Editing Handedness (section)

=== Genetic factors ===
Handedness displays a complex inheritance pattern. For example, if both parents of a child are left-handed, there is a 26% chance of their child being left-handed.<ref name="McManusChris">{{cite book | last = McManus | first = Chris | name-list-style = vanc | title=Right Hand, Left Hand | publisher=Phoenix Paperbacks | year=2003 | isbn=978-0753813553}}</ref> A large study of twins from 25,732 families by Medland et al. (2006) indicates that the [[heritability]] of handedness is roughly 24%.<ref>{{cite journal | vauthors = Medland SE, Duffy DL, Wright MJ, Geffen GM, Hay DA, Levy F, van-Beijsterveldt CE, Willemsen G, Townsend GC, White V, Hewitt AW, Mackey DA, Bailey JM, Slutske WS, Nyholt DR, Treloar SA, Martin NG, Boomsma DI | display-authors = 6 | title = Genetic influences on handedness: data from 25,732 Australian and Dutch twin families | journal = Neuropsychologia | volume = 47 | issue = 2 | pages = 330–7 | date = January 2009 | pmid = 18824185 | pmc = 2755095 | doi = 10.1016/j.neuropsychologia.2008.09.005 }}</ref>

Two theoretical single-gene models have been proposed to explain the patterns of inheritance of handedness, by Marian Annett<ref>{{Cite book |first=M. |last=Annett |s2cid=53411957 |title=Language lateralization and psychosis |chapter=The genetic basis of lateralization |year=2009 |pages=73–86 |doi=10.1017/CBO9780511576744.006 |editor1-last=Sommer |editor1-first=Iris E. C. |editor2-last=Kahn |editor2-first=René S. | name-list-style = vanc |isbn=9780511576744 |hdl=2381/4737 |url=https://figshare.com/articles/chapter/The_Genetic_Basis_of_Lateralization/10088477 }}</ref> of the [[University of Leicester]], and by Chris McManus<ref name="McManusChris" /> of [[University College London|UCL]].

However, growing evidence from [[genetic linkage|linkage]] and [[genome-wide association study|genome-wide association]] studies suggests that genetic variance in handedness cannot be explained by a single genetic [[Locus (genetics)|locus]].<ref>{{cite journal | vauthors = Francks C, DeLisi LE, Fisher SE, Laval SH, Rue JE, Stein JF, Monaco AP | title = Confirmatory evidence for linkage of relative hand skill to 2p12-q11 | journal = American Journal of Human Genetics | volume = 72 | issue = 2 | pages = 499–502 | date = February 2003 | pmid = 12596796 | pmc = 379245 | doi = 10.1086/367548 }}</ref><ref>{{cite journal | vauthors = Francks C, Maegawa S, Laurén J, Abrahams BS, Velayos-Baeza A, Medland SE, Colella S, Groszer M, McAuley EZ, Caffrey TM, Timmusk T, Pruunsild P, Koppel I, Lind PA, Matsumoto-Itaba N, Nicod J, Xiong L, Joober R, Enard W, Krinsky B, Nanba E, Richardson AJ, Riley BP, Martin NG, Strittmatter SM, Möller HJ, Rujescu D, St Clair D, Muglia P, Roos JL, Fisher SE, Wade-Martins R, Rouleau GA, Stein JF, Karayiorgou M, Geschwind DH, Ragoussis J, Kendler KS, Airaksinen MS, Oshimura M, DeLisi LE, Monaco AP | display-authors = 6 | title = LRRTM1 on chromosome 2p12 is a maternally suppressed gene that is associated paternally with handedness and schizophrenia | journal = Molecular Psychiatry | volume = 12 | issue = 12 | pages = 1129–39, 1057 | date = December 2007 | pmid = 17667961 | pmc = 2990633 | doi = 10.1038/sj.mp.4002053 }}</ref><ref>{{cite journal | vauthors = Van Agtmael T, Forrest SM, Williamson R | title = Parametric and non-parametric linkage analysis of several candidate regions for genes for human handedness | journal = European Journal of Human Genetics | volume = 10 | issue = 10 | pages = 623–30 | date = October 2002 | pmid = 12357333 | doi = 10.1038/sj.ejhg.5200851 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Warren DM, Stern M, Duggirala R, Dyer TD, Almasy L | s2cid = 11711104 | title = Heritability and linkage analysis of hand, foot, and eye preference in Mexican Americans | journal = Laterality | volume = 11 | issue = 6 | pages = 508–24 | date = November 2006 | pmid = 16966240 | doi = 10.1080/13576500600761056 }}</ref><ref>{{cite journal | vauthors = Laval SH, Dann JC, Butler RJ, Loftus J, Rue J, Leask SJ, Bass N, Comazzi M, Vita A, Nanko S, Shaw S, Peterson P, Shields G, Smith AB, Stewart J, DeLisi LE, Crow TJ | display-authors = 6 | title = Evidence for linkage to psychosis and cerebral asymmetry (relative hand skill) on the X chromosome | journal = American Journal of Medical Genetics | volume = 81 | issue = 5 | pages = 420–7 | date = September 1998 | pmid = 9754628 | doi = 10.1002/(SICI)1096-8628(19980907)81:5<420::AID-AJMG11>3.0.CO;2-E }}</ref><ref>{{cite journal | vauthors = Armour JA, Davison A, McManus IC | title = Genome-wide association study of handedness excludes simple genetic models | journal = Heredity | volume = 112 | issue = 3 | pages = 221–5 | date = March 2014 | pmid = 24065183 | pmc = 3931166 | doi = 10.1038/hdy.2013.93 }}</ref><ref>{{cite journal | vauthors = Scerri TS, Brandler WM, Paracchini S, Morris AP, Ring SM, Richardson AJ, Talcott JB, Stein J, Monaco AP | display-authors = 6 | title = PCSK6 is associated with handedness in individuals with dyslexia | journal = Human Molecular Genetics | volume = 20 | issue = 3 | pages = 608–14 | date = February 2011 | pmid = 21051773 | pmc = 3016905 | doi = 10.1093/hmg/ddq475 | author-link3 = Silvia Paracchini }}</ref>{{excessive citations inline|date=March 2023}} From these studies, McManus et al. now conclude that handedness is [[polygenic]] and estimate that at least 40 [[Locus (genetics)|loci]] contribute to the trait.<ref>{{cite journal | vauthors = McManus IC, Davison A, Armour JA | title = Multilocus genetic models of handedness closely resemble single-locus models in explaining family data and are compatible with genome-wide association studies | journal = Annals of the New York Academy of Sciences | volume = 1288 | issue = 1 | pages = 48–58 | date = June 2013 | pmid = 23631511 | pmc = 4298034 | doi = 10.1111/nyas.12102 | bibcode = 2013NYASA1288...48M }}</ref>

Brandler et al. performed a [[genome-wide association study]] for a measure of relative hand skill and found that genes involved in the determination of [[left-right asymmetry]] in the body play a key role in handedness.<ref>{{cite journal | vauthors = Brandler WM, Morris AP, Evans DM, Scerri TS, Kemp JP, Timpson NJ, St Pourcain B, Smith GD, Ring SM, Stein J, Monaco AP, Talcott JB, Fisher SE, Webber C, Paracchini S | display-authors = 6 | title = Common variants in left/right asymmetry genes and pathways are associated with relative hand skill | journal = PLOS Genetics | volume = 9 | issue = 9 | pages = e1003751 | date = September 2013 | pmid = 24068947 | pmc = 3772043 | doi = 10.1371/journal.pgen.1003751 | doi-access = free }}</ref> Brandler and [[Silvia Paracchini|Paracchini]] suggest the same mechanisms that determine left-right asymmetry in the body (e.g. [[nodal signaling]] and [[ciliogenesis]]) also play a role in the development of [[brain asymmetry]]
(handedness being a reflection of brain asymmetry for motor function).<ref>{{cite journal | vauthors = Brandler WM, Paracchini S | title = The genetic relationship between handedness and neurodevelopmental disorders | journal = Trends in Molecular Medicine | volume = 20 | issue = 2 | pages = 83–90 | date = February 2014 | pmid = 24275328 | pmc = 3969300 | doi = 10.1016/j.molmed.2013.10.008 }}</ref>

In 2019, Wiberg et al. performed a genome-wide association study and found that handedness was significantly associated with four loci, three of them in genes encoding proteins involved in brain development.<ref>{{cite journal | vauthors = Wiberg A, Ng M, Al Omran Y, Alfaro-Almagro F, McCarthy P, Marchini J, Bennett DL, Smith S, Douaud G, Furniss D | display-authors = 6 | title = Handedness, language areas and neuropsychiatric diseases: insights from brain imaging and genetics | journal = Brain | volume = 142 | issue = 10 | pages = 2938–2947 | date = October 2019 | pmid = 31504236 | pmc = 6763735 | doi = 10.1093/brain/awz257 }}</ref>