TY - JOUR

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

AU - Kolte, Astrid Marie

AU - Nielsen, Henriette Svarre

AU - Moltke, Ida

AU - Degn, B.

AU - Pedersen, B.

AU - Sunde, L.

AU - Nielsen, Finn Cilius

AU - Christiansen, Ole B

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 is comprised of two parts: 1) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and 2) a genetic part presenting data from a genome-wide linkage study of 38 affected sib-pairs with IRM. All IRM patients (probands) had experienced =3 miscarriages and affected siblings =2 miscarriages. The sib-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 sib-pairs. Maximum LOD scores were identified in four occurrences: for rs10514716 (3p14.2) when analysing sister-pairs only; for rs10511668 (9p22.1) and rs341048 (11q13.4) when only analysing families where the probands have had =4 miscarriages; and for rs10485275 (6q16.3) when analyzing one sib-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 sib-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 is comprised of two parts: 1) an epidemiological part, in which we introduce data on the frequency of miscarriage among 268 siblings of 244 patients with IRM and 2) a genetic part presenting data from a genome-wide linkage study of 38 affected sib-pairs with IRM. All IRM patients (probands) had experienced =3 miscarriages and affected siblings =2 miscarriages. The sib-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 sib-pairs. Maximum LOD scores were identified in four occurrences: for rs10514716 (3p14.2) when analysing sister-pairs only; for rs10511668 (9p22.1) and rs341048 (11q13.4) when only analysing families where the probands have had =4 miscarriages; and for rs10485275 (6q16.3) when analyzing one sib-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 sib-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.

U2 - 10.1093/molehr/gar003

DO - 10.1093/molehr/gar003

M3 - Journal article

C2 - 21257601

VL - 17

SP - 379

EP - 385

JO - Molecular Human Reproduction

JF - Molecular Human Reproduction

SN - 1360-9947

IS - 6

ER -