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Hallux valgus - an autosomal dominant trait?

Discussion in 'Gerontology' started by Hylton Menz, May 14, 2007.

  1. Hylton Menz

    Hylton Menz Guest

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    From the Journal of Foot and Ankle Surgery :

    Pique-Vidal C, Sole MT, Antich J. Hallux valgus inheritance: pedigree research in 350 patients with bunion deformity. J Foot Ankle Surg 2007 May-Jun;46(3):149-54

    Our objective was to construct 3-generation pedigree charts from 350 patients with hallux valgus. During a 1-year period, all consecutive patients (n = 1174) with a painful bunion deformity evaluated roentgenographically were asked to complete a detailed 3-generation family history questionnaire. We studied 350 probands (22 men, 328 women; male/female ratio, 1:14.9; mean age, 47.8 years). Juvenile hallux valgus was diagnosed in 15 patients. Three or more affected members were observed in pedigrees from 244 probands, 2 affected members in 71, and 1 affected member in 35 (proband) (affected subjects per pedigree ranged from 1 to 16). Ninety percent of probands had at least 1 family member affected. The hallux valgus penetrance according to pedigrees from all probands was 56%. The female sex predominated with regard to the gender of parents with hallux valgus, affected branch of the family, and gender of relatives with bunion deformity. Severity of hallux valgus was not significantly influenced by gender, the affected branch of the family, or gender of the affected relatives. Family history of bunion deformity was present in 90% of probands, with vertical transmission affecting some family members across 3 generations, which is compatible with autosomal dominant inheritance with incomplete penetrance.​
  2. Admin2

    Admin2 Administrator Staff Member

  3. :pigs:

    The incomplete penetrance is key here. What the authors are saying is that the inheritance looks a bit like autosomal dominant but it doesn't fit the model. Wot no segregation analysis?
    From Spooner S.K.: Predictors of hallux valgus: A study of heritability. PhD Thesis. University of Leicester 1997
    "The theory of genetic inheritance as an aetiological factor in hallux valgus has been proposed from the patterns of aggregation of the deformity in families, from the preponderance of affected females, and from the prevalence of the condition in barefooted communities. However, little empirical evidence has supported the existance of such a relationship.

    To the authors knowledge, only one [Now two!] study supports the hypothesis that hallux valgus is due to the expression of a single mendelian gene. Johnston (1956) proposed that the pattern of inheritance of hallux valgus was autosomal dominant with incomplete penetrance, following his study of one seven generation family (101 subjects), exhibiting hallux valgus and pes planus. Hallux valgus was present in every generation of the family. Except in two cases, all of the offspring of the affected parents exhibited hallux valgus. The children of the two unaffected offspring were also affected."

    Much cut

    "From the evidence presented, it appears likely that genetic determination has a role in the aetiology of hallux valgus. It is unknown whether the condition is directly inherited or is a secondary result of another genetically influenced factor. Although hallux valgus could be the result of the expression of a single gene (Johnston 1956), it appears unlikely that this is the case. Indeed very few single gene human traits have been identified. Deviation of the hallux on its metatarsal is present within the population in varying degrees; the clear cut distinction of deviated or not that one should normally attribute to the segregation of a single gene is not observed. Moreover, since environment is believed to be significant in the development of the deformity, the proposed pattern of inheritance must be considered multifactorial. Multifactorial traits are those that involve two or more genes and are strongly influenced by the environment."

    I then went on to demonstrate that hallux valgus was indeed characteristic of a multifactorial trait through heritability analyses and predictive model building in a study group of 579 individuals.
    Last edited: Oct 3, 2007
  4. Hylton Menz

    Hylton Menz Guest


    Has this data been published?


  5. No. By the time I'd finished I was sick of the sight of it and half insane.Took up my first full time teaching post and never got around to it. It's there in the British Library for all to read in full.
  6. Stanley

    Stanley Well-Known Member

    Simon, I agree that there is a genetic determination.

    During my fellowship, I spent some time with Morton Kurzweil DPM, the inventor of the OED. (The lucite rectangle with the clear protractor attached to it)
    I went to his office in the seedier side of town, and I said "Morty what are you going to teach me today?":morning:
    He thought about it and said "HAV is hereditary, and it comes from the mother's side of the family".
    I asked "How do you know?", and he said "a woman brought her 10 children in, and they all had HAV".
    I asked "How do you know that the HAV came from the mother's side?":confused:
    He replied, "They all had different last names". :eek:
    After being a member of this listserve, I realize that I missed something.:bang: I now know I that I should have asked him if any fathers had brought in 10 different children from 10 different mothers. :D

  7. This tale from Stanley has great merit. In studying genetic traits often the aim is to differentiate "nature" from "nurture". Hence in quantitative genetics the ideal is to find groups of identical twins who have been seperated at birth- they share 100% genotype, with minimum shared environment- only the womb. Shared environment elevates the heritability= pain in the ass. These groups of people exist and are mostly signed up to every trial that is going. Unfortunately from our perspective, the foot and it's disorders is pretty low in the pecking order. I tried to access some of those on the "twin register" when I was doing this kind of work- as I recall a Dr Tim Spector was "in control" then, he was looking into RA- needless to say I couldn't get near his subjects! You can also do the opposite i.e. look at adopted siblings, who share environment but not genotype.

    Identical (MZ) twin studies are potentially very powerful in unwinding the nature of foot pathology and care (not just those seperated at birth). There is / used to be? the Minnesotta twin convention which is a feast for genetic researchers. I always fancied going there and collecting some footy data. If anyone likes the idea/ lives locally: I have experience in working with this kind of data, and maybe enough years have passed now that I'd be willing to look again at this type of research. Could be good mileage in orthoses research using Mz twins- as close as you are likely to get to matched pairs- they be clones! But anything is possible. From what I know of the convention though, you need to capture as much data as you can, as quick as possible.

    Please though, for the sake of medical science, remember: if you give birth to Mz twins- seperate them!
  8. Stanley

    Stanley Well-Known Member

    Don't know about the Minnesota twin convention, but in Ohio there is a huge twins day (in of course Twinsburg).



  9. THanks Stanley. This is probably what I was thinking of.
  10. drsarbes

    drsarbes Well-Known Member

    Hi Simon:

    I know this is an old thread, I just found it.

    "I then went on to demonstrate that hallux valgus was indeed characteristic of a multifactorial trait through heritability analyses and predictive model building in a study group of 579 individuals."

    Did you ever do anything with this data?
    You stated that there are very few traits attributed to a single dominant gene....really?

    This initial study that was presented in this thread. Did you see any problems with it?

  11. I wrote it up as a PhD thesis, which incidentally should be dated 1998 not 1997 as I wrote above, I obviously had my viva copy in front of me when I was referring to it which reads 1997- sorry for any confusion. As I said at the start of the thread, when Hylton asked me if this data had been published, for a number of reasons (not least that I was absolutely sick of the sight of it) I never got around to condensing it into a paper.

    Relatively speaking. Many human traits are polygenic and/or multifactorial see here:http://books.google.com/books?id=X9...rIy-BA&sa=X&oi=book_result&ct=result&resnum=7. Also of note is that I was quoting my thesis which was written over a decade ago- I suspect many more have been discovered since I wrote that.

    Out of interest here's a link to the catalogue of everything genetic! This includes dominant, recessive, x, y, and uncle Tom Cobley and all. I've linked you to the stat's page: http://www.ncbi.nlm.nih.gov/Omim/mimstats.html

    As I said, "incomplete penetrance" is really just a "fudge" because the pedigrees look a bit like autosomal dominant, but not quite. Also, major gender bias in proband selection. Also major gender bias in those affected by hallux valgus here. I have not read the full paper, but it appears that they only actually examined the probands and that the questionnaire was used to determine the presence of hallux valgus in other family members. Did your paternal grandparents have hallux valgus? (I have no idea) What about your maternal grandparents?(ditto) I know my mum does, my sister does, but me and my brother don't. Does my four year old daughter have hallux valgus? No. Does this mean she is not going to get it? These are a few issues that spring to mind. I'd need to read the whole paper to really make comment.
    Last edited: May 19, 2009
  12. NewsBot

    NewsBot The Admin that posts the news.

    Genetic Influences on Hallux Valgus in Koreans: The Healthy Twin Study.
    Lee CH, Lee S, Kang H, Jung DE, Song YM, Lee K, Lee K, Hwang J, Sung J.
    Twin Res Hum Genet. 2014 Mar 11:1-6.
  13. NewsBot

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    Genome-wide association meta-analyses to identify common genetic variants associated with hallux valgus in Caucasian and African Americans
    Yi-Hsiang Hsu, Youfang Liu, Marian T Hannan, William Maixner, Shad B Smith, Luda Diatchenko, Yvonne M Golightly, Hylton B Menz, Virginia B Kraus, Michael Doherty, AG Wilson, Joanne M Jordan
    J Med Genet doi:10.1136/jmedgenet-2015-103142
  14. drhunt1

    drhunt1 Well-Known Member

    As it is with growing pains in children, and RLS in adults: it is not the bunion that is inherited, but the foot type that leads to it, that is. Hope this helps.
  15. NewsBot

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    Hallux valgus, by nature or nurture? A twin study.
    Munteanu SE, Menz HB, Wark JD, Christie JJ, Scurrah KJ, Bui M, Erbas B, Hopper JL, Wluka AE
    Arthritis Care Res (Hoboken). 2016 Nov 18. doi: 10.1002/acr.23154.
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    Association of Vitamin D Receptor Gene TaqI, BsmI, FokI, and ApaI Polymorphisms and Susceptibility to Hallux Valgus in the Chinese Population
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    JFAS; Article in Press
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    Relationship Between Genetic Polymorphisms of TNF Gene and Hallux Valgus Susceptibility.
    Yang J et al
    Genet Test Mol Biomarkers. 2019 May 7
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    Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians
    Liubov Arbeeva, Michelle Yau, Braxton D. Mitchell, Rebecca D. Jackson, Kathleen Ryan, Yvonne M. Golightly, Marian T. Hannan, Amanda Nelson, Joanne M. Jordan & Marc C. Hochberg
    Journal of Foot and Ankle Research volume 13, Article number: 11 (2020)
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    Correlation analysis between vitamin D receptor gene polymorphism (BsmI) and hallux valgus
    X M Chen et al
    J Biol Regul Homeost Agents. 2020 Aug 28;34(4)
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    Effect of lentivirus-mediated miR-182 targeting FGF9 on hallux valgus.
    Zhang WL, Zhao DY, Zhao W, Cui Y, Li Q, Zhang ZY.
    Int J Med Sci 2021; 18(4):902-910. doi:10.7150/ijms.50984.
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    New insights into hallux valgus by whole exome sequencing study
    Jun Jia, Junyi Li, Huiqi Qu, ...
    Experimental Biology and Medicine April 29, 2021
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    Identification of copy number variants contributing to hallux valgus
    Wentao Zhou et al
    Front Genet. 2023 Mar 23
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