Full Siblings Research Articles

Genetic Control of Pitch Canker Response in Southern Pine and Southern Pine Hybrids

Fusarium circinatum causes pine pitch canker (PPC) disease and associated symptoms such as resinous lesions, mechanical weakness, and crown dieback that may lead to mortality in Pinus and Pseudotsuga spp. There are no ameliorative techniques available for the disease, and the genetic resistance among populations to support commercial plantation deployment has not been well characterized. In this study, we characterize the genetic control of PPC disease tolerance (and/or resistance) and predict the tolerance of families in existing breeding populations: open-pollinated (OP) half-sib and control-pollinated full-sib (FS) slash pine (Pinus elliottii var. elliottii Engelm.), OP loblolly pine (Pinus taeda L.), and advanced-generation OP hybrid slash × P. caribaea (Pinus elliottii var. elliottii Engelm. × Pinus caribaea var. bahamensis, caribaea, and hondurensis) using F. circinatum isolates obtained from three locations in Georgia and FL, USA. We describe a new experimental design that improves the accuracy of breeding value predictions, provides more precise genetic parameter estimates, and facilitates comparisons within and among taxa as well as comparisons among isolates. We found strong evidence for genetic control of the ratio of stem damage by F. circinatum, especially in slash pine and slash × P. caribaea hybrids. Loblolly and slash × P. caribaea hybrids exhibited less damage than slash pine. We observed a spectrum of virulence among F. circinatum isolate sources, which were not equally virulent in different pine taxa.

Comorbidities in autism spectrum disorder and their etiologies

Individuals with autism spectrum disorder (ASD), in addition to the core features of the disease, experience a higher burden of co-occurring medical conditions. This study sought to describe the frequency and distribution of comorbidit conditions in individuals with ASD, and systematically evaluate the possibility that pre- and postnatal exposures (e.g., preterm birth, hypoxia at birth, traumatic brain injury, and fetal alcohol syndrome) associated with ASD may also be linked with distinct comorbidities. We used the SPARK study database, launched by the Simons Foundation Autism Research Initiative (SFARI). Comorbidities considered in the study included neurological, cognitive, psychiatric, and physical conditions. The study sample consisted of 42,569 individuals with ASD and their 11,389 non-ASD siblings (full and half siblings). Majority (74%) of individuals with ASD had at least one comorbidity, and had a greater average number of comorbidities than their non-ASD siblings. Preterm birth and hypoxia at birth were the most common peri-natal exposures in the sample. In logistic regression models adjusted for covariates, these exposures were associated with several distinct comorbidities in ASD cases, including attention and behavior problems, psychiatric and neurological disorders, and growth conditions. A similar pattern of association was also observed in non-ASD siblings. Our findings underscore that individuals with ASD experience a greater burden of comorbidities, which could be partly attributable to the higher rates of perinatal exposures compared to their non-ASD siblings. Study findings, if replicated in other samples, can inform the etiology of comorbidity in ASD.

Long-term risk of inflammatory bowel disease after endoscopic biopsy with normal mucosa: A population-based, sibling-controlled cohort study in Sweden.

Although evidence suggests a persistently decreased risk of colorectal cancer for up to 10 years among individuals with a negative endoscopic biopsy result (i.e., normal mucosa), concerns have been raised about other long-term health outcomes among these individuals. In this study, we aimed to explore the long-term risk of inflammatory bowel disease (IBD) after an endoscopic biopsy with normal mucosa. In the present nationwide cohort study, we identified all individuals in Sweden with a lower or upper gastrointestinal (GI) biopsy of normal mucosa during 1965 to 2016 (exposed, n = 200,495 and 257,192 for lower and upper GI biopsy, respectively), their individually matched population references (n = 989,484 and 1,268,897), and unexposed full siblings (n = 221,179 and 274,529). Flexible parametric model estimated hazard ratio (HR) as an estimate of the association between a GI biopsy of normal mucosa and IBD as well as cumulative incidence of IBD, with 95% confidence interval (CI). The first 6 months after GI biopsy were excluded to avoid detection bias, surveillance bias, or reverse causation. During a median follow-up time of approximately 10 years, 4,853 individuals with a lower GI biopsy of normal mucosa developed IBD (2.4%) compared to 0.4% of the population references. This corresponded to an incidence rate (IR) of 20.39 and 3.39 per 10,000 person-years in the respective groups or 1 extra estimated IBD case among 37 exposed individuals during the 30 years after normal GI biopsy. The exposed individuals had a persistently higher risk of overall IBD (average HR = 5.56; 95% CI: 5.28 to 5.85), ulcerative colitis (UC, average HR = 5.20; 95% CI: 4.85 to 5.59) and Crohn's disease (CD, average HR = 6.99; 95% CI: 6.38 to 7.66) than their matched population references. In the sibling comparison, average HRs were 3.27 (3.05 to 3.51) for overall IBD, 3.27 (2.96 to 3.61) for UC, and 3.77 (3.34 to 4.26) for CD. For individuals with an upper GI biopsy of normal mucosa, the average HR of CD was 2.93 (2.68 to 3.21) and 2.39 (2.10 to 2.73), compared with population references and unexposed full siblings, respectively. The increased risk of IBD persisted at least 30 years after cohort entry. Study limitations include lack of data on indications for biopsy and potential residual confounding from unmeasured risk or protective factors for IBD. Endoscopic biopsy with normal mucosa was associated with an elevated IBD incidence for at least 30 years. This may suggest a substantial symptomatic period of IBD and incomplete diagnostic examinations in patients with early IBD.

Genetic analyses reveal promiscuous mating in female common minke whales, Balaenoptera acutorostrata

Based on 25 microsatellites, first order relatedness was established for three dyads of individuals contained in the Norwegian minke whale DNA-register. One large female minke whale was a member of all three dyads. Two competing genealogies were considered and under both of these the quartet contained siblings that with high probability must be half-siblings, as opposed to being full siblings.

Familial Associations of Complete Atrioventricular Block: A National Family Study in Sweden.

Complete atrioventricular block (CAVB) is a major reason for implantation of permanent pacemakers, but knowledge of CAVB inheritance is sparse. This nationwide study aimed to determine the occurrence of CAVB in first-, second-, and third-degree relatives (full siblings, half-siblings, and cousins). The Swedish multigeneration register was linked to the Swedish nationwide patient register for the period 1997 to 2012. All Swedish full sibling, half-sibling, and cousin pairs born to Swedish parents between 1932 and 2012 were included. Competing risks and time-to-event, subdistributional hazard ratios (SHRs) according to Fine and Gray and hazard ratios using Cox proportional hazards model were estimated using robust SEs and considering the relatedness of relatives (full siblings, half-siblings, cousins). Additionally, odds ratios (ORs) for CAVB were calculated for traditional cardiovascular comorbidities. The study population (N=6 113 761) consisted of 5 382 928 full siblings, 1 266 391 half-siblings, and 3 750 913 cousins. In total, 6442 (0.11%) unique individuals were diagnosed with CAVB. Of these, 4200 (65.2%) were males. SHRs for CAVB were 2.91 for full siblings (95% CI, 2.43-3.49), 1.51 for half-siblings (0.56-4.10), and 3.54 for cousins (1.73-7.26) of affected individuals. Age-stratified analysis showed higher risk in young individuals born from 1947 to 1986: SHR, 5.30 (3.78-7.43) for full siblings, SHR, 3.30 (1.06-10.31) for half-siblings, and SHR, 3.15 (1.39-7.17) for cousins. Similar familial HRs according to Cox proportional hazard model and ORs were obtained without any major differences. Apart from familial relationship, CAVB was associated with hypertension (OR, 1.83), diabetes (OR, 1.41), coronary heart disease (OR, 2.08), heart failure (OR, 5.01), and structural heart disease (OR, 4.59). Risk of CAVB among relatives of affected individuals depends on relationship degree, being strongest in young siblings. The familial association extending to third-degree relatives indicates presence of genetic components in the cause of CAVB.

Association of inflammatory bowel disease in first-degree relatives with risk of colorectal cancer: A nationwide case-control study in Sweden.

This study aims to assess the association between inflammatory bowel disease (IBD) history in first-degree relatives (FDRs) and colorectal cancer (CRC) risk. We conducted a nationwide case-control study in Sweden among 69 659 CRC cases and 343 032 non-CRC controls matched on age, sex, birth year and residence county. Through linkage of multi-generation register and the nationwide ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) cohort, we ascertained IBD diagnoses among parents, full siblings and offspring of the index individuals. Odds ratios (ORs) of CRC associated with IBD family history were calculated using conditional logistic regression. 2.2% of both CRC cases (1566/69659) and controls (7676/343027) had ≥1 FDR with IBD history. After adjusting for family history of CRC, we observed no increased risk of CRC in FDRs of IBD patients (OR, 0.96; 95%CI, 0.91-1.02). The null association was consistent according to IBD subtype (Crohn's disease or ulcerative colitis), number of FDRs with IBD (1 or ≥ 2), age at first IBD diagnosis in FDRs (<18, 18-39, 40-59 or ≥60 years), maximum location/extent of IBD or FDR relation (parent, sibling or offspring). The null association remained for early-onset CRC (diagnosed at age <50 years). In conclusion, IBD history in FDRs was not associated with an increased risk of CRC. Our findings suggest that extra screening for CRC may not be needed in the offspring, siblings or parents of IBD patients, and strengthen the theory that it is the actual inflammation or atypia of the colon in IBD patients that confers the increased CRC risk.

Association of Familial Aggregation of Major Depression With Risk of Major Depression

Major depression (MD) aggregates within families, but how family history of MD confers risk of MD over the life course is unclear. Such knowledge is important to identify and prevent possible depressogenic effects of family environment. To examine the association between family MD history and risk of MD including association with age, sex, type of kinship, and age of the affected family member. This cohort study included all Danish citizens born from 1960 to 2003 with known parental identity followed up from their 15th birthday until time of MD, censoring, or December 31, 2018. Analysis took place between April 2022 and December 2022. Family members with first-time MD using International Classification of Diseases, Eighth Revision codes 296.09, 296.29, 298.09, and 300.49 or 10th Revision codes F32.0-F33.9, family members' age at MD onset, and individuals' age at exposure to family MD. Multivariable Poisson regression was applied to estimate the incidence rate ratio (IRR) with 95% CI of first-time MD. Of 2 903 430 individuals (1 486 574 [51.2%] men), 37 970 men (2.6%) and 70 223 women (5.0%) developed MD during follow-up. For men, exposure to maternal, paternal, or full sibling MD were associated with a 2-times higher risk of MD (IRR, 2.10 [95% CI, 2.02-2.19]; IRR, 2.04 [95% CI, 1.94-2.14]; IRR, 2.08 [95% CI, 1.97-2.19]) and the associated risk increased with number of affected family members. This pattern was similar for women. For men, family members' age at MD onset was not associated with MD. For women, maternal MD onset at 69 years or younger was associated with higher IRRs of MD (age <40 years: IRR, 1.64 [95% CI, 1.28-2.10]; age 40-49 years: IRR, 1.62 [95% CI, 1.27-2.07]; age 50-59 years: IRR, 1.56 [95% CI, 1.22-2.00]; and age 60-69 years: IRR, 1.67 [95% CI, 1.28-2.16]) compared with women with maternal MD onset at 70 years or older. For men, exposure to maternal MD younger than 30 years (age <1 year: IRR, 1.95 [95% CI, 1.70-2.25]; age 1 to <12 years: IRR, 2.31 [95% CI, 2.16-2.47]; age 12 to <19 years: IRR, 2.18 [95% CI, 2.03-2.35]; age 19 to <30 years: IRR, 1.42 [95% CI, 1.32-1.53]) was associated with increased IRRs, while exposure to maternal MD at 30 years or older was associated with a lower IRR (0.77 [95% CI, 0.70-0.85]). The findings were similar across type of kinships and for women. In this study, risk of MD was associated with increased numbers of affected family members but did not vary by gender or type of kinship. Exposure to family MD during childhood and adolescence was associated with increased risk.

Gestational age at birth and cognitive outcomes in adolescence: population based full sibling cohort study

ObjectiveTo investigate the association between gestational age at birth and cognitive outcomes in adolescence.DesignNationwide population based full sibling cohort study.SettingDenmark.Participants1.2 million children born between 1 January 1986 and 31 December...

An analysis of data curated from 5 years of identifying human remains.

An archive of 5 years of cases involving the identification of human remains was curated, collecting information on: The sample type submitted, the number of STR loci yielding interpretable results, the kinship challenge posed, and the outcome for the case. A total of 129 cases of remains ID were investigated using manual DNA extraction and recovery methods with amplification of STR markers using the Power Plex 21 multiplex STR kit from Promega Corp. In 52 cases, blood spots collected by the ME were provided as sample and in 100% of those cases, probabilities of relatedness to the reference samples was ≥99%. In 77 cases, tissue other than blood was provided as a source of DNA. These other samples were grouped categorically into long bones (femur and tibia; 40 cases), skull bones/teeth (11 cases), other bones (16 cases), and tissue (normally adherent to bone) (10 cases). Reference samples provided for cases included alleged parents or child(ren) of the victim (86 cases), alleged full siblings of the victim (38 cases), or alleged second-order relatives (five cases). The overall success rate in confirming the identity of the source of the remains in these cases was 89.2%. Our results demonstrate that a laboratory can be often successful identifying human remains using methods easily implemented in any DNA typing laboratory.

Forensic efficiencies of individual identification, kinship testing and ancestral inference in three Yunnan groups based on a self-developed multiple DIP panel.

Deletion/insertion polymorphism (DIP), as a short insertion/deletion sequence polymorphic genetic marker, has attracted the attention of forensic genetic scientist due to its lack of stutter, short amplicon and abundant ancestral information. In this study, based on a self-developed 43 autosomal deletion/insertion polymorphism (A-DIP) loci panel which could meet the forensic application purposes of individual identification, kinship testing and ancestral inference to some extent, we evaluated the forensic efficiencies of the above three forensic objectives in Chinese Yi, Hani and Miao groups of Yunnan province. The cumulative match probability (CPM) and combined probability of exclusion (CPE) of these three groups were 1.11433E-18, 8.24299E-19, 4.21721E-18; 0.999610217, 0.999629285 and 0.999582084, respectively. Average 96.65% full sibling pairs could be identified from unrelated individual pairs (as likelihood ratios > 1) using this DIP panel, whereas the average false positive rate was 3.69% in three target Yunnan groups. With the biogeographical ancestor prediction models constructed by extreme gradient boosting (XGBoost) and support vector machine (SVM) algorithms, 0.8239 (95% CI 0.7984, 0.8474) of the unrelated individuals could be correctly divided according to the continental origins based on the 43 A-DIPs which were large frequency distribution differentiations among different continental populations. The present results of principal component analysis (PCA), multidimensional scaling (MDS), neighbor joining (NJ) and maximum likelihood (ML) phylogenetic trees and STRUCTURE analyses indicated that these three Yunnan groups had relatively close genetic distances with East Asian populations.

Multiple paternity in reproduction of European eel Anguilla anguilla (L. 1758) by artificial mixing of different sperm in equal volumes

Because of its complex life cycle and due to multiple stress factors, the European eel is suffering a dramatic decline and has been declared Critically Endangered by the IUCN. A possible way to address this problem could be relieve the pressure on natural stocks by implementing its mass production by artificial breeding protocols. A previous study based on direct observation and parentage assignment underlined the presence of an allegedly hierarchic structure among European eel males in semi-natural mating conditions, with a consequent bias in F1 proportion assigned to each one. The aim of the present study is to attest if a different fertilization protocol based on the artificial mixing of female eggs with different males’ milt in equal volume (1 F:4 M) could represent a solution to the disproportion observed in semi-natural conditions. For this purpose, six families of European eels were generated, and 10 species-specific microsatellite loci were used to infer offspring composition by paternity assignment on 280 samples. Due to the asynchronous ovarian development of female European eels, the percentage of fertilized eggs for each female showed a great variability, ranging from 4.70% to 94.50%. A proportion of 94.02% of genotyped offspring were assigned with high confidence to their true parents. As regard males’ fertilization pattern, no substantial differences from natural mating were observed: a single male accounted for most offspring, which was just mostly composed of full sibs. Concluding, the obtained results suggest that the admixture of an equal volume of different males’ milt seems to contribute to the single-locus genetic variability (observed heterozygosity higher than expected in 7 out 9 loci), but it is not sufficient to ensure all the males the same chance to transmit their gene pool, and new fertilization strategies must be developed.

Gender and age effects on dental and palatal arch dimensions among full siblings.

This study was conducted to investigate the dental and palatal arch dimensions of male and female siblings in relation to gender and age, using three-dimensional (3D) digital casts. This study involved 54 subjects (27 pairs) of male-female siblings aged 15 to 45 years. Dental casts were digitized and analyzed for tooth size (TS), arch width (AW), arch length (AL), arch length discrepancy (ALD), and palatal arch dimensions (PAD). The data obtained were subjected to t-tests, and the palatal curvature (PC) was modeled using a fourth-order polynomial. Significant differences (P < 0.05) between the sexes were found in the mesiodistal TS, particularly in all canines, as well as 16, 36, 46, and 41. Maxillary AW and AL were also significantly (P < 0.05) influenced by sexes. Most arch parameters were more prominent in male siblings, and the effect of age on PC differed between the sexes. In addition, the PC of adolescent females was mostly superimposed on adult females relative to males. Among siblings, males were found to have significantly larger dental arch dimensions than females. Furthermore, PC showed some differences between the sexes in both the frontal and sagittal planes.

Identification of novel SNP markers for kinship analysis in the Korean population

Kinship testing using genetic markers such as short tandem repeats (STRs) and single nucleotide polymorphisms (SNPs) is crucial for forensic analysis. Although STR markers have superior discriminatory power due to their highly polymorphic properties, they have several weak points in determining extended distant or complex relationships because of high mutation rates and low success rates in degraded samples. Therefore, SNPs are regarded as promising tools in forensic science because they have low mutation rates and small amplicon sizes. Herein, we propose an SNP panel consisting of 1400 autosomal SNPs obtained from the Korean National Standard Reference Variome (KoVariome) database. To evaluate its performance, in-silico analysis was performed using whole-genome sequencing (WGS) data from 21 Korean families. Subsequently, to estimate pairwise relatedness, kinship coefficients were calculated using PLINK, and Welch’s one-way ANOVA test with Games–Howell’s pairwise comparison test was performed. As a result, the average kinship coefficients of first- (parent–offspring and full siblings), second- (grandparent–grandchildren and aunt/uncle–niece/nephew), and third- (first cousin and grandniece/grandnephew) degree relatives, and unrelated were 0.24, 0.11, − 0.054, and − 0.0082, respectively. Consequently, relatives (first and second degree) were distinguished from non-relatives; however, further studies are required to investigate more effective SNP markers for discriminating extended kinship. Nevertheless, the results of this study go beyond the scope of screening using the discovered 1400 SNPs in Korean families and suggest the applicability of kinship analysis in the Korean population.

Utilizing a Population-Genetic Framework to Test for Gene-Environment Interactions between Zebrafish Behavior and Chemical Exposure.

Individuals within genetically diverse populations display broad susceptibility differences upon chemical exposures. Understanding the role of gene-environment interactions (GxE) in differential susceptibility to an expanding exposome is key to protecting public health. However, a chemical's potential to elicit GxE is often not considered during risk assessment. Previously, we've leveraged high-throughput zebrafish (Danio rerio) morphology screening data to reveal patterns of potential GxE effects. Here, using a population genetics framework, we apportioned variation in larval behavior and gene expression in three different PFHxA environments via mixed-effect modeling to assess significance of GxE term. We estimated the intraclass correlation (ICC) between full siblings from different families using one-way random-effects model. We found a significant GxE effect upon PFHxA exposure in larval behavior, and the ICC of behavioral responses in the PFHxA exposed population at the lower concentration was 43.7%, while that of the control population was 14.6%. Considering global gene expression data, a total of 3746 genes showed statistically significant GxE. By showing evidence that heritable genetics are directly affecting gene expression and behavioral susceptibility of individuals to PFHxA exposure, we demonstrate how standing genetic variation in a heterogeneous population such as ours can be leveraged to test for potential GxE.

Gastrointestinal biopsy of normal mucosa or nonspecific inflammation and risk of neurodegenerative disease: Nationwide matched cohort study.

Evidence has accumulated to support the early involvement of altered gastrointestinal (GI) function in neurodegenerative disease. However, risk of Alzheimer disease (AD) and Parkinson disease (PD) among individuals with a GI biopsy of normal mucosa or nonspecific inflammation is unknown. This matched cohort study included all individuals in Sweden with a GI biopsy of normal mucosa (n= 480,346) or nonspecific inflammation (n= 655,937) during 1965-2016 (exposed group) as well as their individually matched population references and unexposed full siblings. A flexible parametric model and stratified Cox model were used to estimate hazard ratio (HR) and its 95% confidence interval (CI). Individuals with normal mucosa or nonspecific inflammation had a higher risk of AD and PD during the 20 years after biopsy. Compared with the population references, individuals with normal mucosa had an increased risk of AD (incidence rate [IR] difference=13.53 per 100,000 person-years, HR [95% CI] = 1.15 [1.11-1.20]) and PD (IR difference=6.72, HR [95% CI] = 1.16 [1.10-1.23]). Elevated risk was also observed for nonspecific inflammation regarding AD (IR difference=13.28, HR [95% CI] = 1.11 [1.08-1.14]) and PD (IR difference=6.83, HR [95% CI] = 1.10 [1.06-1.14]). Similar results were observed in subgroup and sensitivity analyses and when comparing with their unexposed siblings. Individuals with a GI biopsy of normal mucosa or nonspecific inflammation had an increased risk of AD and PD. This adds new evidence of the early involvement of GI dysfunction in neurodegenerative disease.

Kinship and similarity drive coordination of breeding-group choice in male spotted hyenas.

When and where animals reproduce influences the social, demographic and genetic properties of the groups and populations they live in. We examined the extent to which male spotted hyenas (Crocuta crocuta) coordinate their breeding-group choice. We tested whether their propensity to settle in the same group is shaped by passive processes driven by similarities in their socio-ecological background and genotype or by an adaptive process driven by kin selection. We compared the choices of 148 pairs of same-cohort males that varied in similarity and kinship. We found strong support for both processes. Coordination was highest (70% of pairs) for littermates, who share most cumulative similarity, lower (36%) among peers born in the same group to different mothers, and lowest (7%) among strangers originating from different groups and mothers. Consistent with the kin selection hypothesis, the propensity to choose the same group was density dependent for full siblings and close kin, but not distant kin. Coordination increased as the number of breeding females and male competitors in social groups increased, i.e. when costs of kin competition over mates decreased and benefits of kin cooperation increased. Our results contrast with the traditional view that breeding-group choice and dispersal are predominantly solitary processes.

The mud-dwelling clam Meretrix petechialis secretes endogenously synthesized erythromycin

Although lacking an adaptive immune system and often living in habitats with dense and diverse bacterial populations, marine invertebrates thrive in the presence of potentially challenging microbial pathogens. However, the mechanisms underlying this resistance remain largely unexplored and promise to reveal novel strategies of microbial resistance. Here, we provide evidence that a mud-dwelling clam, Meretrix petechialis, synthesizes, stores, and secretes the antibiotic erythromycin. Liquid chromatography coupled with mass spectrometry, immunocytochemistry, fluorescence in situ hybridization, RNA interference, and enzyme-linked immunosorbent assay revealed that this potent macrolide antimicrobial, thought to be synthesized only by microorganisms, is produced by specific mucus-rich cells beneath the clam's mantle epithelium, which interfaces directly with the bacteria-rich environment. The antibacterial activity was confirmed by bacteriostatic assay. Genetic, ontogenetic, phylogenetic and genomic evidence, including genotypic segregation ratios in a family of full siblings, gene expression in clam larvae, phylogenetic tree, and synteny conservation in the related genome region further revealed that the genes responsible for erythromycin production are of animal origin. The detection of this antibiotic in another clam species showed that the production of this macrolide is not exclusive to M. petechialis and may be a common strategy among marine invertebrates. The finding of erythromycin production by a marine invertebrate offers a striking example of convergent evolution in secondary metabolite synthesis between the animal and bacterial domains. These findings open the possibility of engineering-animal tissues for the localized production of an antibacterial secondary metabolite.

Same-Sex Marriage and Common Mental Health Diagnoses: A Sibling Comparison and Adoption Approach

ABSTRACT We aimed to test whether the association between same-sex marriage and common mental health diagnoses was explained by shared genetic and environmental familial influences using sibling comparison and adoption analyses. For the sibling comparison analysis, participants (1,177,712 men and 1,266,917 women) were individuals born in Sweden between 1932 and 1994 and had ever been recorded as married (in opposite-sex or same-sex marriages). For the adoption analysis, participants were 147,164 and 1,298 female–female full sibling and adoptive sibling pairs, respectively. Based on medical records, prescribed medication, and death certificates, depression, substance abuse, and suicide (completed and attempted) from age 18 years were identified. For both sexes, being in a same-sex marriage was associated with greater risk of depression, substance abuse, and suicide, compared with being in an opposite-sex marriage. Controlling for shared familial confounding reduced this difference by less than 20% in magnitude, but overall mental health disparities for individuals in same-sex marriages remained statistically significant. Among women, only the genetic correlation between same-sex marriage and depression was statistically significant (r = .33). Same-sex marriage, as a proxy for sexual orientation, was associated with increased risk of certain mental health diagnoses and shared familial confounding explained a small component of this association, depending on the diagnosis. The findings indicate that sexual orientation disparities in mental health outcomes may involve unmeasured factors, and a relatively small proportion should be considered that may be due to shared familial confounding relevant to both sexual orientation and psychopathology.

LBODP030 A Rare Case Of Partial Lipodystrophy From Mpdl (mandibular Hypoplasia, Deafness, Progeroid, Lipodystrophy Syndrome) Due To Pold1 Gene Mutation

Abstract MDPL (Mandibular hypoplasia, Deafness, Progeroid, Lipodystrophy syndrome) caused by a mutation in the polymerase delta 1 (POLD1) gene is an extremely rare progeroid syndrome associated with partial lipodystrophy. Currently, there are about 24 cases reported worldwide(1), mostly in people of European descent. We are reporting one such rare case in a Hispanic patient. The patient is a 37 year old male from Honduras who was referred to us by genetics for diabetes management. Family members noted extremely thin limbs and he did not walk till 2 years of age. Family history was negative with 8 full siblings, all reportedly healthy. On examination, his BMI was 15.19 kg/m2. He was noted to have birdlike facies with mid-face hypoplasia, beaked nose, retrognathia, dental malocclusion, and protruding maxillary teeth. He also had bilateral proptosis. His extremities were thin, lacking subcutaneous fat and muscle bulk with distal joint contractures in elbow, hands and feet. Genitourinary showed low testicular volumes (&amp;lt;3 ml). Genetic testing revealed a recurring mutation in the active site of POLD1 gene, which is diagnostic for MDPL. His clinical presentation was classic with dysmorphism, deafness, lipodystrophy and metabolic abnormalities. Due to the rarity of the disorder, there is very limited data on management of these patients. A symptom-based management was recommended. In terms of his diabetes, it was diagnosed at age 33 when his HbA1c was 11.2 and he was started on insulin. Patients with this syndrome tend to have insulin resistance. C-peptide was 2.88 ng/ml (ref. range: 0.78 - 5.19 ng/mL) with glucose 160 mg/dL indicating adequate beta-cell reserve; GAD-65 and anti-pancreatic islet cell antibodies were negative. Insulin was weaned off and currently, his diabetes is being managed with diet and lifestyle changes. He was found to have elevated total cholesterol and triglycerides. Hepatic steatosis was seen on liver ultrasonography. He was started on fenofibrate and low-fat diet; lipid panel has normalized. His echocardiogram was normal. In addition, males are known to have hypogonadotropic hypogonadism however this patient had a low testosterone and high FSH and LH, indicative of primary hypogonadism. A scrotal ultrasound was ordered. DXA scan showed low bone mineral density with the lowest Z-score of -3.6 at the lumbar spine. He was started on testosterone replacement with Vitamin D. Testosterone therapy will help replace the testosterone deficiency in addition to slowing down bone loss. MDPL syndrome is an exceedingly rare clinical entity associated with multiple endocrinopathies. We plan to periodically monitor labs and imaging to continue managing this patient with a symptom-based approach. (1) Wang, Xiu-Wen; Lu, Ling-Yun; Xie, Ying1; Yu, Xi-Jie1 A Chinese girl with (MDPL) diagnosed via POLD1 mutation detection, Chinese Medical Journal: August 20, 2020 - Volume 133 - Issue 16 - p 2009-2011 Presentation: No date and time listed

REFERRAL FOR SUN ALLERGY – A CASE OF ERYTHROPOIETIC PROTOPORPHYRIA

<h3>Introduction</h3> Erythropoietic protoporphyria (EPP) is an inherited cutaneous porphyria characterized by painful, non-blistering photosensitivity usually noted in early childhood and occurring acutely after sunlight exposure. Cutaneous lesions develop within minutes of sun exposure with diffuse edema of the skin in sun-exposed areas, resembling angioedema. EPP is now recognized as the most common porphyria in children and the third most common in adults. In the review of over 100 cases in the United States, the average delay diagnosis of EPP was 13 years. <h3>Case Description</h3> A 29-year-old female with a PMH of polyglandular autoimmune disease presented to the Allergy clinic as a referral for "Sun Allergy". The patient reported a near lifelong history of a photosensitive rash. The rash typically begins 10-20 minutes after sun exposure, sparing covered areas. The rash is described as burning/stinging in nature, a 10/10 on the pain scale. She additionally reported intermittent, small bullae in affected areas. She denied pruritus and urticaria. Patient denied recent NSAID and antibiotic use. She denied the use of topicals, including sunscreen. Patient has one full sibling with a similar clinical course. Patient denied history of substance use disorder. Porphyria became the leading differential diagnosis. Serum porphyrins with reflex porphyrins were obtained and indicated elevated total serum porphyrins with notable reflex indicating elevated protoporphyrins. The patient was diagnosed with Erythropoietic Porphyria and referred to Dermatology for further management. <h3>Discussion</h3> This case highlights the importance of including porphyrias in the differential diagnosis of photosensitive rashes, which may be referred to Allergy and Immunology clinics for evaluation.