(ii) PROBA ND R A TE FOR M ND
The co-tw ins o f two previously defined index cases, who also died from M ND , were id en tified independently o f their tw in during death certificate processing. This increased the com plete sample to 130 probands and co -tw ins, leaving 91, w hen the probands w ith u ntraceable or in fan t death co-tw ins were rem oved.
T he 91 probands and co-tw ins consisted o f 68 (74.7% ) like-sexed probands and 23 (25.3% ) u n like-sexed probands. The sex distribution among the probands was 50 males and 41 fem ales, giving a ratio o f 1.2:1, and the mean age at death was 63.4 (SD + /- 9 .6 ), age range 37 - 85 years.
(iii) PA R TIC IPA T IN G TWIN PAIRS
Probands w ith Living Co-tw ins: Forty seven of the fifty eight living co-tw ins agreed to be interview ed. O f the rem aining eleven, 2 lived abroad, access to 2 was denied by the GP because o f ill-h ealth (1 x senile dem entia; 1 x psychotic depression), and 7 refused to participate. How ever, of these 11, relatives o f 6 probands supplied some inform ation about the tw in pairs concerned, including probable zygosity. The rem aining 5 pairs consisted o f 2 unlike-sexed pairs; and the zygosity o f the others was obtained from the co -tw in , or their m edical records, via their GP. These G P’s also confirm ed w hether the co-tw ins were presently suffering from MND.
Probands with A dult Death Co-tw ins: Positive contact was made w ith the relatives o f 19 probands w here both twins had died. A ttem pts to contact the others were unsuccessful. The p articipating relatives were again able to recall some inform ation regarding the life-styles of both tw ins, including probable zygosity.
Probands w ith In fan t Death C o-tw ins: A ttem pts were also m ade to contact all the relatives o f the probands w ithin this group. The m ain reason was to establish if any o f these probands cam e from fam ilies w ith FM ND . If possible a sibling was recru ited as a control fo r these probands, because apart from sharing the p re-n a ta l environm ent, siblings are genetically equivalent to dizygotic twins, and if close in age, will have shared the same environm ent as children. This was done to enable a broader cross section o f probands to be sam pled and allow com parison with those whose co -tw in lived through adulthood.
Six siblings were willing to be interview ed as controls. The data obtained from these pairings treated separately at all tim es, but added to the tw in pair data when appropriate. If was
exposure to a particular environm ental factor had produced interesting results, the sibling data was added to see w hether the relationship was enhanced or w eakened. This extra data proved a useful means o f validating the findings as the sample size was relatively small.
R ecruitm ent o f Living Probands and Co-tw ins: D uring this study, details of 7 living probands and 1 who died in 1990 with a living c o -tw in , were sent by neurologists or the M otor N eurone Disease Association. Interview s were carried out w ith these tw ins, but they were not included in the genetic determ ination calculations as they w ere a n on-population sample. The data obtained from the environm ental questionnaire was treated in the same way as the sibling data.
3.2 RESU LTS O F ZY GOSITY V ERIFICATION
A pplying W einberg’s rule to the com plete tw in sample for an approxim ation o f the expected M Z and DZ tw in proportions produces the following:
The proportion of MZ pairs =
86 - 42
= 34.4%
(44 pairs)
128
The proportion of DZ pairs =
2 x 42
= 65.6%
(84 pairs)
128
Out o f the 88 like-sexed probands id entified, obviously the zygosity o f the like-sexed twins among the untraceable (5) and in fan t death (15) c o -tw in pairs, and the adult death pairs for who no inform ation was available (10), was not discernible. Among the rem aining 58 like- sexed probands and co-tw ins, zygosity questionnaire data was available for 55, and analysis iden tified 25 M Z and 30 DZ probands and co-tw ins. The twins w ere classified M Z if they scored near m axim um points on the questionnaire, along w ith a positive response to the ’like two peas in a pod’ question. All other scores were classified DZ. A ccording to the inform ation obtained from the G P’s o f the n o n -p articip atin g living c o -tw in pairs this increased the proportions to 26 M Z and 32 DZ probands and co-tw ins. An equivalent group of unlike-sexed probands and co-tw ins was included in the genetic calculations (19 pairs), giving a total of 77 probands and co-tw ins (figure 4).