Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden

Westerlind, Helga; Ramanujam, Ryan; Uvehag, Daniel; Kuja‐Halkola, Ralf; Boman, Magnus; Bottai, Matteo; Lichtenstein, Paul; Hillert, Jan

doi:10.1093/brain/awt356

Cited by 141 publications

(111 citation statements)

References 39 publications

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“…These small effect sizes may be related to P(resistance i ) being high in adulthood either because existing members of the microbiota prevent new strains from establishing themselves or because the partner has already developed immune mechanisms to eliminate the strains(s). Although increased relative risk upon cohabitation with an affected spouse may be small, the relative risk of Crohn's disease (51), rheumatoid arthritis (49), or multiple sclerosis (52) is highly increased when a sibling is affected (6.3, 4.6, and 7.1, respectively). In the context of microbial inheritance, the shared risk factors are stably colonized microbial strains inherited between family members that increase (or decrease) the probability of complex disease over a lifetime.…”

Section: A Model Of Microbial Inheritancementioning

confidence: 99%

Identifying strains that contribute to complex diseases through the study of microbial inheritance

Faith¹,

Colombel

Gordon

2015

Proc. Natl. Acad. Sci. U.S.A.

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It has been 35 y since Carl Woese reported in PNAS how sequencing ribosomal RNA genes could be used to distinguish the three domains of life on Earth. During the past decade, 16S rDNA sequencing has enabled the now frequent enumeration of bacterial communities that populate the bodies of humans representing different ages, cultural traditions, and health states. A challenge going forward is to quantify the contributions of community members to wellness, disease risk, and disease pathogenesis. Here, we explore a theoretical framework for studies of the inheritance of bacterial strains and discuss the advantages and disadvantages of various study designs for assessing the contribution of strains to complex diseases.microbial inheritance | strain-resolution human microbial ecology analyses | effector strains | health | disease

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Section: A Model Of Microbial Inheritancementioning

confidence: 99%

Identifying strains that contribute to complex diseases through the study of microbial inheritance

Faith¹,

Colombel

Gordon

2015

Proc. Natl. Acad. Sci. U.S.A.

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“…1 Although the exact proportion of MS risks that can be explained by these factors is difficult to determine, estimates based on genetic and epidemiological studies over the last few decades suggest that up to 60-70% of the total risk of MS could be attributed to genetic factors. 2,3 However, the susceptibility loci identified to date by genome-wide association studies can account for only a part of this genetic risk, and further studies using sophisticated techniques are necessary to identify the missing heritability of the MS risk. 4 At the same time, there is growing interest in the epigenetics of complex diseases including MS. Epigenetics refers to the study of mechanisms that regulate gene expression without altering the DNA sequence, 5,6 and these are known to play important roles in various physiological and pathological conditions including normal development, cell differentiation, cancer, developmental disorders, and psychiatric diseases.…”

Section: Introductionmentioning

confidence: 99%

Epigenetics in multiple sclerosis

Miyazaki

Niino

2015

Clinical & Exp Neuroim

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The development of multiple sclerosis (MS) is based on complex interactions between genetic and environmental factors. Epigenetic regulation is a biological phenomenon defined as the modification of gene expression without alteration of the DNA sequence, and is currently thought to underlie the interactions between the genetic and environmental risks of MS. The molecular mechanisms of epigenetics include DNA methylation, histone modification, and microRNAs. Observational data obtained from epidemiological studies of MS, such as the parent-of-origin effect and the longitudinal increase in female patients, suggest that epigenetic mechanisms are involved in MS development, although the molecular basis remains unclear. Interestingly, environmental factors related to the development of MS, such as Epstein-Barr virus, smoking, and vitamin D, have been shown to regulate gene expression through epigenetic mechanisms in some experimental settings. One study showed no reproducible differences among DNA methylation profiles in peripheral blood CD4 + T cells between three monozygotic twin pairs discordant for MS. However, several studies have shown that dysregulated DNA methylation of genes is related to abnormal immune reactions and post-translational modifications of myelin proteins in MS brain samples. In addition, abnormal microRNA profiles have been reported in brain tissues and peripheral blood immune cells obtained from MS patients. In this article, we will review the studies on the epigenetics of MS and discuss the perspectives for future research.

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“…For dizygotic twins, the risk for the second twin developing MS is about 4%, and for monozygotic twins the risk is about 30% over their lifetime. 7,8 In terms of environmental risks, there was previous concern over use of oral contraceptives, which has been dispelled by studies showing both no effect and even possible association with a milder MS course. It is also important that women with MS and their offspring are not dissuaded from using oral contraceptives over concerns of developing MS. 9,10 Furthermore, familiarity with pregnancy risks with MS disease-modifying therapies (DMTs) can lead to safe family planning practices.…”

mentioning

confidence: 99%

Exploring Patients’ Knowledge and Misconceptions about Multiple Sclerosis and Pregnancy

Wesley¹,

Fabian²,

Krieger³

2016

US Neurology

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Multiple sclerosis (MS) is a lifelong neurologic disease affecting the central nervous system and resulting in demyelination and axonal loss over time. Symptoms are widely variable and often involve motor and sensory impairment, vision loss, gait disturbance, cognitive dysfunction, and fatigue. Furthermore, MS is a disease common to women of childbearing age, with 70% of patients being women and with 90% of patients presenting between the ages of 15 and 50.1 Family planning must be taken into account at time of diagnosis and when discussing which disease modifying agent to employ. Accurate knowledge and understanding of family planning issues is important for best outcomes.The relationship between pregnancy and relapse outcomes is complex and Education about peripartum concerns is also paramount. In a study of 461 women with MS, there was a higher rate of caesarian section; however, these findings represented a concurrently higher rate of planned, rather than emergency, caesarian sections, 5 a finding that might reflect an overly cautious approach. Previous practice advocated for caesarian sections to avoid pelvic floor trauma and thus exacerbation of preexisting urinary frequency and bladder control issues; however, it was shown in a study of 273 women in 2006 that urinary incontinence postpartum was more related to duration and severity of MS and not method of delivery. AbstractMultiple sclerosis (MS) has a high incidence in women of childbearing age. Accurate understanding of family planning matters is crucial for best outcomes. Methods: Thirty-seven women with MS aged 18 to 50 completed an anonymous questionnaire at an MS Center in New York City. There were 22 questions pertaining to four main categories: effect of pregnancy on MS, effect of MS on pregnancy, MS medication safety during pregnancy and breastfeeding, and effect of MS on offspring. Results: Mean age of patients was 36 years (standard deviation [SD] ±5.6); 86% had relapsing-remitting (RRMS). Mean time since diagnosis was 6.7 years (SD±5.2); 30.6% had been pregnant since diagnosis. Average correct score was 32.8% (SD±20.3), and while higher in patients who had been pregnant since diagnosis, 40.5% (SD±24.7) versus 31.3% (SD±17.9), there was no statistically significant difference; p=0.21. Largest knowledge deficit pertained to effect of MS on reproduction: average score 27.7% (SD±10.1). Only 21.0% knew that relapses can be treated with steroids during pregnancy; 50.0% of those with prior pregnancy knew this fact. Thirtyfour percent of patients on disease-modifying therapies (DMTs) reported not consistently using birth control. Conclusions: Our data identified misconceptions on important reproductive topics. It is important that providers educate effectively their patients on matters of reproduction.

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Modest familial risks for multiple sclerosis: a registry-based study of the population of Sweden

Cited by 141 publications

References 39 publications

Identifying strains that contribute to complex diseases through the study of microbial inheritance

Identifying strains that contribute to complex diseases through the study of microbial inheritance

Epigenetics in multiple sclerosis

Exploring Patients’ Knowledge and Misconceptions about Multiple Sclerosis and Pregnancy

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