Paternal Family Research Articles

Reduced Mitochondria Cytochrome Oxidase Activity in Adult Children of Mothers with Alzheimer's Disease

Biomarker studies demonstrate inheritance of glucose hypometabolism and increased amyloid-β deposition in adult offspring of mothers, but not fathers, affected by late-onset Alzheimer's disease (LOAD). The underlying genetic mechanisms are unknown. We investigated whether cognitively normal (NL) individuals with a maternal history of LOAD (MH) have reduced platelet mitochondrial cytochrome oxidase activity (COX, electron transport chain complex IV) compared to those with paternal (PH) or negative family history (NH). Thirty-six consecutive NL individuals (age 55 ± 15 y, range 27-71 y, 56% female, CDR = 0, MMSE ≥28, 28% APOE-4 carriers), including 12 NH, 12 PH, and 12 MH, received a blood draw to measure platelet mitochondrial COX activity. Citrate synthase activity (CS) was measured as a reference. Groups were comparable for clinical and neuropsychological measures. We found that after correcting for CS, COX activity was reduced by 29% in MH compared to NH, and by 30% in MH compared to PH (p ≤ 0.006). Results remained significant controlling for age, gender, education, and APOE. No differences were found between PH and NH. COX measures discriminated MH from the other groups with accuracy ≥75%, and relative risk ≥3 (p ≤ 0.005). Among NL with LOAD-parents, only those with MH showed reduced COX activity in platelet mitochondria compared to PH and NH. The association between maternal history of LOAD and systemic COX reductions suggests transmission via mitochondrial DNA, which is exclusively maternally inherited in humans.

Monozygotic twins with variable expression of Van der Woude Syndrome

Monozygotic twins with variable expression of Van der Woude Syndrome

Preeclampsia, a disease of the maternal endothelium: the role of antiangiogenic factors and implications for later cardiovascular disease.

Preeclampsia is a clinical syndrome defined as the new onset of hypertension and proteinuria during the second half of pregnancy.1 It afflicts 3% to 5% of pregnancies and is a leading cause of maternal mortality, especially in developing countries.2,3 Because the only known remedy is delivery of the placenta, in developed countries preeclampsia is an important cause of premature delivery, usually medically indicated for the benefit of the mother. This results in infant morbidity and substantial healthcare expenditure.4 Despite the considerable morbidity and mortality, the cause of preeclampsia has remained enigmatic. Both hypertension and proteinuria implicate the endothelium as the target of the disease. The hypertension of preeclampsia is characterized by peripheral vasoconstriction and decreased arterial compliance.5,6 The proteinuria of preeclampsia is associated with a pathognomonic renal lesion known as glomerular endotheliosis, in which the endothelial cells of the glomerulus swell and endothelial fenestrations are lost.7,8 Podocyturia has been recently associated with preeclampsia during clinical disease9; however, whether this is the cause or effect of proteinuria is unknown. The glomerular filtration rate is decreased compared with normotensive pregnant women; in rare cases, acute renal failure may develop. Preeclampsia is a systemic vascular disorder that may also affect the liver and the brain in the mothers. When the liver is involved, women may present with abdominal pain, nausea, vomiting, and elevated liver enzymes. Pathological examination of the liver reveals periportal and sinusoidal fibrin deposition and, in more extreme cases, hemorrhage and necrosis.10 The severe preeclampsia variant HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) occurs in ≈20% of women with severe preeclampsia,11 and is named not only for the liver involvement, but also for the disorder of the coagulation system that develops.12 Approximately 20% of …

GENETIC COMPONENTS TO CASTE ALLOCATION IN A MULTIPLE-QUEEN ANT SPECIES

Reproductive division of labor and the coexistence of distinct castes are hallmarks of insect societies. In social insect species with multiple queens per colony, the fitness of nestmate queens directly depends on the process of caste allocation (i.e., the relative investment in queen, sterile worker and male production). The aim of this study is to investigate the genetic components to the process of caste allocation in a multiple-queen ant species. We conducted controlled crosses in the Argentine ant Linepithema humile and established single-queen colonies to identify maternal and paternal family effects on the relative production of new queens, workers, and males. There were significant effects of parental genetic backgrounds on various aspects of caste allocation: the paternal lineage affected the proportion of queens and workers produced whereas the proportions of queens and males, and females and males were influenced by the interaction between parental lineages. In addition to revealing nonadditive genetic effects on female caste determination in a multiple-queen ant species, this study reveals strong genetic compatibility effects between parental genomes on caste allocation components.

Identification of an FBN1 mutation in bovine Marfan syndrome‐like disease

Mutations in the gene encoding fibrillin-1 (FBN1), a component of the extracellular microfibril, cause Marfan syndrome (MFS). Frequent observation of cattle with a normal withers height, but lower body weight than age-matched normal cattle, was recently reported among cattle sired by phenotypically normal Bull A, in Japanese Black cattle. These cattle also showed other characteristic features similar to the clinical phenotype of human MFS, such as a long phalanx proximalis, oval face and crystalline lens cloudiness. We first screened a paternal half-sib family comprising 36 affected and 10 normal offspring of Bull A using the BovineSNP50 BeadChip (illumina). Twenty-two microsatellite markers mapped to a significant region on BTA10 were subsequently genotyped on the family. The bovine Marfan syndrome-like disease (MFSL) was mapped onto BTA10. As FBN1 is located in the significant region, FBN1 was sequenced in Bull A, and three affected and one normal cattle. A G>A mutation at the intron64 splicing accepter site (c.8227-1G>A) was detected in 31 of 36 affected animals (84.7%). The c.8227-1G>A polymorphism was not found in 20 normal offspring of Bull A or in 93 normal cattle unrelated to Bull A. The mutation caused a 1-base shift of the intron64 splicing accepter site to the 3' direction, and a 1-base deletion in processed mRNA. This 1-base deletion creates a premature termination codon, and a 125-amino acid shorter Fibrillin-1 protein is produced from the mutant mRNA. We therefore conclude that the c.8227-1G>A mutation is causative for MFSL. Furthermore, it was suggested that Bull A exhibited germline mosaicism for the mutation, and that the frequency of the mutant sperm was 14.9%.

Australian Women’s Perceptions of Breast Cancer Risk Factors and the Risk of Developing Breast Cancer

Background Numerous studies have shown that the majority of women overestimate both their own risk and the populations’ risk of developing breast cancer. A number of factors have been found to correlate with perceived risk. Methods This paper reports on a telephone survey of a nationally representative sample of approximately 3,000 Australian women aged 30 to 69 years, conducted in 2007, and compares the findings with those of a similar survey conducted in 2003. Results There was a clear tendency for respondents to overestimate the proportion of women who will develop breast cancer during their lifetime. Approximately half the respondents perceived themselves as being at the same risk of developing breast cancer as other women their age; older respondents were more likely to perceive themselves to be at a lower than average risk. Family history was recognized as a risk factor for breast cancer, although there was evident confusion in relation to risk from paternal family history. It was also evident that the association between age and risk status is poorly understood, and misconceptions of breast cancer risk factors identified in the previous survey persisted in 2007. Conclusion Overall, these results suggest that there remains an educational challenge if we seek to increase the accuracy of women’s perceptions of their risk for developing breast cancer, primarily in relation to the significance of age and family history as breast cancer risk factors.

A Good Old Note: The Serpent in Thomas Hardy's World and Works

Abstract Hardy's works reference many musical instruments used in both church (west gallery) bands and his paternal family's leadership of the Stinsford Church gallery band: while the Hardy family band consisted entirely of string instruments (violins and cello), Hardy makes frequent reference to the clarinet (rendered as clarionet and clar'net), barrel organ, oboe (hautboy), drum, tambourine and serpent — the last of these is the subject of this article. Possibly the least known instrument found in Hardy's bands — if the most exotic — the serpent, its development and use in England in the early 19 th century, is of considerable interest to organologists and students of the west gallery musical tradition. Hardy's works that speak of the serpent shed light on a colourful corner of his writing and provide an opportunity to gain a better understanding of the instrument's role and sound in nineteenth century England.

Paternal depression: an examination of its links with father, child and family functioning in the postnatal period

Background: Maternal depression is common and is known to affect both maternal and child health. One of the mechanisms by which maternal depression exerts its effects on child health is through an increased rate of parental disharmony. Fathers also experience depression, but the impact of this on family functioning has been less studied. The aim of this study was to investigate the association between paternal depressive disorder and family and child functioning, in the first 3 months of a child's life. Methods: A controlled study comparing individual and familial outcomes in fathers with (n=54) and without diagnosed depressive disorder (n=99). Parental couple functioning and child temperament were assessed by both paternal and maternal report. Results: Depression in fathers is associated with an increased risk of disharmony in partner relationships, reported by both fathers and their partners, controlling for maternal depression. Few differences in infant's reported temperament were found in the early postnatal period. Conclusions: These findings emphasize the importance of considering the potential for men, as well as women, to experience depression in the postnatal period. Paternal symptoms hold the potential to impact upon fathers, their partners, and their children. Depression and Anxiety, 2011. © 2011 Wiley-Liss, Inc.

Breast and Ovarian Cancer: The Forgotten Paternal Contribution

Five to 10% of all cases of breast and ovarian cancer are attributed to a heritable genetic predisposition. Transmission of BRCA1 and BRCA2 mutations is equally likely through maternal or paternal lineage; however, fewer referrals to cancer genetics clinics appear to be made for a paternal, than maternal, family history of breast and/or ovarian cancer. To examine this potential bias, a retrospective review of 315 patient and family charts was conducted by one familial cancer clinic in Toronto, Canada. Referral letters, risk estimates, and family histories were analyzed to identify significant differences between patients referred with maternal and paternal family histories. It was determined that patients are approximately five times more likely to be referred with a maternal family history of breast and/or ovarian cancer as compared to those with a paternal family history (p = <.0001). Individuals with a paternal family history were found to have a different, and higher, pattern of risk estimates (p = .00064). No significant difference was seen between the type of referrals sent by general practitioners, oncologists, and gynecologists. Recommendations to increase the awareness of paternal family history in assessing cancer risk are provided.

Paternity Testing: A Non‐Linkage Based Marker‐Assisted Selection Scheme for Outbred Forage Species

ABSTRACTIn many major perennial forage species, genomic tools and infrastructure development has advanced enough that their utilization in marker‐assisted selection (MAS) can be cheaply explored. This paper presents a paternity testing MAS in diploid red clover (Trifolium pratense L.). Utilizing individual plant phenotypes, known maternity, and molecular marker‐determined paternity, paternal and maternal breeding values are calculated and selection on both parents is accomplished. Paternity testing MAS is demonstrated in three red clover breeding populations utilizing permutation‐based truncation selection for a biomass‐persistence index trait. Permutation‐based truncation selection is accomplished by ranking parents based on 80% of total progeny per permutation. Parental rankings are then used to select among the remaining 20% of total progeny and average selection gains across all permutations are estimated. Paternity was determined from 11 simple sequence repeats (SSRs) amplified in two polymerase chain reactions (PCRs). Paternity‐based selection gains alone were more than double selection gains based on maternity alone. Inexplicably, the estimated paternal halfsib family additive genetic variance was four to five times greater than the maternal halfsib family additive genetic variance. Paternity testing MAS is implementable in other diploid forage species and allopolyploid forage species with one diploid genome and corresponding genome specific molecular markers.

A new platelet alloantigen, Swia, located on glycoprotein Ia identified in a family with fetal and neonatal alloimmune thrombocytopenia

Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by transplacental passage of maternal antibodies to fetuses whose platelets (PLTs) express the corresponding human PLT antigen (HPA). We observed a fetus with FNAIT who died from a severe intracranial hemorrhage. Analysis of maternal serum in antigen capture assay with paternal PLTs showed reactivity with PLT glycoprotein (GP)IIb/IIIa (α(IIb) β(3) ) and GPIa/IIa (α(2) β(1) integrin), indicating the presence of anti-HPA-1a and an additional alloantibody against GPIa (termed anti-Swi(a) ). By immunochemical studies, the localization of the Swi(a) antigen on GPIa/IIa could be confirmed. Analysis of paternal GPIa full-length cDNA showed a single-nucleotide substitution C(3347) T in Exon 28 resulting in a Thr(1087) Met amino acid substitution. Testing of family members by polymerase chain reaction-restriction fragment length polymorphism using MslI endonuclease showed perfect correlation with phenotyping. Extended family and population studies showed that 4 of 10 members of the paternal family but none of 500 unrelated blood donors were Swi(a) carriers. Expression studies on allele-specific transfected Chinese hamster ovary (CHO) cells confirmed that the single-amino-acid substitution Thr(1087) Met was responsible for the formation of the Swi(a) epitope. Adhesion of CHO cells expressing the Swi(a) alloantigen to immobilized collagens was not impaired compared to the wild-type control and was not inhibited by anti-Swi(a) alloantibodies. In this study we defined a new PLT alloantigen Swi(a) that was involved in a case of additional immunization against HPA-1a. Our observations demonstrate that combinations of PLT-specific alloantibodies may comprise low-frequency alloantigens.

Structural brain changes in normal individuals with a maternal history of Alzheimer's

Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor for developing the disease among cognitively normal (NL) individuals. This magnetic resonance imaging (MRI) study examines whether NL with a LOAD-affected parent show preclinical brain atrophy, and whether there are parent-of-origin effects. Voxel-based morphometry (VBM) on Statistical parametric mapping (SPM8) was used to examine volumetric T1-MRI scans of 60 late-middle-aged NL subjects, divided into 3 size-matched, demographically balanced groups of 20 subjects each, including NL with a maternal (FHm), paternal (FHp), or negative family history (FH-) of LOAD. There were no group differences for clinical and neuropsychological measures, and ApoE status. On VBM, FHm showed reduced gray matter volumes (GMV) in frontal, parietal, and temporal cortices and precuneus as compared with FH-, and in precuneus compared with FHp (p < 0.05, family-wise error [FWE]-corrected). Results remained significant controlling for age, gender, education, ApoE, and total intracranial volume. No differences were observed between FHp and FH- in any regions. NL FHm showed reduced GMV in LOAD-affected brain regions compared with FH- and FHp, indicating higher risk for Alzheimer's disease. Our findings support the use of regional brain atrophy as a preclinical biomarker for LOAD among at-risk individuals.

Parental family stress during pregnancy and cognitive functioning in early childhood: The Generation R Study

We investigated whether parental family stress during pregnancy is associated with cognitive functioning in early childhood in a population-based cohort (n = 3139). Family stress was assessed using the Family Assessment Device at the 20th week of pregnancy and was reported by mothers and fathers. Mothers completed the MacArthur Communicative Development Inventory, measuring children's verbal cognitive functioning, when children were 18 months and they completed the Parent Report of Children's Abilities, measuring nonverbal cognitive functioning, when children were 2 years old. Maternal prenatal family stress was related to children's low word comprehension and poorer nonverbal cognitive development independent of paternal reports. In a subset of 639 children, maternal prenatal family stress was also associated with observational assessments of poor effortful control at age 37 months. Paternal prenatal family stress was only related to poorer nonverbal cognitive development, independent of the mother. When both parents had high levels of prenatal family stress, children displayed particularly poor nonverbal cognitive development. These findings emphasize the significance of parental prenatal family stress for child developmental outcomes.

“Footprints in the Bathroom”: The Role of Spirituality in Patient Diagnosis

CASE Lucy is a 12-year-old Latina whose mother brought her to the pediatric clinic for help with her anxiety symptoms, hearing voices, and episodes of spacing out. Lucy did not cry at birth secondary to vocal cord paralysis and still has the tracheostomy performed at a few days of life. In addition to her neonatal intensive care unit stay, she has been hospitalized for pneumonia. Her mother says she is sickly and has a weak immune system due to her asthma symptoms. Lucy also experiences somatic complaints related to gastroesophageal reflux and constipation.Lucy is described as being another world and must be called several times before she responds. Lucy states she is nervous all the time and often experiences a fast heartbeat, chest pain, and headache. Her attention and internalizing problems began at age 4 years and have worsened since she entered adolescence. When she is alone in the dark, she sees an unknown person and becomes frightened. She hears the voice of her paternal uncle telling her something will harm her mother and runs crying to check on her. Lucy also says she hears voices of paternal family members fighting. She has dreamed that her paternal uncle stabbed her in an alley. Lucy reports experiencing sadness and feelings of wanting to die. She has not tried to harm herself and has no plan to do this. She states that she does not know when she is awake or asleep and hate people talking in my head. She does not report drug use.Lucy's family is bilingual, English and Spanish. Her mother works part-time as a nutritionist, and her father is a machinist. Her father receives counseling for anger management, and there have been previous unsub- stantiated child abuse reports involving Lucy and her younger brother. The maternal uncle has been involved in a gang and attempts to phone Lucy's mother, who does not wish to have contact with him. Lucy's mother expresses strong Christian religious and spiritual beliefs, including demons and spirits that may enter her home and can be cast off with prayer. Recently, the family purchased a cuadro (picture) at a yard sale, and Lucy's mother said this resulted in footprints in the bathroom that are disappearing with prayer, guidance from the church minister, and discarding of the cuadro.The primary pediatrician ordered a home school program, given Lucy's frequent illnesses. She is progressing well with a special education teacher. Her recent psychological evaluation at school showed a below average nonverbal intelligence quotient, with strengths in the areas of perceptual, logical, and abstract relationships. Lucy's mother in the past has been hesitant to follow through with psychiatric evaluation because it is up to God.In the clinic, she is pale and slender with an ethereal look. She is awake and alert with appropriate affect and mentation. Her tracheostomy is intact without any respiratory distress noted. There are no signs of drug use or active hallucinations. You are left wondering whether these voices need psychiatric management.

Race &amp; Inheritance in Barack Obama's Dreams from My Father

When and how did Barack Obama's now well-known “hope” mantra take shape? Carpio's essay explores this question through close readings of key passages from Obama's autobiography. It is nearly three hundred pages into the autobiography before the phrase “the audacity of hope” appears, at the end of the “Chicago” section. Obama has just been accepted to Harvard Law School and has yet to take his first trip to Africa to find his paternal family when he hears the phrase from his infamous ex-pastor, Jeremiah Wright. The essay places this moment from the “Chicago” section in the context of the entire autobiography to illuminate why, for Obama, it takes audacity to hope that we can transcend America's history of racial conflict. In the process, the essay reveals Obama's dark view of race relations in America before he became the symbol of a supposedly post-racial America that he is now.

Coronal Synostosis Syndrome (Muenke Syndrome)

Muenke syndrome is a fibroblast growth factor receptor 3 (FGFR-3)-associated coronal craniosynostosis syndrome, which was first described in 1997. We report an infant girl who was born to a 29-year-old primapara at 38 weeks' gestation. When evaluated at 3 days old, physical examination revealed a high forehead with frontal bossing, upturned nose, arched palate, shallow midface structures, and heavily ridged coronal sutures bilaterally. Clinically, the infant seemed to be neurologically normal. Skull radiographs and computed tomography confirmed the presence of bilateral coronal synostosis, with patency of all other sutures. Family history was remarkable, in that the infant's father, paternal grandmother, and a paternal cousin demonstrated subtle craniofacial features, which had not been previously identified. Mutation analysis of FGFR-3 revealed a missense mutation in exon 6, c.749 C>G, with a resultant amino acid change from proline to arginine at codon 250 (P250R), in keeping with Muenke syndrome (Am J Hum Genet 1997;60:555-564). The mutation was subsequently identified in her father, suggesting variable expression in this family, as he had only mild midfacial flattening. At 9 months of age, our patient underwent anterior cranial expansion, correction of orbital hypertelorism, intracranial orbital osteotomies, and advancement of the frontal bandeau. She tolerated the procedure well and has done well postoperatively. We report the case of an infant with Muenke syndrome, with evidence of variable expressivity within the paternal family. The pertinent literature, in which only 2 prior Canadian cases were identified, is reviewed.

Components of family history associated with women's disease perceptions for cancer: A report from the Family Healthware™ Impact Trial

PurposeTo determine the specific components of family history and personal characteristics related to disease perceptions about breast, colon, and ovarian cancers. MethodsBaseline, cross-sectional data on 2,505 healthy women aged 35–65 years enrolled from 41 primary care practices in the cluster-randomized Family Healthware™ Impact Trial, assessed for detailed family history and perceived risk, perceived severity, worry, and perceived control over getting six common diseases including breast, colon, and ovarian cancers. ResultsParticipants provided family history information on 41,841 total relatives. We found evidence of underreporting of paternal family history and lower perceived breast cancer risk with cancer in the paternal versus maternal lineage. We observed cancer-specific perceived risks and worry for individual family history elements and also found novel “spillover” effects where a family history of one cancer was associated with altered disease perceptions of another. Having a mother with early-onset breast or ovarian cancer was strongly associated with perceived risk of breast cancer. Age, parenthood, and affected lineage were associated with disease perceptions and ran counter to empiric risks. ConclusionsUnderstanding patients' formulation of risk for multiple diseases is important for public health initiatives that seek to inform risk appraisal, influence disease perceptions, or match preventive interventions to existing risk perceptions.

Hiding in Plain Sight: A Case of Tarlov Perineural Cysts

A 52-year-old woman sought help for intractable lumbosacral pain, which began after she lifted a heavy object and fell onto her back more than 2 decades ago. Additional symptoms included burning, numbness, tingling, and pain in her right hip, posterior thigh, leg, and toes, and diminished sensation and sensitivity throughout her right leg and foot. Muscle spasms/ cramps, which often interrupted sleep, were intermittently present in her right buttock and right lower extremity. Right-foot drop impaired her ability to walk, and she used a wheeled walker with a seat because she could not walk more than a few steps without sitting. Other problems included: Severe pressure-type headaches, chronic abdominal and pelvic pain, cervical and thoracic back pain, frequent urinary tract infections, and urinary incontinence. Her pain increased with sitting, standing, and walking, and had been refractory to ibuprofen 800 mg tid, gabapentin 300 mg tid, oxycodone/acetaminophen 5/325 mg q4h PRN, and cyclobenzaprine 10 mg tid. Her medical history was unremarkable and her family history was notable for above-average height; most women in her paternal family are 5’10’’ to 6’ tall, and most men are 6’4’’ and taller. Many died in their 40s, and her brother and sister had been diagnosed with possible multiple sclerosis. Magnetic resonance imaging (MRI) of her pelvis revealed sacral nerve root cysts that were more completely imaged by sacral MRI (Fig 2). An MRI of the cervical spine from 2007 showed only mild C4-5 disc protrusion, but a repeat MRI in 2009 noted multilevel mild degenerative changes and small (#.6 cm) perineurial cysts at C4-5, C5-6, C6-7, C7-T1. In 2007, an MRI of the thoracic spine was interpreted as normal. The patient stated, ‘‘Everything in my life has been destroyed by these symptoms. It took over 2 decades

P.1.e.028 Increase of whole brain volume and gray and white matter tissue in OCD: a volumetric and voxel-based morphometry MRI study

Having a parent affected with late-onset Alzheimer's disease (LOAD) is a major risk factor for developing the disease among cognitively normal (NL) individuals. This magnetic resonance imaging (MRI) study examines whether NL with a LOAD-affected parent show preclinical brain atrophy, and whether there are parent-of-origin effects. Voxel-based morphometry (VBM) on Statistical parametric mapping (SPM8) was used to examine volumetric T1-MRI scans of 60 late-middle-aged NL subjects, divided into 3 size-matched, demographically balanced groups of 20 subjects each, including NL with a maternal (FHm), paternal (FHp), or negative family history (FH−) of LOAD. There were no group differences for clinical and neuropsychological measures, and ApoE status. On VBM, FHm showed reduced gray matter volumes (GMV) in frontal, parietal, and temporal cortices and precuneus as compared with FH−, and in precuneus compared with FHp (p < 0.05, family-wise error [FWE]-corrected). Results remained significant controlling for age, gender, education, ApoE, and total intracranial volume. No differences were observed between FHp and FH− in any regions. NL FHm showed reduced GMV in LOAD-affected brain regions compared with FH− and FHp, indicating higher risk for Alzheimer's disease. Our findings support the use of regional brain atrophy as a preclinical biomarker for LOAD among at-risk individuals.

Maternal Family History of Diabetes Is Associated With a Reduced Risk of Cardiovascular Disease in Women With Type 2 Diabetes

OBJECTIVETo investigate whether parental family history of diabetes influences cardiovascular outcomes in type 2 diabetes.RESEARCH DESIGN AND METHODSWe studied 1,294 type 2 diabetic patients (mean age 64.1 years, 51.2% female) recruited to a community-based cohort study from 1993 to 1996 and followed until mid-2006. A data linkage system assessed all-cause and cardiac mortality, incident myocardial infarction, and stroke. Cox proportional hazards modeling was used to determine the influence of maternal or paternal family history on these outcomes.RESULTSA maternal family history of diabetes was reported by 20.4% of the cohort, 8.3% reported paternal family history, and 2.0% reported both parents affected. Maternal and paternal family history was associated with earlier age of diabetes onset, and maternal family history was associated with worse glycemic control. For all patients, maternal family history was significantly associated with reduced risk of all-cause mortality and cardiac mortality. When analyzed by sex, maternal family history had no effect on male patients, whereas female patients with diabetic mothers had significantly reduced hazard ratios for death from all causes (0.63 [95% CI 0.41–0.96]; P = 0.033), for death from cardiac causes (0.32 [0.14–0.72]; P = 0.006), and for first myocardial infarction (0.45 [0.26–0.76]; P = 0.003). Paternal family history status was not associated with these outcomes.CONCLUSIONSA maternal family history of diabetes confers relative protection against cardiovascular disease in female patients but not in male patients with type 2 diabetes. Paternal family history is associated with risks equivalent to those without a family history of diabetes. Some of the clinical heterogeneity of type 2 diabetes is related to maternal transmission effects with differential impact on male and female patients.