High inbreeding in the Faroe Islands does not appear to constitute a risk factor for multiple sclerosis

被引:16
作者
Binzer, S. [2 ,3 ,4 ,6 ]
Imrell, K. [7 ]
Binzer, M. [1 ,5 ]
Kyvik, K. O. [1 ,8 ]
Hillert, J. [7 ]
Stenager, E. [1 ,2 ,3 ,4 ]
机构
[1] Univ Southern Denmark, Inst Reg Hlth Serv Res, Odense, Denmark
[2] MS Clin Southern Jutland, Dept Neurol, Sonderborg, Denmark
[3] MS Clin Southern Jutland, Dept Neurol, Esbjerg, Denmark
[4] MS Clin Southern Jutland, Dept Neurol, Vejle, Denmark
[5] Torshavn Natl Hosp, Torshavn, Faroe Islands, Denmark
[6] Faroe Isl Odense Patient Data Explorat Network OP, Odense, Denmark
[7] Karolinska Inst, Clin Neurosci, Div Neurol, Dept Clin Neurosci, S-10401 Stockholm, Sweden
[8] Odense Univ Hosp, Odense Patient Data Explorat Network OPEN, Odense, Denmark
关键词
Multiple sclerosis; genetics; inbreeding; Faroe Islands; runs of homozygosity; risk factors; ISOLATED POPULATION; SUSCEPTIBILITY; CONSANGUINITY; HOMOZYGOSITY; ASSOCIATION; SHETLAND; ISOLATE; ORKNEY;
D O I
10.1177/1352458514557305
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: Large population-based genome-wide association studies have identified several multiple sclerosis (MS) genetic risk variants, but the existing missing heritability warrants different strategies. Isolated populations offer an alternative way of searching for rare genetic variants and evaluating the possible role of consanguinity in the development of MS. Studies of consanguinity and MS risk have yielded conflicting results. Objectives: In this study we investigated the role of consanguinity on MS risk in the relatively isolated Faroe Islands, which have a presumed high level of inbreeding. Methods: A total of 29 cases and 28 matched controls were genotyped and assessed for inbreeding coefficients, number of runs of homozygosity (ROH) at different lengths and observed number of homozygotes as measures of relatedness. Parametric and non-parametric statistical models were applied. Results: Both cases and controls exhibited considerable relatedness demonstrated by very high inbreeding coefficients, large number of observed homozygotes and many long ROH. However, apart from the number of ROH 2.5 mega base pairs, no significant differences between the two groups were observed. Conclusions: Overall, no significant difference between cases and controls were found, indicating that consanguinity in itself does not appear to be an important risk factor for MS in the population of the Faroe Islands.
引用
收藏
页码:996 / 1002
页数:7
相关论文
共 23 条
[1]   Familial multiple sclerosis: does consanguinity have a role? [J].
Al Jumah, M. ;
Kojan, S. ;
Al Khathaami, A. ;
Al Abdulkaream, I. ;
Al Blawi, M. ;
Jawhary, A. .
MULTIPLE SCLEROSIS JOURNAL, 2011, 17 (04) :487-489
[2]   Highly discrepant proportions of female and male Scandinavian and British Isles ancestry within the isolated population of the Faroe Islands [J].
Als, TD ;
Jorgensen, TH ;
Borglum, AD ;
Petersen, PA ;
Mors, O ;
Wang, AG .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2006, 14 (04) :497-504
[3]   Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis [J].
Beecham, Ashley H. ;
Patsopoulos, Nikolaos A. ;
Xifara, Dionysia K. ;
Davis, Mary F. ;
Kemppinen, Anu ;
Cotsapas, Chris ;
Shah, Tejas S. ;
Spencer, Chris ;
Booth, David ;
Goris, An ;
Oturai, Annette ;
Saarela, Janna ;
Fontaine, Bertrand ;
Hemmer, Bernhard ;
Martin, Claes ;
Zipp, Frauke ;
D'Alfonso, Sandra ;
Martinelli-Boneschi, Filippo ;
Taylor, Bruce ;
Harbo, Hanne F. ;
Kockum, Ingrid ;
Hillert, Jan ;
Olsson, Tomas ;
Ban, Maria ;
Oksenberg, Jorge R. ;
Hintzen, Rogier ;
Barcellos, Lisa F. ;
Agliardi, Cristina ;
Alfredsson, Lars ;
Alizadeh, Mehdi ;
Anderson, Carl ;
Andrews, Robert ;
Sondergaard, Helle Bach ;
Baker, Amie ;
Band, Gavin ;
Baranzini, Sergio E. ;
Barizzone, Nadia ;
Barrett, Jeffrey ;
Bellenguez, Celine ;
Bergamaschi, Laura ;
Bernardinelli, Luisa ;
Berthele, Achim ;
Biberacher, Viola ;
Binder, Thomas M. C. ;
Blackburn, Hannah ;
Bomfim, Izaura L. ;
Brambilla, Paola ;
Broadley, Simon ;
Brochet, Bruno ;
Brundin, Lou .
NATURE GENETICS, 2013, 45 (11) :1353-+
[4]   FAMILIAL CLUSTERING OF MULTIPLE-SCLEROSIS IN A NORTHERN SWEDISH RURAL DISTRICT [J].
BINZER, M ;
FORSGREN, L ;
HOLMGREN, G ;
DRUGGE, U ;
FREDRIKSON, S .
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY, 1994, 57 (04) :497-499
[5]   Multiple sclerosis in a family on the Faroe Islands [J].
Binzer, S. ;
Imrell, K. ;
Binzer, M. ;
Vang, S. ;
Rogvi-Hansen, B. ;
Hillert, J. ;
Stenager, E. .
ACTA NEUROLOGICA SCANDINAVICA, 2010, 121 (01) :16-19
[6]   A cluster of multiple sclerosis cases in Lysvik in the Swedish county of Varmland [J].
Callander, M ;
Landtblom, AM .
ACTA NEUROLOGICA SCANDINAVICA, 2004, 110 (01) :14-22
[7]   Epidemiology of multiple sclerosis in south-western Sardinia [J].
Cocco, Eleonora ;
Sardu, Claudia ;
Massa, Rita ;
Mamusa, Elena ;
Musu, Luigina ;
Ferrigno, Paola ;
Melis, Maurizio ;
Montomoli, Cristina ;
Ferretti, Virginia ;
Coghe, Giancarlo ;
Fenu, Giuseppe ;
Frau, Jessica ;
Lorefice, Lorena ;
Carboni, Nicola ;
Contu, Paolo ;
Marrosu, Maria G. .
MULTIPLE SCLEROSIS JOURNAL, 2011, 17 (11) :1282-1289
[8]   Multiple sclerosis [J].
Compston, Alastair ;
Coles, Alasdair .
LANCET, 2008, 372 (9648) :1502-1517
[9]   Familial clustering of multiple sclerosis in a Dutch genetic isolate [J].
Hoppenbrouwers, I. A. ;
Cortes, L. M. Pardo ;
Aulchenko, Y. S. ;
Sintnicolaas, K. ;
Njajou, O. ;
Snijders, P. J. L. M. ;
Oostra, B. A. ;
van Duijn, C. M. ;
Hintzen, R. Q. .
MULTIPLE SCLEROSIS, 2007, 13 (01) :17-24
[10]   Genome-wide Association Study in a High-Risk Isolate for Multiple Sclerosis Reveals Associated Variants in STAT3 Gene [J].
Jakkula, Eveliina ;
Leppa, Virpi ;
Sulonen, Anna-Maija ;
Varilo, Teppo ;
Kallio, Suvi ;
Kemppinen, Anu ;
Purcell, Shaun ;
Koivisto, Keijo ;
Tienari, Pentti ;
Sumelahti, Maria-Liisa ;
Elovaara, Irina ;
Pirttila, Tuula ;
Reunanen, Mauri ;
Aromaa, Arpo ;
Oturai, Annette Bang ;
Sondergaard, Helle Bach ;
Harbo, Hanne F. ;
Mero, Inger-Lise ;
Gabriel, Stacey B. ;
Mirel, Daniel B. ;
Hauser, Stephen L. ;
Kappos, Ludwig ;
Polman, Chris ;
De Jager, Philip L. ;
Hafler, David A. ;
Daly, Mark J. ;
Palotie, Aarno ;
Saarela, Janna ;
Peltonen, Leena .
AMERICAN JOURNAL OF HUMAN GENETICS, 2010, 86 (02) :285-291