PubMed1988

Genetic and epidemiological studies on electrolyte transport systems in hypertension.

In recent years several different tests of cations in human cells have been studied to detect and to define possible roles in the development of essential hypertension. The goal of this report is to summarize what has been learned in genetic and epidemiological studies of human populations. The seven tests reviewed in greatest detail include sodium-lithium countertransport, intraerythrocytic sodium, sodium (or lithium)-potassium cotransport, lithium leak, sodium-potassium ATPase pump, sodium pump sites (ouabain binding), and circulating sodium pump inhibitor ('digoxin-like factor' in some studies). Countertransport, intraerythrocytic sodium and cotransport consistently show different values in hypertensives compared to normotensives and even in normotensives with a positive family history of hypertension when compared to controls without a positive family history. Thorough genetic studies have been carried out only for sodium-lithium countertransport and intraerythrocytic sodium. Both of these tests are highly heritable with a combination of both polygenic and major gene effects. Cotransport, leak, and pump sites also seem to be quite significantly heritable whereas the ATPase pump activity and the circulating pump inhibitor seem to be largely determined by nongenetic factors. Some of the most dramatic changes in these tests have been observed during pregnancy. Significant increases are seen in countertransport, cotransport, ouabain binding sites, and digoxin-like factor. Oral contraceptives also seem to affect at least cotransport. Plasma triglyceride level and body weight are some of the strongest correlates of countertransport, cotransport, and lithium leak. Cotransport increases with higher dietary sodium intake and decreases with the use of the diuretic medication. In the current developmental stage these tests have several significant limitations. In most population studies there is a considerable overlap of test values between persons with high and normal blood pressure. There are substantial variations in the methods used by different laboratories for the same tests. They are expensive, complex and usually must be done on fresh cells. There are conflicts between the results of several different reported studies that could be due to the way in which their subjects were selected, the effects of medications or other uncontrolled variables, or even due to the differences in laboratory methodologies.(ABSTRACT TRUNCATED AT 400 WORDS)

Biological Transport↗

PubMed2001

A genome-wide scan for coronary heart disease suggests in Indo-Mauritians a susceptibility locus on chromosome 16p13 and replicates linkage with the metabolic syndrome on 3q27.

Prevalence of coronary heart disease (CHD), of type 2 diabetes (T2DM) and of the metabolic syndrome are in Mauritius amongst the highest in the world. As T2DM and CHD are closely associated and have both a polygenic basis, we conducted a 10 cM genome scan with 403 microsatellite markers in 99 independent families of North-Eastern Indian origin including 535 individuals. Families were ascertained through a proband with CHD before 52 years of age and additional sibs with myocardial infarction (MI) or T2DM. Model-free two-point and multipoint linkage analysis were performed using the Mapmarker-Sibs (MLS) and maximum-likelihood-binomial (MLB) programs for autosomal markers and the Aspex program for chromosome X markers. In a second step, additional markers were studied to increase the genetic map density in three regions on chromosomes 3, 8 and 16 where initial indication for linkage was found. Our data show suggestive linkage with CHD on chromosome 16p13-pter with the MLS statistics at 8.69 cM (LOD = 3.06, P = 0.00017) which partially overlaps with a high pressure (HBP) peak. At the same locus, a nominal indication for linkage with T2DM was found in 35 large T2DM Pondicherian families also having Indian origin. With respect to region 8q23, we found suggestive linkage with T2DM (LOD = 2.55, P = 0.00058) as well as with HBP. On 3q27, we replicated previous indication for linkage found in Caucasians (for the metabolic syndrome and for diabetes) according to the categorized trait for CHD and MI with the MLB statistics (LOD = 2.13, P = 0.0009). The genome scan also revealed nominal evidence of linkage with CHD on 10q23 (LOD = 2.06, P = 0.00188). Interestingly, we detected in the same region overlapping linkages with three QTLs: age of onset of CHD (LOD = 2.03), HDL cholesterol (LOD = 1.48) and LDL/HDL ratio (LOD = 1.34). Ordered-subset analysis based on family body mass index ranking replicated finding on 2q37 for T2DM (at Calpain 10 locus). These results show the first evidence for susceptibility loci that predispose to CHD, T2DM and HBP in the context of the metabolic syndrome.

Chromosome Mapping↗

PubMed2025

Genome-wide analysis of screen behaviors among adolescents identifies novel loci and overlap with educational attainment and mental disorders.

Technological devices play a central role in adolescents' life. Despite concerns about negative effects of excessive screen time, there is little knowledge of screen behaviors' genetic architecture. Using self-reports from adolescents in the Norwegian Mother, Father, and Child Cohort Study (n = 18,490), we performed genome-wide association analysis for four screen behaviors: time spent (1) watching television; (2) gaming; (3) sitting/lying down with a screen device; and (4) using social media. The resulting summary statistics were analysed using the conditional false discovery rate (condFDR) approach to increase genetic discovery. We also estimated SNP-heritabilities of the screen behaviors and genetic correlations with eight psychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder, attention-deficit hyperactivity disorder, anorexia nervosa, cannabis use disorder and alcohol use disorder), and educational attainment. Screen behaviors displayed significant SNP-heritabilities (0.048-0.12). We observed significant genetic correlations between screen behaviors and psychiatric disorders (rg range: 0.21-0.42). Educational attainment demonstrated negative genetic correlation with screen behaviors, most strongly with social media use (rg = - 0.69). CondFDR analysis identified three novel loci associated with social media use. Thus, we show that screen behaviors are heritable, polygenic traits that partly share genetic signal with mental disorders and educational attainment.

Humans↗

PubMed1999

Commentary on Annett, Yeo et al., Klar, Saugstad and Orr: cerebral asymmetry, language and psychosis--the case for a Homo sapiens-specific sex-linked gene for brain growth.

Annett, Yeo et al. and Klar have each proposed theories that relate the genetics of cerebral lateralization to predisposition to psychosis. These theories are considered in relation to the central paradox that psychosis is associated with a substantial biological disadvantage. Annett's heterozygote advantage hypothesis critically identified lateralization as a major determinant of ability, but it appears that what is inherited is degrees (as suggested by Yeo et al.) rather than (or as well as) direction of lateralization. Relative hand skill has been shown (Crow, T.J., Crow, L.R., Done, D.J., Leask, S.J., 1998. Relative hand skill predicts academic ability: global deficits at the point of hemispheric indecision. Neuropsychologia 36, 1275-1282.) to be a powerful predictor (interacting with sex) of academic ability but the greatest region of vulnerability (that includes reading disability and predisposition to psychosis) is close to the point of equal hand skill ('hemispheric indecision'). In contrast with Annett's single locus, Yeo's polygenic and Klar's strand-segregation hypotheses, each of which postulates an autosomal locus or loci, the hypothesis of a single gene for asymmetry located in a sex-specific region of homology on both X and Y chromosomes can account for sex differences, as observed in age of onset, and premorbid precursors of psychosis, as well as differences in the general population in relation to degrees of hand skill, verbal ability and cerebral asymmetry. The evolutionarily recent transposition to, and subsequent paracentric inversion in, the Y chromosome short arm of a 4-Mb block from Xq21.3 (the proximal long arm of the X) are candidates for speciation events in the lineage that led to Homo sapiens. A gene associated with a range of variation (that may be due to a high mutation site, or perhaps to epigenetic modification) on the Y that overlaps with, but differs quantitatively from, that on the X may explain the sex differences associated with psychosis, and may be relevant to its persistence. Such a gene could be the principal determinant in Man of the rate of brain growth, as suggested by Saugstad and by the findings of a recent study of adolescent onset psychosis (James, A., Crow, T.J., Renowden, S., Wardell, M., Smith, D.M., Anslow, P., in press. Is the course of brain development in schizophrenia delayed? Evidence from onsets in adolescence. Schizophr. Res.).

Biological Evolution↗

PubMed2026

Beyond years of schooling: Genetic associations across educational milestones in two Norwegian cohorts.

Although educational attainment is heritable, years-of-education (EduYears) measures are not designed to show how genetic associations vary across discrete educational milestones. In the Norwegian Mother, Father and Child Cohort Study (MoBa; N = 120,527) and the Norwegian Twin Registry (N = 8,910), we combined genome-wide association studies (GWAS), polygenic indices (PGIs), and twin models to characterize genetic associations with high-school completion and bachelor's, master's, and doctoral attainment. In transition-specific analyses conditional on prior attainment, observed-scale common-variant heritability (h2SNP) and PGI discrimination followed an inverse-U pattern, peaking for progression from high-school completion to attainment of at least a bachelor's degree (HS → BSc + ; h2SNP ≈ 0.14; R2Tjur ≈ 0.05) and declining at postgraduate transitions. Genetic correlations (rg) with large-scale GWAS of EduYears (EA4) and intelligence were high at earlier transitions but lower at later ones (for EA4, rg ≈ 0.92 at HS → BSc+ and ≈ 0.38 at MSc → PhD). In cumulative analyses of attained status in the full cohort, the point-estimate gap between twin- and SNP-based heritability narrowed from ≈ 0.38 at high-school completion to ≈ 0.11 at PhD, while genetic overlap was lower for distant than adjacent milestones (rg ≈ 0.71 for high-school completion versus PhD and ≈ 0.92 for adjacent milestones). Sensitivity analyses using an alternative intelligence GWAS and additional PGIs showed similar transition-specific trajectories. At the doctoral transition, estimates were obtained among individuals who had attained at least a master's degree, so attenuation there must be interpreted in light of selection and range restriction. Because EduYears converts distinct credentials and progression steps into a single numerical scale, estimates expressed per additional year should not be interpreted as though one year has the same meaning across the educational sequence. Milestone-preserving analyses make that hidden structure visible and sharpen the interpretation of education GWAS and PGIs.

Journal Article↗

PubMed2003

Effects of including a quantitative trait locus in selection under different waiting plans of young bulls.

The advantage of using the genotype of a quantitative trait locus (QTL) in selection schemes of dairy cattle was quantified using stochastic simulation. Three selection plans were studied. In the first plan, young bulls waited for 3 yr until their sisters completed a lactation and then were evaluated and selected based on an animal model. In a second plan, young bulls waited for 5 yr until their daughters completed a lactation. An intermediate 4-yr waiting plan was also studied. Simulation was for 16 yr with overlapping generations. Population and model parameters were proportional to the U.S. Holstein population. The advantage of using a QTL was quantified as the percentage of superiority of QTL-assisted over QTL-free selection using cumulative genetic response. Percentage of superiority was reported for four selection pathways: active sires, young bulls, bull dams, and first lactation cows. A general trend was observed: low superiority in early years of selection that increased to a plateau in later years and then decreased. The superiority of the QTL information was greatest in the 3-yr waiting plan and least in the 4-yr waiting plan. Superiority at plateau for selection pathways ranged from 16 to 26% for the 3-yr waiting plan, from 3 to 12% for the 4-yr waiting plan, and from 5 to 13% for the 5-yr waiting plan. The contribution to selection response attributed to the QTL and the polygenes was quantified. The rate at which the favorable allele approached fixation and the accuracy of predicting breeding values on the percentage of superiority were studied.

Animals↗

PubMed1990

Multigenic human hypertension: evidence for subtypes and hope for haplotypes.

Hypertension that occurs before the age of 60 years is strongly aggregated in families, mostly due to genetic factors with weaker contributions from a shared family environment. Hypertension is probably a heterogeneous collection of overlapping subsets of pathophysiological mechanisms, such as dyslipidemia, obesity, hyperinsulinemia and cation metabolism. Highly heritable traits such as sodium-lithium countertransport, urinary kallikrein excretion and a body fat pattern index show evidence of major gene segregation in families with hypertension. They are thought to be intermediate phenotypes in the chain of pathophysiological events leading from specific genes to the distant phenotype of hypertension. They provide evidence of measurable contributions from single gene traits to the susceptibility to hypertension. Genetic linkage studies have suggested that other specific loci (e.g. histocompatibility leukocyte antigen, blood group MN and the haptoglobin protein) contribute to the susceptibility to hypertension. DNA sequencing has shown a point mutation for lipoprotein lipase that conveys susceptibility to lipid abnormalities, and possibly also hypertension, as seen in families with dyslipidemic hypertension. Further application of these approaches, especially in families that include multiple siblings with hypertension, shows promise of a true understanding of how the combined effects of a few specific genes, the polygenic background and selected environmental factors can lead to essential hypertension. This understanding should foster better tailored and more effective approaches to the prevention, diagnosis and treatment of hypertension.

Blood Pressure↗

PubMed2025

Genetic relationships between systemic lupus erythematosus and a positive antinuclear antibody test in the absence of autoimmune disease.

OBJECTIVE: We defined the genetic factors associated with a positive ANA test (ANA+) in the absence of autoimmune disease and tested the association with SLE. METHODS: Using a case-control design, we performed a genome-wide association study (GWAS) in individuals of European ancestry without an autoimmune disease who had ANA tested as part of clinical care from DNA biobanks linked to de-identified electronic medical records: BioVU and Electronic Medical Records and Genomics. GWAS results were meta-analysed and single nucleotide polymorphism (SNP) heritability was calculated. A polygenic risk score (PRS) for ANA+ and for SLE was constructed and compared in patients with SLE, ANA+ and ANA negative (ANA-) individuals without autoimmune disease and general controls who never had ANA testing performed. RESULTS: A total of 7287 individuals of European ancestry were included in the meta-analyses (2169 ANA+ and 5118 ANA-); an SNP upstream of the TSBP1 in the HLA locus (rs1967688) was associated with ANA+ (p=4.84×10-8). SNP heritability for ANA+ was low (h2 SNP= 0.04), and the PRS for ANA+ was not significantly different in ANA+ and ANA- individuals. In contrast, the PRS for SLE was significantly higher in SLE compared with ANA+ individuals (p<2.2×10-16) but did not differ among ANA+, ANA- and general control groups (p=0.17). CONCLUSIONS: ANA+ occurring in the absence of autoimmune disease has a genetic association with the HLA region, but overall heritability is low. In addition, few SLE-associated SNPs were associated with ANA+, and the PRS for SLE was not associated with ANA+, indicating limited genetic overlap.

Humans↗

PubMed2004

Risk of wrist fracture in women is heritable and is influenced by genes that are largely independent of those influencing BMD.

UNLABELLED: Using a classical twin design study, we estimated the genetic contribution to liability of wrist fracture in women to be statistically and clinically significant. BMD is highly heritable, but statistical models showed very little overlap of shared genes between the two traits. INTRODUCTION: Studies have observed contradictory evidence for genetic effects influencing the outcome of osteoporotic fracture, in part because of the methodological problems involved in analyzing age-related "censored" outcomes. Although a shared genetic etiology is often assumed between fracture and low BMD, this has not been shown to be the case. MATERIALS AND METHODS: In a study of 6570 white healthy female volunteer twins between 18 and 80 years of age, we identified and validated 220 nontraumatic wrist fracture cases. From this we estimated the population prevalence, case-wise twin concordance, heritability in liability to wrist fracture (WF), and the genetic contribution to WFs controlling for age by analyzing the survival outcome using generalized linear mixed models implemented in Winbugs software. We included forearm BMD as a co-variate in some of the models to test whether there is a shared genetic etiology between WFs and BMD. RESULTS: The prevalence of WFs in women was estimated to be 3.3% with a case-wise concordance in monozygotic twins of 0.28 and 0.11 in dizygotic twins. The additive polygenic heritability in liability was approximately 54%, and a significant genetic etiology was confirmed by analyzing WFs as a survival outcome. The magnitude of the genetic influence on risk of WFs reduced very little when BMD was included as a co-variate in the survival analysis model. CONCLUSIONS: There is an important genetic contribution to the risk of WFs, but for the most part, these genes are unlikely to play a direct etiological role in the development of low BMD. If these results are confirmed for other sites, fracture and low BMD will have their own specific genetic risk factors that are unlikely to be shared between the two traits. This has important clinical and research implications.

Adolescent↗

PubMed2002

A novel susceptibility locus on chromosome 2 in the (New Zealand Black x New Zealand White)F1 hybrid mouse model of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is inherited as a complex polygenic trait. (New Zealand Black (NZB) x New Zealand White (NZW)) F(1) hybrid mice develop symptoms that remarkably resemble human SLE, but (NZB x PL/J)F(1) hybrids do not develop lupus. Our study was conducted using (NZW x PL/J)F(1) x NZB (BWP) mice to determine the effects of the PL/J and the NZW genome on disease. Forty-five percent of BWP female mice had significant proteinuria and 25% died before 12 mo of age compared with (NZB x NZW)F(1) mice in which >90% developed severe renal disease and died before 12 mo. The analysis of BWP mice revealed a novel locus (chi(2) = 25.0; p < 1 x 10(-6); log of likelihood = 6.6 for mortality) designated Wbw1 on chromosome 2, which apparently plays an important role in the development of the disease. We also observed that both H-2 class II (the u haplotype) and TNF-alpha (TNF(z) allele) appear to contribute to the disease. A suggestive linkage to proteinuria and death was found for an NZW allele (designated Wbw2) telomeric to the H-2 locus. The NZW allele that overlaps with the previously described locus Sle1c at the telomeric part of chromosome 1 was associated with antinuclear autoantibody production in the present study. Furthermore, the previously identified Sle and Lbw susceptibility loci were associated with an increased incidence of disease. Thus, multiple NZW alleles including the Wbw1 allele discovered in this study contribute to disease induction, in conjunction with the NZB genome, and the PL/J genome appears to be protective.

Alleles↗

PubMed2006

Evidence for involvement of the vitamin D receptor gene in idiopathic short stature via a genome-wide linkage study and subsequent association studies.

Stature is a highly heritable trait under both polygenic and major gene control. We aimed to identify genetic regions linked to idiopathic short stature (ISS) in childhood, through a whole genome scan in 92 families each with two affected children with ISS, including constitutional delay of growth and puberty and familial short stature. Linkage analysis was performed for ISS, height and bone age retardation. Chromosome 12q11 showed significant evidence of linkage to ISS and height (maximum non-parametric multipoint LOD scores 3.18 and 2.31 at 55-58 cM, between D12S1301 and D12S1048), especially in sister-sister pairs (LOD score of 1.9 for ISS in 22 pairs). These traits were also linked to chromosomes 1q12 and 2q36. The region on chromosome 12q11 had previously shown significant linkage to adult stature in several genome scans and harbors the vitamin D receptor gene, which has been associated with variation in height. A single nucleotide polymorphism (SNP) (rs10735810, FokI), which leads to a functionally relevant alteration at the protein level, showed preferential transmission of the transcriptionally more active G-allele to affected children (P=0.04) and seems to be responsible for the observed linkage (P=0.05, GIST test). Bone age retardation showed moderate linkage to chromosomes 19p11-q11 and 7p14 (LOD scores 1.69 at 57 cM and 1.42 at 50 cM), but there was no clear overlap with linkage regions for stature. In conclusion, we identified significant linkage, which might be due to a functional SNP in the vitamin D receptor (VDR) gene and could be responsible for up to 34% of ISS cases in the population.

Adolescent↗

PubMed2003

Genetic markers of disease susceptibility and severity in giant cell arteritis and polymyalgia rheumatica.

BACKGROUND AND OBJECTIVES: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are common and often overlapping diseases that generally occur in elderly patients. In this article, we examine the role of different genes as markers of disease susceptibility and severity in GCA and PMR. METHODS: The influence of human leukocyte antigen (HLA)-DRB1 and tumor necrosis factor alleles, as well as the different allelic polymorphisms, on the susceptibility and severity to GCA and PMR was examined. A review of the literature was conducted. RESULTS: Most studies have described an association of GCA with HLA-DRB1(*)04 alleles. However, HLA-DRB1 association in patients with PMR varies from one population to another. In Northwest Spain, patients with GCA and PMR exhibited different tumor necrosis factor microsatellite polymorphism associations. Studies of intercellular adhesion molecule-1 biallelic polymorphisms have yielded contradictory results. Interleukin 1 cluster and tumor necrosis factor alpha polymorphisms increased susceptibility to GCA and PMR slightly. In Northwest Spain, interleukin 6 promoter polymorphism at position -174 modulated the phenotypic expression of PMR in biopsy-proven GCA. In the same population, regulated upon activation, normal T cell expressed and presumably secreted gene promoter biallelic polymorphism at position -403 was a marker for PMR susceptibility but not for GCA, and corticotropin-releasing hormone polymorphism appeared to be implicated in the risk of severe ischemic complications in patients with GCA. CONCLUSIONS: The present analysis confirms that GCA and PMR are polygenic diseases. The search for additional genes is necessary to better understand the pathogenesis of these conditions.

Animals↗

PubMed2026

Integrative post-GWAS analysis prioritizes immune regulatory pathways and candidate effector signals in systemic lupus erythematosus.

BACKGROUND: Systemic lupus erythematosus (SLE) has a complex polygenic architecture, but translating genome-wide association signals into biologically interpretable candidates remains challenging. We applied an integrative post-GWAS framework to refine SLE-associated loci and prioritize candidate regulatory mechanisms. METHODS: European-ancestry SLE GWAS summary statistics from FinnGen and Bentham et al. were meta-analysed, comprising 8417 cases and 354,277 controls. After quality filtering, 6,782,131 SNPs were retained. Downstream analyses included LAVA regional prioritization, Bayesian colocalization with GTEx v8 whole-blood and spleen eQTLs, independent replication in the Julià et al. Spanish cohort, pathway enrichment, bivariate LAVA cross-trait local genetic correlation, and therapeutic annotation. RESULTS: The discovery meta-analysis identified 46 genome-wide significant SLE-associated loci, including putative novel signals requiring database/literature qualification. LAVA identified 14 candidate index variants across 12 high-confidence regions, of which nine index variants were retained as the primary prioritized set based on LAVA support and/or convergent regulatory evidence. The strongest association mapped to the chr6p21.3/MHC region (rs389884), where four genes showed colocalization support, including CLIC1 in whole blood and C4A in spleen. Because the chr6p21.3/MHC rs389884 region lead variant was unavailable for replication and no suitable proxy was identified, this signal was interpreted as an emerging candidate for functional validation rather than a replicated causal signal. Seven available variants replicated with concordant effects. An exploratory Roadmap immune chromatin-state overlap analysis placed 15 of 45 non-MHC lead variants (33.3%) directly, and 34 of 45 (75.6%) within ±10 kb, in active immune enhancer/promoter states. Pathway analyses highlighted type I interferon, JAK-STAT signaling, cytokine regulation, and antigen presentation, while bivariate LAVA analyses supported shared local genetic architecture with rheumatoid arthritis, systemic sclerosis, and Sjögren syndrome. CONCLUSIONS: This integrative post-GWAS analysis refines SLE association signals into biologically interpretable candidate regions and supports interferon and JAK-STAT signaling as central genetically supported pathways in SLE.

CLIC1↗

PubMed2026

From gut to pancreas: Shared genetic susceptibility and biological convergence in acute pancreatitis and Crohn's disease.

BACKGROUND: Acute pancreatitis (AP) and Crohn's disease (CD) exhibit overlapping clinical presentations and an unexpectedly high rate of comorbidity. Whether this reflects shared genetic susceptibilities remains unclear. METHODS: We performed a cross-trait genome-wide association analysis leveraging European-ancestry summary statistics for AP (Ncases = 8446; Ncontrols = 437,418) and CD (Ncases = 12,194; Ncontrols = 28,072). Firstly, cross-trait genetic correlation was estimated using linkage disequilibrium score regression (LDSC) and high-definition likelihood (HDL). Secondly, to pinpoint specific pleiotropic loci and prioritize candidate genes, we employed PLACO under a rigorous composite null hypothesis, integrated with Bayesian colocalization and SMR/HEIDI analyses. Finally, we dissected the underlying biological context by mapping tissue-specific regulatory enrichment and pathway convergence using FUMA, MAGMA, and Stratified LD Score Regression (S-LDSC). RESULTS: AP and CD showed significant positive genetic correlation (LDSC: rg = 0.178, SE = 0.079, P = 0.025; HDL: rg = 0.294, SE = 0.096, P = 0.0021). Pleiotropy analyses revealed 86 SNPs and 6 independent genome-wide significant pleiotropic loci (lead variants at 5q33.1, 6q22.33, 7q34, 10q24.2, 15q22.33 and 19q13.11, PPLACO < 5 × 10-8). Colocalization showed suggestive evidence of a shared causal signal at 6q22.33 (PP4 = 0.666). Gene-based tests of the AP-CD cross-trait statistics prioritized eight pleiotropic genes-RSPO3, ATG16L1, SMAD3, FADS1, ZPBP2, FADS2, PRKAA1 and IRGM. Gene-set analyses highlighted IL-23/Th17-related and broader inflammatory response pathways. CONCLUSIONS: AP and CD share polygenic susceptibility and converge on immune and inflammatory processes, with prioritized genes pointing to autophagy, lipid metabolism and TGF-β/SMAD-related biology.

Humans↗