A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage

Astrid Marie Kolte; H S Nielsen; Ida Moltke; B Degn; Bjørn Pedersen; Lone E. M. Sunde; F C Nielsen; Ole Bjarne Christiansen

doi:10.1093/molehr/gar003

A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage

Astrid Marie Kolte, H S Nielsen, Ida Moltke, B Degn, Bjørn Pedersen, Lone E. M. Sunde, F C Nielsen, Ole Bjarne Christiansen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Conference abstract in journal › Research › peer-review

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Abstract

Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and (ii) a genetic part presenting data from a genome-wide linkage study of 38 affected sibling pairs with IRM. All IRM patients (probands) had experienced three or more miscarriages and affected siblings two or more miscarriages. The sibling pairs were genotyped by the Affymetrix GeneChip 50K XbaI platform and non-parametric linkage analysis was performed via the software package Merlin. We find that siblings of IRM patients exhibit a higher frequency of miscarriage than population controls regardless of age at the time of pregnancy. We identify chromosomal regions with LOD scores between 2.5 and 3.0 in subgroups of affected sibling pairs. Maximum LOD scores were identified in four occurrences: for rs10514716 (3p14.2) when analyzing sister-pairs only; for rs10511668 (9p22.1) and rs341048 (11q13.4) when only analyzing families where the probands have had four or more miscarriages; and for rs10485275 (6q16.3) when analyzing one sibling pair from each family only. We identify no founder mutations. Concluding, our results imply that IRM patients and their siblings share factors which increase the risk of miscarriage. In this first genome-wide linkage study of affected sibling pairs with IRM, we identify regions on chromosomes 3, 6, 9 and 11 which warrant further investigation in order to elucidate their putative roles in the genesis of IRM.

Original language	English
Journal	Journal of Reproductive Immunology
Volume	90
Issue	2
Pages (from-to)	147
Number of pages	1
ISSN	0165-0378
DOIs	https://doi.org/10.1093/molehr/gar003
Publication status	Published - 2011
Event	9th Congress of the European Association of Reproductive Immunology - København, Denmark Duration: 23 Aug 2011 → 27 Aug 2011

Conference

Conference	9th Congress of the European Association of Reproductive Immunology
Country/Territory	Denmark
City	København
Period	23/08/2011 → 27/08/2011

Keywords

Abortion, Habitual
Adolescent
Adult
Chromosome Mapping
Denmark
Female
Genetic Predisposition to Disease
Genetic Testing
Genome, Human
Genome-Wide Association Study
Genotype
Humans
Lod Score
Oligonucleotide Array Sequence Analysis
Pregnancy
Risk Factors
Siblings
Software

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10.1093/molehr/gar003

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@article{4f82d7c96c4f43e29c6b00be29b53b14,

title = "A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage",

abstract = "Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and (ii) a genetic part presenting data from a genome-wide linkage study of 38 affected sibling pairs with IRM. All IRM patients (probands) had experienced three or more miscarriages and affected siblings two or more miscarriages. The sibling pairs were genotyped by the Affymetrix GeneChip 50K XbaI platform and non-parametric linkage analysis was performed via the software package Merlin. We find that siblings of IRM patients exhibit a higher frequency of miscarriage than population controls regardless of age at the time of pregnancy. We identify chromosomal regions with LOD scores between 2.5 and 3.0 in subgroups of affected sibling pairs. Maximum LOD scores were identified in four occurrences: for rs10514716 (3p14.2) when analyzing sister-pairs only; for rs10511668 (9p22.1) and rs341048 (11q13.4) when only analyzing families where the probands have had four or more miscarriages; and for rs10485275 (6q16.3) when analyzing one sibling pair from each family only. We identify no founder mutations. Concluding, our results imply that IRM patients and their siblings share factors which increase the risk of miscarriage. In this first genome-wide linkage study of affected sibling pairs with IRM, we identify regions on chromosomes 3, 6, 9 and 11 which warrant further investigation in order to elucidate their putative roles in the genesis of IRM.",

keywords = "Abortion, Habitual, Adolescent, Adult, Chromosome Mapping, Denmark, Female, Genetic Predisposition to Disease, Genetic Testing, Genome, Human, Genome-Wide Association Study, Genotype, Humans, Lod Score, Oligonucleotide Array Sequence Analysis, Pregnancy, Risk Factors, Siblings, Software",

author = "Kolte, {Astrid Marie} and Nielsen, {H S} and Ida Moltke and B Degn and Bj{\o}rn Pedersen and Sunde, {Lone E. M.} and Nielsen, {F C} and Christiansen, {Ole Bjarne}",

year = "2011",

doi = "10.1093/molehr/gar003",

language = "English",

volume = "90",

pages = "147",

journal = "Journal of Reproductive Immunology",

issn = "0165-0378",

publisher = "Elsevier Ireland Ltd",

number = "2",

note = "9th Congress of the European Association of Reproductive Immunology ; Conference date: 23-08-2011 Through 27-08-2011",

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A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage. / Kolte, Astrid Marie; Nielsen, H S; Moltke, Ida et al.
In: Journal of Reproductive Immunology, Vol. 90, No. 2, 2011, p. 147.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Conference abstract in journal › Research › peer-review

TY - ABST

T1 - A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage

AU - Kolte, Astrid Marie

AU - Nielsen, H S

AU - Moltke, Ida

AU - Degn, B

AU - Pedersen, Bjørn

AU - Sunde, Lone E. M.

AU - Nielsen, F C

AU - Christiansen, Ole Bjarne

PY - 2011

Y1 - 2011

N2 - Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and (ii) a genetic part presenting data from a genome-wide linkage study of 38 affected sibling pairs with IRM. All IRM patients (probands) had experienced three or more miscarriages and affected siblings two or more miscarriages. The sibling pairs were genotyped by the Affymetrix GeneChip 50K XbaI platform and non-parametric linkage analysis was performed via the software package Merlin. We find that siblings of IRM patients exhibit a higher frequency of miscarriage than population controls regardless of age at the time of pregnancy. We identify chromosomal regions with LOD scores between 2.5 and 3.0 in subgroups of affected sibling pairs. Maximum LOD scores were identified in four occurrences: for rs10514716 (3p14.2) when analyzing sister-pairs only; for rs10511668 (9p22.1) and rs341048 (11q13.4) when only analyzing families where the probands have had four or more miscarriages; and for rs10485275 (6q16.3) when analyzing one sibling pair from each family only. We identify no founder mutations. Concluding, our results imply that IRM patients and their siblings share factors which increase the risk of miscarriage. In this first genome-wide linkage study of affected sibling pairs with IRM, we identify regions on chromosomes 3, 6, 9 and 11 which warrant further investigation in order to elucidate their putative roles in the genesis of IRM.

AB - Previously, siblings of patients with idiopathic recurrent miscarriage (IRM) have been shown to have a higher risk of miscarriage. This study comprises two parts: (i) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and (ii) a genetic part presenting data from a genome-wide linkage study of 38 affected sibling pairs with IRM. All IRM patients (probands) had experienced three or more miscarriages and affected siblings two or more miscarriages. The sibling pairs were genotyped by the Affymetrix GeneChip 50K XbaI platform and non-parametric linkage analysis was performed via the software package Merlin. We find that siblings of IRM patients exhibit a higher frequency of miscarriage than population controls regardless of age at the time of pregnancy. We identify chromosomal regions with LOD scores between 2.5 and 3.0 in subgroups of affected sibling pairs. Maximum LOD scores were identified in four occurrences: for rs10514716 (3p14.2) when analyzing sister-pairs only; for rs10511668 (9p22.1) and rs341048 (11q13.4) when only analyzing families where the probands have had four or more miscarriages; and for rs10485275 (6q16.3) when analyzing one sibling pair from each family only. We identify no founder mutations. Concluding, our results imply that IRM patients and their siblings share factors which increase the risk of miscarriage. In this first genome-wide linkage study of affected sibling pairs with IRM, we identify regions on chromosomes 3, 6, 9 and 11 which warrant further investigation in order to elucidate their putative roles in the genesis of IRM.

KW - Abortion, Habitual

KW - Adolescent

KW - Adult

KW - Chromosome Mapping

KW - Denmark

KW - Female

KW - Genetic Predisposition to Disease

KW - Genetic Testing

KW - Genome, Human

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Lod Score

KW - Oligonucleotide Array Sequence Analysis

KW - Pregnancy

KW - Risk Factors

KW - Siblings

KW - Software

U2 - 10.1093/molehr/gar003

DO - 10.1093/molehr/gar003

M3 - Conference abstract in journal

C2 - 21257601

SN - 0165-0378

VL - 90

SP - 147

JO - Journal of Reproductive Immunology

JF - Journal of Reproductive Immunology

IS - 2

T2 - 9th Congress of the European Association of Reproductive Immunology

Y2 - 23 August 2011 through 27 August 2011

ER -

A genome-wide scan in affected sibling pairs with idiopathic recurrent miscarriage suggests genetic linkage

Abstract

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Keywords

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